Blueprint
FORM 6-K
SECURITIES
AND EXCHANGE COMMISSION
Washington,
D.C. 20549
Report
of Foreign Issuer
Pursuant
to Rule 13a-16 or 15d-16 of
the
Securities Exchange Act of 1934
For the
month of November
2017
Commission
File Number: 001-11960
AstraZeneca PLC
1
Francis Crick Avenue
Cambridge
Biomedical Campus
Cambridge
CB2 0AA
United
Kingdom
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by check mark whether the registrant files or will file annual
reports under cover of Form 20-F or Form 40-F.
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by check mark whether the registrant by furnishing the information
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to the Commission pursuant to Rule 12g3-2(b) under the Securities
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assigned to the Registrant in connection with Rule 12g3-2(b):
82-_____________
AstraZeneca PLC
9
November 2017 07:00
Year-To-Date and Q3 2017 Results
An improved sales performance as the pipeline-driven transformation
gathered pace
Financial Summary
|
YTD 2017
|
Q3 2017
|
$m
|
% change
|
$m
|
% change
|
|
Actual
|
CER1
|
Actual
|
CER
|
Total
Revenue
|
16,688
|
(4)
|
(3)
|
6,232
|
9
|
10
|
Product Sales
|
14,665
|
(9)
|
(8)
|
4,882
|
(3)
|
(2)
|
Externalisation Revenue
|
2,023
|
49
|
50
|
1,350
|
n/m
|
n/m
|
|
|
|
|
|
|
|
Reported
Operating Profit
|
2,991
|
26
|
16
|
1,149
|
12
|
9
|
Core
Operating Profit2
|
5,068
|
8
|
5
|
1,853
|
9
|
9
|
|
|
|
|
|
|
|
Reported
Earnings Per Share (EPS)
|
$1.34
|
3
|
(4)
|
$0.54
|
(32)
|
(33)
|
Core
EPS
|
$2.98
|
(4)
|
(7)
|
$1.12
|
(15)
|
(17)
|
The difference in growth rates between Operating Profit and EPS
included the impact of a one-off tax benefit in Q3
2016.
Financial Highlights
●
Receding impact from losses of exclusivity: Product
Sales declined by 3% (2% at CER) in the quarter
● Externalisation Revenue: $2,023m, including $997m
received in the quarter from the MSD3 collaboration
●
Cost discipline continued:
●
Reported R&D costs declined by 3% (1% at
CER) to $4,206m; Core R&D costs declined by 5% (2% at CER) to
$3,956m
●
Reported SG&A costs declined by 11% (9% at
CER) to $7,155m; Core SG&A costs declined by 7% (5% at CER) to
$5,678m
●
The Company now anticipates a 2017 Core EPS performance
towards the favourable end of the guidance range of a low to mid
teens percentage decline
Commercial Highlights
The
Growth Platforms grew by 3% (4% at CER) and represented 66% of
Total Revenue:
●
Emerging Markets: 5% growth (7% at CER). China
sales in the quarter increased by 12% (14% at CER)
●
Respiratory: 5% decline (3% at CER).
Symbicort faced continued
pressures in the US
●
New CVMD4: 5% growth. Brilinta sales up by 29% (31% at CER); Farxiga sales up by 24%
●
Japan: 3% growth (5% at CER). Underpinned by
the growth of Tagrisso,
Symbicort and Nexium
●
New Oncology5: 96% growth (97% at CER). An encouraging
performance by Tagrisso; Lynparza US sales up by 9% in the
quarter
Achieving Scientific Leadership
The
table below highlights the development of the late-stage pipeline
since 27 July 2017:
Regulatory
Approvals
|
Faslodex - breast cancer (1st
line) (US)
Lynparza - ovarian cancer (2nd
line, 4th line/tablets) (US)
Calquence (acalabrutinib) -
blood cancer (mantle cell lymphoma (MCL), 2nd line)
(US)
Brilinta - prior myocardial
infarction (MI) (CN)
Farxiga + Bydureon - type-2 diabetes (US, EU)
Bydureon BCise (autoinjector) - type-2 diabetes
(US)
Symbicort - chronic obstructive
pulmonary disease (COPD) exacerbations (US)
|
Regulatory
Submission Acceptances
|
Lynparza - breast cancer (US,
JP) (Priority Reviews)
Imfinzi - locally-advanced,
unresectable lung cancer (US/Priority Review, EU,
JP)
Bydureon BCise - type-2 diabetes (EU)
|
Major
Phase
III
Data
Readouts
|
moxetumomab
pasudotox - leukaemia (met
primary endpoint)
Duaklir - COPD (met primary endpoint)
tralokinumab
- severe, uncontrolled asthma (did not meet primary
endpoints)
|
Other
Major Developments
|
Tagrisso - lung cancer (1st line): Breakthrough Therapy
Designation (US)
Imfinzi - locally-advanced, unresectable lung cancer: Breakthrough
Therapy Designation (US)
|
Pascal Soriot, Chief Executive Officer, commenting on the results
said:
"Our
financial performance in the quarter was in line with expectations,
reflecting good commercial execution, including strong growth in
Emerging Markets with standout sales in China.
It was,
however, the raft of news flow and approvals that was most notable.
In particular, the positive developments for Tagrisso and Imfinzi in lung cancer and benralizumab
and tezepelumab in asthma offset the disappointment of the first
readout from the MYSTIC trial. The Accelerated Approval for
Calquence in the treatment
of an aggressive form of blood cancer was an important milestone
for a medicine that will be the cornerstone of our presence in
blood cancers. Further, the new strategic collaboration with MSD
offers significant opportunities to maximise the potential of
Lynparza.
This
impressive momentum is set to continue with regulatory and data
milestones that have the potential to show how our science-led
strategy and pipeline-driven transformation are delivering for
patients and shareholders."
FY 2017 Guidance: Updated
The
Company provides guidance on Total Revenue and Core EPS only and
today refines the guidance for Core EPS. This refinement primarily
reflects the impact of the aforementioned MSD collaboration, for
which the accounting treatment was finalised in the
quarter.
All
commentary in this section is at CER.
|
Updated Guidance
|
Prior Guidance
|
Total Revenue
|
A low
to mid single-digit percentage decline
|
A low
to mid single-digit percentage decline
|
Core EPS
|
Towards
the favourable end of a low to mid teens percentage
decline*
|
A low
to mid teens percentage decline
|
*The Core EPS guidance anticipates a normalised effective Core tax
rate in FY 2017 of 17-19% (FY 2016: 11%).
Guidance is subject to base-case assumptions of the progression of
the pipeline and the extensive level of news flow listed on the
following page. Variations in performance between quarters can be
expected, with year-on-year Product Sales comparisons easing in the
second half of the year, following the entry of multiple
Crestor
generic medicines in the US market in
July 2016.
The Company presents Core EPS guidance only at CER. It is unable to
provide guidance on a Reported/GAAP6
basis because the Company cannot
reliably forecast material elements of the Reported/GAAP result,
including the fair value adjustments arising on acquisition-related
liabilities, intangible asset impairment charges and legal
settlement provisions. Please refer to the section 'Cautionary
Statements Regarding Forward-Looking Statements' at the end of this
announcement.
In addition to the unchanged guidance above, the Company also
provides unchanged indications in other areas of the Income
Statement. The sum of Externalisation Revenue and Other Operating
Income and Expense in
FY 2017 is anticipated to be ahead of that in FY 2016. Sustainable
and ongoing income7 is expected to increase further as a proportion of
total Externalisation Revenue in FY 2017 (FY 2016: 21%). Core
R&D costs are expected to be broadly in line with those in FY
2016 and the Company anticipates a further reduction in Core
SG&A costs in FY 2017, reflecting the evolving shape of the
business. A full explanation is listed in the Operating &
Financial Review.
FY 2017 Currency Impact
Based
only on average exchange rates in the
first nine months of 2017 (year to date, YTD 2017) and the
Company's published currency sensitivities, the Company continues
to expect a low single-digit percentage adverse impact from
currency movements on Total Revenue and a minimal impact on Core
EPS. Further details on currency sensitivities are contained within
the Operating and Financial Review.
Notes
1.
Constant exchange rates. These are non-GAAP measures because they
remove the effects of currency movements from Reported
results.
2. Core
financial measures. These are non-GAAP measures because, unlike
Reported performance, they cannot be derived directly from the
information in the Group Financial Statements. See the Operating
and Financial Review for a definition of Core financial measures
and a reconciliation of Core to Reported financial
measures.
3.
Merck & Co., Inc., Kenilworth, NJ, US (known as MSD outside the
US and Canada)
4. New
Cardiovascular and Metabolic Diseases, incorporating Brilinta and Diabetes.
5. New
Oncology, comprising Lynparza, Tagrisso, Iressa (US), Imfinzi and, in due course,
Calquence.
6.
Generally Accepted Accounting Principles.
7.
Sustainable and ongoing income is defined as Externalisation
Revenue, excluding initial revenue.
All
growth rates are shown at actual exchange rates, unless stated
otherwise. Only one rate of growth is shown if the actual and
constant exchange rates of growth are identical. All commentary in
this announcement refers to the performance in the year to date,
unless stated otherwise.
Pipeline: Forthcoming Major News Flow
Innovation
is critical to addressing unmet patient needs and is at the heart
of the Company's growth strategy. The focus on research and
development is designed to yield strong results from the
pipeline.
Q4
2017
|
Tagrisso - lung cancer (1st
line): Regulatory submission
benralizumab - severe, uncontrolled asthma: Regulatory decision
(US)
|
H1
2018
|
Lynparza - ovarian cancer (2nd line): Regulatory decision
(EU, JP)
Lynparza - ovarian cancer (1st line): Data
readout
Lynparza - breast cancer: Regulatory decision (US),
regulatory submission (EU)
Imfinzi - lung cancer (PACIFIC): Regulatory decision
(US)
Imfinzi +/- treme - lung cancer (ARCTIC): Data readout,
regulatory submission
Imfinzi +/- treme - lung cancer (MYSTIC): Data readout
(final overall survival)
Imfinzi +/- treme - head
& neck cancer (KESTREL): Data
readout
Imfinzi +/- treme - head & neck cancer (EAGLE): Data
readout
moxetumomab
pasudotox - leukaemia:
Regulatory submission
selumetinib
- thyroid cancer: Data readout, regulatory submission
Bevespi - COPD: Regulatory
submission (JP)
Duaklir - COPD: Regulatory submission (US)
benralizumab
- severe, uncontrolled asthma: Regulatory decision (EU,
JP)
PT010 -
COPD: Data readout
|
H2
2018
|
Lynparza - breast cancer: Regulatory decision
(JP)
Lynparza - ovarian cancer (1st line): Regulatory
submission
Imfinzi - lung cancer (PACIFIC): Regulatory decision (EU,
JP)
Imfinzi +/- treme - lung cancer
(MYSTIC): Regulatory submission
Imfinzi + treme - lung cancer (NEPTUNE): Data readout,
regulatory submission
Imfinzi +/- treme - head
& neck cancer (KESTREL):
Regulatory submission
Imfinzi +/- treme - head & neck cancer (EAGLE):
Regulatory submission
Farxiga - type-2 diabetes
(DECLARE): Data readout
Bydureon BCise - type-2 diabetes: Regulatory decision
(EU)
roxadustat
- anaemia: Regulatory
submission (US)
Bevespi - COPD: Regulatory
decision (EU)
benralizumab - COPD: Data readout, regulatory
submission
PT010 -
COPD: Regulatory submission (JP)
anifrolumab
- lupus: Data
readout
|
The term 'data readout' in this section refers to Phase III data
readouts.
Conference Call
A
conference call and webcast for investors and analysts, hosted by
management, will begin at 12:00 UK time today. Details can be
accessed via astrazeneca.com/investors.
Reporting Calendar
The
Company intends to publish its full-year and fourth-quarter
financial results on 2 February 2018.
About AstraZeneca
AstraZeneca is a global, science-led biopharmaceutical company that
focuses on the discovery, development and commercialisation of
prescription medicines, primarily for the treatment of diseases in
three main therapy areas - Oncology, CVMD and Respiratory. The
Company also is selectively active in the areas of autoimmunity,
neuroscience and infection. AstraZeneca operates in over 100
countries and its innovative medicines are used by millions of
patients worldwide.
For more information, please visit www.astrazeneca.com and
follow us on Twitter @AstraZeneca.
Media Relations
|
|
|
Esra
Erkal-Paler
|
UK/Global
|
+44 203
749 5638
|
Rob
Skelding
|
UK/Global
|
+44 203
749 5821
|
Karen
Birmingham
|
UK/Global
|
+44 203
749 5634
|
Matt
Kent
|
UK/Global
|
+44 203
749 5906
|
Gonzalo
Viña
|
UK/Global
|
+44 203
749 5916
|
Jacob
Lund
|
Sweden
|
+46
8 553 260 20
|
Michele
Meixell
|
US
|
+1 302
885 2677
|
|
|
|
Investor Relations
|
|
|
Thomas
Kudsk Larsen
|
|
+44 203
749 5712
|
Craig
Marks
|
Finance;
Fixed Income; M&A
|
+44
7881 615 764
|
Henry
Wheeler
|
Oncology
|
+44 203
749 5797
|
Mitchell
Chan
|
Oncology;
Other
|
+1 240
477 3771
|
Christer
Gruvris
|
Brilinta; Diabetes
|
+44 203
749 5716
|
Nick
Stone
|
Respiratory;
Renal
|
+44 203
749 5711
|
US toll
free
|
|
+1 866
381 7277
|
Operating
and Financial Review
_______________________________________________________________________________________
All
narrative on growth and results in this section is based on actual
exchange rates, unless stated otherwise. Financial figures are in
US$ millions ($m). The performance shown in this announcement
covers the nine and three-month periods to 30 September 2017 (the
year to date (YTD 2017) or the quarter (Q3 2017), respectively)
compared to the nine and three-month periods to 30 September 2016
(YTD 2016 and Q3 2016, respectively). All commentary in the
Operating and Financial Review relates to the year to date, unless
stated otherwise. Core financial measures, EBITDA and Net Debt are
non-GAAP financial measures because they cannot be derived directly
from the Group Condensed Consolidated Financial Statements.
Management believes that these
non-GAAP financial measures, when provided in combination with
Reported results, will provide investors with helpful supplementary
information to better understand the financial performance and
position of the Company on a comparable basis from period to
period. These non-GAAP financial measures are not a
substitute for, or superior to, financial measures prepared in
accordance with GAAP. Core financial measures are adjusted to
exclude certain significant items, such as:
●
Amortisation and impairment of intangible
assets, including impairment reversals but excluding any charges
relating to IT assets
●
Charges and provisions related to global
restructuring programmes (this will include such charges that
relate to the impact of global restructuring programmes on
capitalised IT assets)
●
Other specified items, principally comprising
legal settlements and acquisition-related costs, which include fair
value adjustments and the imputed finance charge relating to
contingent consideration on business combinations
Details on the nature of Core financial measures are provided on
page 64 of the Annual Report
and Form 20-F
Information 2016. Reference should be made to the reconciliation of
Core to Reported financial information included therein and in the
Reconciliation of Reported to Core Financial Measures table
included in the Financial
Performance section of this announcement.
EBITDA
is defined as Reported Profit Before Tax after adding back Net
Finance Expense, Joint Ventures and Associates and charges for
depreciation, amortisation and impairment. Reference should be made
to the Reconciliation of Reported Profit Before Tax to EBITDA
included in the Financial Performance section of this
announcement.
Net
Debt is defined as interest-bearing loans and borrowings net of
cash and cash equivalents, other investments and net derivative
financial instruments. Reference should be made to the
Reconciliation of Interest-Bearing Loans and Borrowings to Net Debt
included in the Cash Flow and Balance Sheet section of this
announcement.
The
Company strongly encourages readers not to rely on any single
financial measure, but to review AstraZeneca's financial
statements, including the notes thereto, and other publicly-filed
Company reports, carefully and in their entirety.
Total Revenue
|
YTD 2017
|
Q3 2017
|
$m
|
% change
|
$m
|
% change
|
Actual
|
CER
|
Actual
|
CER
|
Total
Revenue
|
16,688
|
(4)
|
(3)
|
6,232
|
9
|
10
|
|
|
|
|
|
|
|
Product Sales
|
14,665
|
(9)
|
(8)
|
4,882
|
(3)
|
(2)
|
Externalisation Revenue
|
2,023
|
49
|
50
|
1,350
|
n/m
|
n/m
|
Product Sales
The
receding effects of the Crestor and Seroquel XR losses of exclusivity in
the US impacted Product Sales in the year to date. Global Product
Sales declined by 9% (8% at CER) from $16,059m to $14,665m. Of the
$1,394m difference, $999m was represented by a 36% decline (35% at
CER) in Crestor sales;
$393m was represented by a 64% decline in Seroquel XR sales.
Emerging Markets
sales grew by 5% (7% at CER) to $4,519m; Emerging Markets
represented AstraZeneca's largest sales region in the year to date.
China sales increased by 6% (10% at CER) to $2,142m in the year to
date. In the quarter, China sales increased by 12% (14% at CER) to
$723m, reflecting a strong underlying performance. US sales
declined by 23% to $4,399m and were, alongside the effects of the
Crestor and Seroquel XR losses of exclusivity, also
impacted by the sales of Symbicort, which declined by 15% to
$811m. Product Sales in Europe declined by 7% (6% at CER) to
$3,460m.
Representing 66% of
Total Revenue, the Growth Platforms grew by 3% (4% at CER) to
$11,055m:
|
YTD 2017
|
Q3 2017
|
$m
|
% change
|
$m
|
% change
|
|
Actual
|
CER
|
Actual
|
CER
|
Emerging Markets
|
4,519
|
5
|
7
|
1,515
|
9
|
10
|
Respiratory
|
3,372
|
(5)
|
(3)
|
1,092
|
(2)
|
(2)
|
New
CVMD
|
2,543
|
5
|
5
|
873
|
7
|
7
|
Japan
|
1,645
|
3
|
5
|
578
|
(3)
|
4
|
New
Oncology
|
876
|
96
|
97
|
339
|
72
|
73
|
|
|
|
|
|
|
|
Total*
|
11,055
|
3
|
4
|
3,760
|
5
|
6
|
*Total Product Sales for Growth Platforms are adjusted to remove
duplication on a medicine and regional basis.
Externalisation Revenue
Where
AstraZeneca retains a significant ongoing interest in medicines or
potential new medicines, income arising from externalisation
agreements is reported as Externalisation Revenue in the Company's
financial statements.
A
breakdown of Externalisation Revenue in the year to date is shown
below:
Medicine
|
Partner
|
Region
|
$m
|
Lynparza &
selumetinib
|
MSD
-
initial revenue
|
Global
|
997
|
Zoladex
|
TerSera
Therapeutics LLC (TerSera)- initial revenue
|
US and
Canada
|
250
|
anaesthetics
|
Aspen
Global, Inc. (Aspen)
-
milestone revenue
|
Global
(excl.US)
|
150
|
Siliq
|
Valeant
Pharmaceuticals International, Inc. (Valeant)
-
milestone revenue
|
US
|
130
|
MEDI8897
|
Sanofi
Pasteur, Inc. (Sanofi Pasteur)
-
initial revenue
|
Global
|
127
|
Tudorza/Duaklir
|
Circassia
Pharmaceuticals plc (Circassia)
-
initial revenue
|
US
|
64
|
lanabecestat
|
Eli
Lilly and Company (Lilly)
-
milestone revenue
|
Global
|
50
|
MEDI1341
|
Takeda
Pharmaceutical Company Limited (Takeda)
-
initial revenue
|
Global
|
50
|
Other
|
|
|
205
|
|
|
|
|
Total
|
|
|
2,023
|
The
following table illustrates the level of sustainable and ongoing
income within the total of Externalisation Revenue. The Company
anticipates that sustainable and ongoing income will grow as a
proportion of Externalisation Revenue over time.
|
YTD 2017
|
Q3 2017
|
|
$m
|
% of total
|
% change
|
$m
|
% of total
|
% change
|
Actual
|
CER
|
Actual
|
CER
|
Royalties
|
100
|
5
|
22
|
25
|
31
|
2
|
14
|
57
|
|
|
|
|
|
|
|
|
|
Milestones/Other
|
431
|
21
|
104
|
109
|
272
|
20
|
n/m
|
n/m
|
|
|
|
|
|
|
|
|
|
Total Sustainable and Ongoing Externalisation Revenue
|
531
|
26
|
81
|
85
|
303
|
22
|
n/m
|
n/m
|
|
|
|
|
|
|
|
|
|
Initial Revenue
|
1,492
|
74
|
40
|
39
|
1,047
|
78
|
63
|
60
|
|
|
|
|
|
|
|
|
|
Total Externalisation Revenue
|
2,023
|
100
|
49
|
49
|
1,350
|
100
|
n/m
|
n/m
|
A
number of AstraZeneca medicines were externalised or disposed after
30 September 2016, thus adversely impacting the overall
year-on-year Product Sales performance in the year to
date:
Medicine
|
Region
|
Completion
|
Product Sales in
Impacted Regions
|
YTD 2016
|
YTD 2017*
|
Difference
|
$m
|
$m
|
$m
|
Toprol-XL
|
US
|
October 2016
|
81
|
34
|
(47)
|
Bydureon/Byetta
|
China
|
October 2016
|
9
|
-
|
(9)
|
antibiotics
|
Global
(excl. US)
|
December 2016
|
143
|
28
|
(115)
|
Zoladex
|
US and
Canada
|
March 2017
|
50
|
24
|
(26)
|
Seloken
|
Europe
|
June 2017
|
67
|
48
|
(19)
|
Zomig
|
Global
(excl. Japan)
|
June 2017
|
56
|
45
|
(11)
|
|
|
|
|
|
|
Total
|
|
|
406
|
179
|
(227)
|
Proportion of YTD 2017 Product Sales
|
|
|
|
|
-2%
|
*YTD 2017 Product Sales here comprise sales made to partners under
manufacturing and supply agreements.
Examples
of sustainable and ongoing income, as part of Externalisation
Revenue, are shown below:
Announcement
|
Medicine
|
Partner
|
Region
|
Externalisation Revenue
|
July 2017
|
Lynparza
|
MSD
|
Global
|
●
Initial $1.0bn revenue
●
Up to $0.75bn for certain licence
options
●
Up to $6.15bn in regulatory and sales
milestones
|
March 2017
|
MEDI8897
|
Sanofi
Pasteur
|
Global
|
●
Initial €120m revenue
●
Up to €495m in sales and
development-related milestones
|
February 2017
|
Zoladex
|
TerSera
|
US and
Canada
|
●
Initial $250m revenue
●
Up to $70m in sales-related
milestones
●
Mid-teen percentage royalties on
sales
|
October 2016
|
Toprol-XL
|
Aralez
Pharmaceuticals Inc.
|
US
|
●
Initial $175m revenue
●
Up to $48m milestone and sales-related
revenue
●
Mid-teen percentage royalties on
sales
|
July 2016
|
tralokinumab - atopic dermatitis
|
LEO
Pharma A/S
(LEO
Pharma)
|
Global
|
●
Initial $115m revenue
●
Up to $1bn in commercially-related
milestones
●
Up to mid-teen tiered percentage royalties on
sales
|
September 2015
|
Siliq
|
Valeant
|
Global,
later
amended
to US
|
●
Initial $100m revenue
●
Pre-launch milestone of $130m
●
Sales-related royalties up to
$175m
●
Profit sharing
|
March 2015
|
Movantik
|
Daiichi
Sankyo Company, Ltd
(Daiichi
Sankyo)
|
US
|
●
Initial $200m revenue
●
Up to $625m in sales-related
revenue
|
Product Sales
_____________________________________________________________________________________
The
performance of key medicines is shown below, with a geographical
split shown in Note 6 and 7.
Therapy Area
|
Medicine
|
YTD 2017
|
Q3 2017
|
$m
|
% of total*
|
% change
|
$m
|
% of total
|
% change
|
Actual
|
CER
|
Actual
|
CER
|
Oncology
|
Tagrisso
|
651
|
4
|
136
|
138
|
248
|
5
|
86
|
89
|
Iressa
|
398
|
3
|
1
|
2
|
137
|
3
|
10
|
10
|
Lynparza
|
197
|
1
|
26
|
26
|
81
|
2
|
40
|
36
|
Imfinzi
|
1
|
-
|
n/m
|
n/m
|
-
|
-
|
-
|
-
|
Legacy:
|
|
|
|
|
|
|
|
|
Faslodex
|
703
|
5
|
16
|
16
|
241
|
5
|
16
|
16
|
Zoladex
|
548
|
4
|
(6)
|
(5)
|
185
|
4
|
(7)
|
(6)
|
Casodex
|
161
|
1
|
(14)
|
(12)
|
51
|
1
|
(18)
|
(16)
|
Arimidex
|
160
|
1
|
(9)
|
(6)
|
54
|
1
|
(4)
|
(2)
|
Others
|
85
|
1
|
13
|
16
|
29
|
1
|
7
|
15
|
Total Oncology
|
2,904
|
20
|
18
|
19
|
1,026
|
21
|
18
|
19
|
CVMD
|
Brilinta
|
780
|
5
|
29
|
31
|
284
|
6
|
37
|
36
|
Farxiga
|
742
|
5
|
24
|
24
|
285
|
6
|
30
|
29
|
Onglyza
|
431
|
3
|
(25)
|
(25)
|
127
|
3
|
(25)
|
(25)
|
Bydureon
|
427
|
3
|
(2)
|
(2)
|
128
|
3
|
(12)
|
(12)
|
Byetta
|
128
|
1
|
(36)
|
(35)
|
39
|
1
|
(36)
|
(36)
|
Symlin
|
35
|
-
|
30
|
30
|
10
|
-
|
(9)
|
(9)
|
Legacy:
|
|
|
|
|
|
|
|
|
Crestor
|
1,771
|
12
|
(36)
|
(35)
|
580
|
12
|
(16)
|
(14)
|
Seloken/Toprol-XL
|
527
|
4
|
(6)
|
(4)
|
160
|
3
|
(14)
|
(12)
|
Atacand
|
227
|
2
|
(3)
|
(1)
|
80
|
2
|
10
|
11
|
Others
|
259
|
2
|
(16)
|
(14)
|
80
|
2
|
(6)
|
(5)
|
Total CVMD
|
5,327
|
36
|
(16)
|
(14)
|
1,773
|
36
|
(4)
|
(4)
|
Respiratory
|
Symbicort
|
2,051
|
14
|
(9)
|
(8)
|
668
|
14
|
(4)
|
(4)
|
Pulmicort
|
805
|
5
|
4
|
7
|
242
|
5
|
8
|
9
|
Daliresp/Daxas
|
145
|
1
|
28
|
28
|
53
|
1
|
26
|
26
|
Tudorza/Eklira
|
108
|
1
|
(19)
|
(18)
|
37
|
1
|
(21)
|
(21)
|
Duaklir
|
56
|
-
|
27
|
30
|
21
|
-
|
50
|
43
|
Bevespi
|
8
|
-
|
n/m
|
n/m
|
4
|
-
|
n/m
|
n/m
|
Others
|
199
|
1
|
(13)
|
(12)
|
67
|
1
|
(22)
|
(22)
|
Total Respiratory
|
3,372
|
23
|
(5)
|
(3)
|
1,092
|
22
|
(2)
|
(2)
|
Other
|
Nexium
|
1,525
|
10
|
(1)
|
-
|
469
|
10
|
(9)
|
(7)
|
Synagis
|
453
|
3
|
21
|
21
|
153
|
3
|
47
|
47
|
Losec/Prilosec
|
202
|
1
|
(7)
|
(5)
|
66
|
1
|
(8)
|
(8)
|
Seroquel XR
|
224
|
2
|
(64)
|
(64)
|
62
|
1
|
(67)
|
(68)
|
Movantik/Moventig
|
92
|
1
|
42
|
42
|
30
|
1
|
20
|
20
|
FluMist/Fluenz
|
20
|
-
|
(46)
|
(46)
|
20
|
-
|
(23)
|
(23)
|
Others
|
546
|
4
|
(40)
|
(39)
|
191
|
4
|
(30)
|
(29)
|
Total Other
|
3,062
|
21
|
(19)
|
(18)
|
991
|
20
|
(18)
|
(17)
|
|
Total
Product Sales
|
14,665
|
100
|
(9)
|
(8)
|
4,882
|
100
|
(3)
|
(2)
|
*Due to rounding, the sum of individual brand percentages may not
agree to totals.
Product Sales Summary
_______________________________________________________________________________________
ONCOLOGY
Product
Sales of $2,904m; an increase of 18%
(19% at CER). Oncology Product Sales represented 20% of
total Product Sales, up from 15% in the first nine months of
2016.
Lung Cancer
Tagrisso
Product
Sales of $651m; an increase of
136% (138% at CER).
Within Emerging Markets, Tagrisso was approved in China in March 2017 as the first
AstraZeneca medicine under the China FDA's Priority Review pathway.
Sales in the US and Europe were $277m and $124m, respectively.
Sales grew by 54% year-on-year in the US, with progress in
T790M-mutation testing rates accompanied by the launch of a new
diagnostic-testing voucher programme for patients. In Europe,
where Tagrisso was launched in 2016, sales of $124m were driven
by a continued uptake and positive reimbursement decisions, most
recently in Italy, Portugal and Sweden.
Testing rates in Japan, where Tagrisso was also launched in 2016, exceeded 90%, with
year-to-date sales of $158m (FY 2016: $82m) reflecting a high
penetration rate in the currently-approved 2nd-line T790M-mutation
setting. Sequential quarterly sales declined in the quarter in
Japan, reflecting the one-time impact of the ending of the Ryotanki
restriction in Q2 2017. This regulation in Japan restricts
prescriptions for medicines in their first year on the market to
just two weeks of supply.
To date, Tagrisso has received regulatory approval in over 50
countries.
Iressa
Product
Sales of $398m; an increase of
1% (2% at CER).
Emerging Markets
sales increased by 7% (8% at CER) to $200m. China Product Sales
increased by 17% (22% at CER) to $115m, reflecting an improvement
in patient access following the National Negotiation process in
2016. Iressa was subsequently included on the National
Reimbursement Drug List (NRDL). Other Emerging Markets sales were
negatively impacted by competition from branded and generic
medicines, including in South Korea.
Sales
in the US increased by 69% to $27m and declined in Europe by 12% to
$80m. Given the significant future potential of Tagrisso, the Company continues to
prioritise the ongoing launch of Tagrisso in established markets over
commercial support for Iressa.
Other Cancers
Lynparza
Product
Sales of $197m; an increase of 26%.
Lynparza was available to patients in
over 30 countries by the end of the period, with regulatory reviews
underway in additional countries. On 17 August 2017, Lynparza received an additional, broad
approval in the US, namely for patients regardless of BRCA-mutation
status, for the treatment of 2nd-line ovarian cancer with a new
tablet formulation. This was in addition to the full approval for
the later-line treatment of patients with BRCA-mutant ovarian
cancer. This was followed by an immediate encouraging uplift in
new-patient starts.
US
sales declined by 9% in the year to
date to $87m, reflecting the introduction of competing poly ADP
ribose polymerase (PARP)-inhibitor medicines in earlier lines of
treatment that were approved in broader patient populations.
Encouraging progress was made in the quarter, however, with sales
growth of 9% reflecting the aforementioned approval for the
treatment of 2nd-line ovarian cancer.
Sales in Europe increased by 68% (70% at CER) to $94m, following a
number of successful launches.
On 27
July 2017, AstraZeneca and MSD announced a global strategic
oncology collaboration to co-develop Lynparza and potential medicine
selumetinib for multiple cancer types. The companies intend to
develop Lynparza and
selumetinib jointly, both in monotherapy and in combination with
other potential medicines. Independently, the companies will
develop Lynparza and
selumetinib in combination with their respective PD-L1 and PD-1
medicines, Imfinzi and
pembrolizumab, separately. MSD is planning to co-commercialise
Lynparza and potential
medicine selumetinib with the Company in due course.
Imfinzi
Product
Sales of $1m; launched in the US on 1 May 2017.
Approved
under the US FDA's Accelerated-Approval pathway and launched on the
same day as a fast-to-market, limited commercial opportunity,
Imfinzi is currently
indicated for the treatment of patients with locally advanced or
metastatic urothelial carcinoma (bladder cancer) who have disease
progression during or following platinum-containing chemotherapy,
or whose disease has progressed within 12 months of receiving
platinum-containing chemotherapy before (neo-adjuvant) or after
(adjuvant) surgery. At present, there are five immunotherapy
medicines approved for the treatment of bladder cancer in the US.
The Company is actively preparing for the potential launch of
Imfinzi in
locally-advanced, unresectable non-small cell lung cancer (NSCLC)
in H1 2018, given US FDA regulatory submission acceptance received
in October 2017.
Legacy: Faslodex
Product
Sales of $703m; an increase of
16%.
China
sales grew by 29% (36% at CER) to $18m in the year to date, which
followed the recent successful negotiation and subsequent inclusion
on the NRDL; overall Faslodex Emerging Markets sales grew by
26% (23% at CER) to $88m. In May 2017, the Company received a label
extension for Faslodex in
Russia in the 1st-line monotherapy setting, based on data from the
FALCON trial. Russia sales grew by 50% in the year to date (30% at
CER) to $15m.
US sales increased by 15% to $368m, mainly reflecting a continued
strong uptake of the combination with palbociclib, a medicine
approved for the treatment of hormone-receptor-positive (HR+)
breast cancer. Europe sales increased by 15% (16% at CER) to
$194m.
In June 2017, a label extension based upon the FALCON trial in the
1st-line setting was approved in Japan; sales grew by 11% (13% at
CER) in the year to date to $50m.
Legacy: Zoladex
Product
Sales of $548m; a decline of 6% (5% at
CER).
Emerging Markets
sales growth of 9% (10% at CER) to $260m particularly reflected an
increase in China sales of 21% (26% at CER) to $127m. Sales in
Europe declined by 11% (8% at CER) to $104m. Sales in Established
Rest Of World (ROW, comprising Japan, Canada, Australia and New
Zealand) declined by 16% (15% at CER) to $168m, driven by lower
levels of use. On 31 March 2017, the Company completed an agreement
with TerSera for the commercial rights to Zoladex in the US and
Canada.
CVMD
Product
Sales of $5,327m; a decline of
16% (14% at CER). CVMD Product Sales represented 36% of
total Product Sales, down from 39% in the first nine months of
2016.
Brilinta
Product
Sales of $780m; an increase of 29% (31% at CER).
Emerging Markets
sales of Brilinta in the
year to date grew by 29% (32% at CER) to $175m, with China Product
Sales increasing by 32% (38% at CER) to $86m. This was followed by
the recent successful negotiation and subsequent inclusion of
Brilinta on the NRDL.
Growth in Emerging Markets was reflected in a continued
outperformance of the growth of the oral anti-platelet market.
Strong sales growth was delivered in many markets, including other
parts of Asia Pacific, as well as in Russia.
US sales of Brilinta, at $355m, represented an increase of 46%
in the year to date, including growth of 67% in the quarter;
Brilinta achieved record
total-prescription market share of 6.8% at the end of the period.
Days-of-therapy volume market-share data was particularly
encouraging. The performance reflected the growth in demand, driven
by updated preferred guidelines from the American College of
Cardiology and the American Heart Association in 2016, as well as
the narrowing of a competitor's label; Brilinta remained the branded oral
anti-platelet market leader in the US. Sales of Brilique in Europe increased by 11%
(13% at CER) to $213m, reflecting indication leadership across a
number of markets.
Farxiga
Product
Sales of $742m; an increase of
24%.
Emerging Markets
sales increased by 74% (72% at CER) to $160m, reflecting ongoing
launches and improved levels of patient access. In March 2017,
Forxiga became the first
sodium-glucose co-transporter 2 (SGLT2) inhibitor medicine to be
approved in China.
US
sales increased by 4% to $339m, with sales subdued by the impact of
affordability programmes. Given recent changes to these programmes,
the Company saw a diminished impact on sales in the quarter;
importantly, Farxiga's
market share in the SGLT2 class remained stable in the period.
Overall, the SGLT2 class gained market share from other classes of
type-2 diabetes medicines, supported by growing evidence around the
cardiovascular (CV) benefits of the class.
Sales
in Europe increased by 26% (27% at CER) to $171m as the medicine
continued to lead the growing class. In Japan, where Ono
Pharmaceutical Co., Ltd is a partner and records in-market sales,
sales to the partner amounted to $31m.
Onglyza
Product
Sales of $431m; a decline of
25%.
The
performance reflected adverse pressures on the dipeptidyl
peptidase-4 (DPP-4) class and an acceleration of ongoing Diabetes
market dynamics. Sales in Emerging Markets declined by 15% (16% at
CER) to $93m as the Company focused on Farxiga. Onglyza, however, entered the NRDL in
China in the period with year-to-date growth of 41% (47% at CER) to
$24m.
US
sales declined by 29% to $217m. Continued competitive pressures and
a lower market share were only partially offset by the favourable
impact of lower utilisation of patient-access programmes. Sales in
Europe declined by 24% (23% at CER) to $78m. In Japan, in-market
sales are recorded by Kyowa Hakko Kirin Co., Ltd, to whom sales
totalled $10m.
Bydureon/Byetta
Product
Sales of $555m; a decline of 13% (12% at CER).
Combined sales of
Bydureon and Byetta in Emerging Markets were $5m and
$9m, respectively. In 2016, AstraZeneca entered a strategic
collaboration with 3SBio Inc. for the rights to commercialise
Bydureon and Byetta in China. Combined US sales for Bydureon and Byetta were $424m, despite intense levels of
competition. Bydureon US
sales declined by 2% to $343m, representing 81% of total US
Bydureon and Byetta sales. The fall in US
Byetta sales continued in
the year to date; the decline of 36% to $81m reflected the
Company's promotional focus on once-weekly Bydureon over twice-daily Byetta. Combined sales in Europe
declined by 19% (17% at CER) to $91m.
Legacy: Crestor
Product
Sales of $1,771m; a decline of 36%
(35% at CER).
Sales
in China grew by 15% (19% at CER) to $273m. In the US, sales
declined by 78% to $246m, reflecting the market entry in July 2016
of multiple Crestor generic
medicines. In the quarter, the US
performance was flattered by a managed-market adjustment. In
Europe, sales declined by 22% (21% at CER) to $514m, reflecting the
increasing presence of generic medicines. In Japan, where Shionogi
Co. Ltd is a partner, Crestor maintained its position as the
leading statin, with growth of 1% (2% at CER) to $394m despite the
entry in the quarter of the first Crestor competitor. Multiple
Crestor generics are
expected to launch in Japan in due course.
RESPIRATORY
Product
Sales of $3,372m; a decline of
5% (3% at CER). Respiratory Product Sales represented 23% of total
Product Sales, up from 22% in the first nine months of
2016.
Symbicort
Product
Sales of $2,051m; a decline of 9% (8%
at CER).
Symbicort continued to lead the global market by volume
within the inhaled corticosteroids (ICS) / Long-Acting Beta Agonist
(LABA) class. Emerging Markets sales grew by 7% (8% at CER) to
$322m, reflecting growth in China of 13% (18% at CER) to $136m and
in Latin America (ex-Brazil), where sales grew by 27% (31% at CER)
to $33m.
In contrast, US sales declined by 15% to $811m, in
line with expectations of continued challenging conditions; these
conditions were a result of the impact of managed-care access
programmes on pricing within the class. Competition also remained
intense from other classes, such as Long-Acting Muscarinic
Antagonist (LAMA) / LABA combination medicines. In Europe, sales
declined by 13% (11% at CER) to $590m, reflecting competition from
other branded and Symbicort-analogue medicines.
In
Japan, where Astellas Pharma Co. Ltd assists as a promotional
partner, sales increased by 3% (5% at CER) to $151m.
Pulmicort
Product
Sales of $805m; an increase of 4% (7%
at CER).
Emerging
Markets sales increased by 14% (19% at CER) to $571m, reflecting
strong underlying volume growth, with sales in China, Middle East
and North Africa particularly encouraging. Emerging Markets
represented 71% of global sales. China sales increased by 13% (18%
at CER) to $463m and represented 58% of global sales. Usage in
China continued to increase, with the increasing prevalence of
acute COPD and paediatric asthma accompanied by continued
investment by the Company in new hospital nebulisation centres.
Legacy sales in the US and Europe declined by 22% to $107m and by
10% to $66m, respectively.
Daliresp/Daxas
Product
Sales of $145m; an increase of
28%.
US
sales, representing 86% of global sales, increased by 23% to $124m,
driven by favourable pricing and greater use of the medicine which
is the only oral, selective, long-acting inhibitor of the enzyme
phosphodiesterase-4, an inflammatory agent in COPD. Sales outside
the US increased by 75% to $21m.
Tudorza/Eklira
Product
Sales of $108m; a decline of 19% (18%
at CER).
Sales in the US declined by 23% to $47m, reflecting lower use of
inhaled monotherapy medicines for COPD and the Company's commercial
focus on the launch of Bevespi
Aerosphere. On 17 March
2017, AstraZeneca announced that it had entered a strategic
collaboration with Circassia for the development and
commercialisation of Tudorza in the US. Circassia began its
promotion of Tudorza in the
US in May 2017; AstraZeneca will continue to book Product Sales in
the US. Sales in Europe declined by 15% (14% at CER) to
$55m.
Duaklir
Product Sales of $56m; an increase of 27% (30% at
CER).
Duaklir, the Company's first inhaled dual bronchodilator,
is now available for patients in over 25 countries. The growth
in sales in the year to date was favourably impacted by the
performances in Germany and the UK and the recent launch in Italy.
Duaklir is expected to be
submitted for US regulatory review in H1 2018. Duaklir is a registered trademark in
certain European countries. The US trademark is to be
confirmed.
Bevespi
Product Sales of $8m; launched in 2017.
Bevespi Aerosphere was launched commercially in the US
during the first quarter of 2017. Prescriptions in the period
tracked in line with other LAMA/LABA launches. The overall
LAMA/LABA class in the US, however, continued to grow more slowly
than anticipated. Bevespi
Aerosphere was the first
product launched using the Company's Aerosphere co-suspension Delivery
Technology delivered in a pressurised metered-dose inhaler
(pMDI).
OTHER
Product
Sales of $3,062m; a decline of 19%
(18% at CER). Other Product Sales represented 21% of total
Product Sales, down from 23% in the first nine months of
2016.
Nexium
Product
Sales of $1,525m; 1% decline (stable
at CER).
Emerging
Markets sales declined by 5% (2% at CER) to $516m; however, sales
increased by 6% to $442m in the US. The latter performance was
flattered by returns adjustments related to the loss of exclusivity
in 2015. Sales in Europe declined by 7% to $176m. In Japan, where
Daiichi Sankyo is a partner, sales increased by 6% (8% at CER) to
$330m.
Synagis
Product
Sales of $453m; an increase of
21%.
US
sales increased by 6% to $182m, despite restrictive guidelines from
the American Academy of Pediatrics Committee on Infectious
Diseases, which reduced the number of patients eligible for
preventative therapy with Synagis. Product Sales to AbbVie Inc.,
which is responsible for the commercialisation of Synagis in over 80 countries outside
the US, increased by 33% to $271m, flattered by an element of
true-up adjustments.
Seroquel XR
Product
Sales of $224m; a decline of
64%.
Sales of Seroquel XR
in the US declined by 77% to $103m.
Since November 2016, several competitors have launched
generic Seroquel XR
medicines in the US. Sales of
Seroquel XR
in Europe declined by 42% to $61m,
also reflecting the impact of generic-medicine
competition.
FluMist/Fluenz
Product
Sales of $20m; a decrease of
46%.
FluMist is approved by the FDA for the 2017-2018 influenza
season and will be available in the US. No US sales of FluMist were recorded in the quarter,
however, due to the adverse US Advisory Committee on Immunization
Practices (ACIP) recommendation for use during the 2017-2018
influenza season. FluMist
continues to be recommended for use outside the US.
Sales
in Europe declined by 14% to $18m primarily driven by lower usage
rates in Germany that reflected the competitive environment and
parity recommendations for injectable vaccines, which more than
offset the favourable impact of the UK National Immunisation
Programme. Fluenz is the
vaccine of choice in the UK for children aged 2-17
years.
Regional Product Sales
_______________________________________________________________________________________
|
YTD 2017
|
Q3 2017
|
$m
|
% of total1
|
% change
|
$m
|
% of total
|
% change
|
Actual
|
CER
|
Actual
|
CER
|
Emerging
Markets2
|
4,519
|
31
|
5
|
7
|
1,515
|
31
|
9
|
10
|
|
China
|
2,142
|
15
|
6
|
10
|
723
|
15
|
12
|
14
|
|
Ex. China
|
2,377
|
16
|
4
|
5
|
792
|
16
|
5
|
7
|
|
|
|
|
|
|
|
|
|
US
|
4,399
|
30
|
(23)
|
(23)
|
1,386
|
28
|
(10)
|
(10)
|
|
|
|
|
|
|
|
|
|
Europe
|
3,460
|
24
|
(7)
|
(6)
|
1,188
|
24
|
(6)
|
(8)
|
|
|
|
|
|
|
|
|
|
Established
ROW
|
2,287
|
16
|
1
|
1
|
793
|
16
|
(4)
|
-
|
|
Japan
|
1,645
|
11
|
3
|
5
|
578
|
12
|
(3)
|
4
|
|
Canada
|
353
|
2
|
(5)
|
(6)
|
115
|
2
|
(9)
|
(10)
|
|
Other
Established ROW
|
289
|
2
|
(6)
|
(9)
|
100
|
2
|
(6)
|
(10)
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Total
|
14,665
|
100
|
(9)
|
(8)
|
4,882
|
100
|
(3)
|
(2)
|
1 Due to
rounding, the sum of individual brand percentages may not agree to
totals.
2 Emerging
Markets comprises all remaining Rest of World markets, including
Brazil, China, India, Mexico, Russia and Turkey.
Emerging Markets
Product
Sales of $4,519m; an increase of 5% (7% at CER).
China
sales grew by 6% (10% at CER) to $2,142m, representing 47% of total
Emerging Markets sales. Onglyza and Iressa were included on the NRDL in
China in the period, as were Brilinta, Faslodex and Seroquel XR, following price
negotiation. Crestor also
had its 2nd-line usage restriction removed and Zoladex was reclassified from the
hormone and endocrine classification to oncology, which is expected
to continue to support growth.
Sales
in Latin America were impacted by ongoing economic conditions, with
sales in Latin America (ex-Brazil) declining by 8% (6% at CER) to
$335m. Brazil sales increased by 3% (but declined by 8% at CER) to
$274m. Russia sales increased by 10% (but declined by 7% at CER) to
$170m.
Despite
this, the Growth Platforms in Emerging Markets grew by 17% (20% at
CER) to $1,503m. Sales of Symbicort grew by 7% (8% at CER) to
$322m, reflecting higher prescription demand. Tagrisso launches in Emerging Markets
led to year-to-date sales of $85m. Tagrisso was launched in China in April
2017; China sales of Tagrisso totalled $53m in the year to
date. Brilinta also
received provincial reimbursement listing in China for the period
across more than 15 provinces.
US
Product
Sales of $4,399m; a decline of
23%.
The decline in sales reflected generic-medicine
launches that impacted sales of Crestor and Seroquel XR. Unfavourable managed-care pricing and continued
competitive intensity impacted sales of Symbicort, which declined by 15% to $811m. The New Oncology
Growth Platform in the US, however, grew by 34% to $392m, primarily
reflecting encouraging Tagrisso sales growth of 54% to $277m in the year to date
(YTD 2016: $180m). Brilinta grew by 46% in the US to $355m. The New CVMD
Growth Platform declined by 1% in the US to $1,370m, reflecting the
competitive environment in Diabetes.
Europe
Product
Sales of $3,460m; a decline of 7% (6%
at CER).
The New Oncology Growth Platform in Europe grew by
108% (110% at CER) to $218m, partly driven by Tagrisso sales of $124m. Lynparza sales of $94m represented growth of 68% (70% at
CER). Forxiga sales growth of 26% (27% at CER) to $171m was
accompanied by Brilique growth of 11% (13% at CER) to $213m. These
performances were more than offset by declines in other areas,
including a 13% decline (11% at CER) in Symbicort sales to $590m. Symbicort maintained its position, however, as the number
one ICS/LABA medicine, despite competition from branded and
analogue medicines. Crestor sales declined by 22% (21% at
CER) to $514m, reflecting the increasing presence of generic
medicines.
Established ROW
Product
Sales of $2,287m; an increase of
1%.
Japan sales increased by 3% (5% at CER) to
$1,645m, partly reflecting sales of Symbicort and the launch of Tagrisso. Symbicort sales in Japan increased by 3% (5% at CER) to
$151m and, following the launch in Japan in May 2016,
Tagrisso
sales in the year to date amounted to
$158m. The first Crestor competitor medicine was launched in Q3 2017, with
full generic competition anticipated from Q4 2017. Despite the
magnitude of the impact of brand equity in the Japanese market, the
Company anticipates an impact from generic competition on
Crestor
Japan sales. Nexium sales in Japan increased by 6% (8% at CER) to
$330m and sales of Forxiga increased by 55% (60% at CER) to
$31m.
Financial Performance
________________________________________________________________________________________
|
Reported
|
YTD 2017
|
YTD 2016
|
Actual
|
CER
|
$m
|
$m
|
% change
|
|
Total
Revenue
|
16,688
|
17,417
|
(4)
|
(3)
|
Product Sales
|
14,665
|
16,059
|
(9)
|
(8)
|
Externalisation Revenue
|
2,023
|
1,358
|
49
|
50
|
|
|
|
|
|
Cost of
Sales
|
(3,093)
|
(2,966)
|
4
|
9
|
\
|
|
|
|
|
Gross
Profit
|
13,595
|
14,451
|
(6)
|
(5)
|
Gross Margin*
|
80.3%
|
81.7%
|
-1
|
-2
|
|
|
|
|
|
Distribution
Expense
|
(225)
|
(243)
|
(8)
|
(4)
|
% Total Revenue
|
1.3%
|
1.4%
|
-
|
-
|
R&D
Expense
|
(4,206)
|
(4,347)
|
(3)
|
(1)
|
% Total Revenue
|
25.2%
|
25.0%
|
-
|
-1
|
SG&A
Expense
|
(7,155)
|
(8,027)
|
(11)
|
(9)
|
% Total Revenue
|
42.9%
|
46.1%
|
+3
|
+3
|
Other
Operating Income and Expense
|
982
|
535
|
83
|
86
|
% Total Revenue
|
5.9%
|
3.1%
|
+3
|
+3
|
|
|
|
|
|
Operating
Profit
|
2,991
|
2,369
|
26
|
16
|
% Total Revenue
|
17.9%
|
13.6%
|
+4
|
+3
|
Net
Finance Expense
|
(1,128)
|
(978)
|
15
|
4
|
Joint
Ventures and Associates
|
(43)
|
(22)
|
89
|
89
|
Profit
Before Tax
|
1,820
|
1,369
|
33
|
24
|
Taxation
|
(213)
|
220
|
|
|
Tax
Rate
|
12%
|
(16)%
|
|
|
Profit
After Tax
|
1,607
|
1,589
|
1
|
(6)
|
|
|
|
|
|
Earnings Per
Share
|
$1.34
|
$1.31
|
3
|
(4)
|
* Gross Margin, as a percentage of Product Sales, reflects Gross
Profit derived from Product Sales, divided by Product Sales. YTD
2017 Cost of Sales included $200m of costs relating to
externalisation activities, which is excluded from the calculation
of Gross Margin (YTD 2016: $32m).
|
Reported
|
Q3 2017
|
Q3 2016
|
Actual
|
CER
|
$m
|
$m
|
% change
|
Total
Revenue
|
6,232
|
5,699
|
9
|
10
|
Product Sales
|
4,882
|
5,025
|
(3)
|
(2)
|
Externalisation Revenue
|
1,350
|
674
|
n/m
|
n/m
|
|
|
|
|
|
Cost of
Sales
|
(1,249)
|
(900)
|
39
|
40
|
\
|
|
|
|
|
Gross
Profit
|
4,983
|
4,799
|
4
|
4
|
Gross Margin*
|
77.7%
|
82.2%
|
-4
|
-4
|
|
|
|
|
|
Distribution
Expense
|
(76)
|
(76)
|
(1)
|
1
|
% Total Revenue
|
1.2%
|
1.3%
|
-
|
-
|
R&D
Expense
|
(1,404)
|
(1,402)
|
-
|
1
|
% Total Revenue
|
22.5%
|
24.6%
|
+2
|
+2
|
SG&A
Expense
|
(2,497)
|
(2,403)
|
4
|
5
|
% Total Revenue
|
40.1%
|
42.2%
|
+2
|
+2
|
Other
Operating Income and Expense
|
143
|
110
|
29
|
29
|
% Total Revenue
|
2.3%
|
1.9%
|
-
|
-
|
|
|
|
|
|
Operating
Profit
|
1,149
|
1,028
|
12
|
9
|
% Total Revenue
|
18.4%
|
18.0%
|
-
|
-
|
Net
Finance Expense
|
(386)
|
(342)
|
13
|
5
|
Joint
Ventures and Associates
|
(17)
|
(10)
|
60
|
60
|
Profit
Before Tax
|
746
|
676
|
10
|
11
|
Taxation
|
(97)
|
319
|
|
|
Tax
Rate
|
13%
|
(47)%
|
|
|
Profit
After Tax
|
649
|
995
|
(35)
|
(36)
|
|
|
|
|
|
Earnings Per
Share
|
$0.54
|
$0.80
|
(32)
|
(33)
|
* Gross Margin, as a percentage of Product Sales, reflects Gross
Profit derived from Product Sales, divided by Product Sales. Q3
2017 Cost of Sales included $159m of costs relating to
externalisation activities (Q3 2016: $4m), which is excluded from
the calculation of Gross Margin.
Reconciliation
of Reported Profit Before Tax to EBITDA
|
YTD
2017
|
Q3
2017
|
|
$m
|
%
change
|
$m
|
%
change
|
|
|
Actual
|
CER
|
|
Actual
|
CER
|
Reported Profit
Before Tax
|
1,820
|
33
|
24
|
746
|
10
|
11
|
Net Finance
Expense
|
1,128
|
15
|
4
|
386
|
13
|
5
|
Joint Ventures and
Associates
|
43
|
89
|
89
|
17
|
60
|
60
|
Depreciation,
Amortisation and Impairment
|
1,929
|
9
|
12
|
655
|
7
|
7
|
EBITDA*
|
4,920
|
19
|
15
|
1,804
|
10
|
9
|
* The Company uses EBITDA as a non-GAAP measure in addition to its
Core Financial Measures.
Reconciliation
of Reported to Core Financial Measures
YTD
2017
|
Reported
|
Restructuring
|
Intangible Asset
Amortisation & Impairments
|
Diabetes Alliance
|
Other1
|
Core2
|
Core
|
Actual
|
CER
|
$m
|
$m
|
$m
|
$m
|
$m
|
$m
|
% change
|
Gross
Profit
|
13,595
|
128
|
103
|
-
|
-
|
13,826
|
(6)
|
(5)
|
Gross Margin3
|
80.3%
|
-
|
-
|
-
|
-
|
81.8%
|
-1
|
-1
|
|
|
|
|
|
|
|
|
|
Distribution
Expense
|
(225)
|
-
|
-
|
-
|
-
|
(225)
|
(8)
|
(4)
|
R&D
Expense
|
(4,206)
|
177
|
73
|
-
|
-
|
(3,956)
|
(5)
|
(2)
|
SG&A
Expense
|
(7,155)
|
265
|
773
|
235
|
204
|
(5,678)
|
(7)
|
(5)
|
Other
Operating Income and Expense
|
982
|
75
|
44
|
-
|
-
|
1,101
|
91
|
94
|
|
|
|
|
|
|
|
|
|
Operating
Profit
|
2,991
|
645
|
993
|
235
|
204
|
5,068
|
8
|
5
|
% Total Revenue
|
17.9%
|
-
|
-
|
-
|
-
|
30.4%
|
+3
|
+2
|
|
|
|
|
|
|
|
|
|
Net
Finance Expense
|
(1,128)
|
-
|
-
|
234
|
368
|
(526)
|
8
|
5
|
|
|
|
|
|
|
|
|
|
Taxation
|
(213)
|
(135)
|
(240)
|
(144)
|
(86)
|
(818)
|
n/m
|
n/m
|
|
|
|
|
|
|
|
|
|
Earnings Per
Share
|
$1.34
|
$0.40
|
$0.59
|
$0.26
|
$0.39
|
$2.98
|
(4)
|
(7)
|
1 Other
adjustments include discount unwind on acquisition-related
liabilities (see Note 4), provision charges related to certain
legal matters (see Note 5) and foreign-exchange gains and losses
relating to the classification of certain non-structural
intra-group loans.
2 Each of
the measures in the Core column in the above table are non-GAAP
measures.
3 Gross
Margin as a percentage of Product Sales reflects gross profit
derived from Product Sales, divided by Product Sales. YTD 2017 Cost
of Sales includes $200m of costs relating to externalisation
activities (YTD 2016: $32m), which is excluded from the calculation
of Gross Margin. Movements in Gross Margin are expressed in
percentage points.
Q3
2017
|
Reported
|
Restructuring
|
Intangible Asset
Amortisation & Impairments
|
Diabetes Alliance
|
Other1
|
Core2
|
Core
|
Actual
|
CER
|
$m
|
$m
|
$m
|
$m
|
$m
|
$m
|
% change
|
Gross
Profit
|
4,983
|
47
|
45
|
-
|
-
|
5,075
|
4
|
4
|
Gross Margin3
|
77.7%
|
-
|
-
|
-
|
-
|
79.6%
|
-4
|
-4
|
|
|
|
|
|
|
|
|
|
Distribution
Expense
|
(76)
|
-
|
-
|
-
|
-
|
(76)
|
(1)
|
1
|
R&D
Expense
|
(1,404)
|
35
|
30
|
-
|
-
|
(1,339)
|
-
|
-
|
SG&A
Expense
|
(2,497)
|
68
|
265
|
102
|
112
|
(1,950)
|
3
|
4
|
Other
Operating Income and Expense
|
143
|
(1)
|
1
|
-
|
-
|
143
|
32
|
32
|
|
|
|
|
|
|
|
|
|
Operating
Profit
|
1,149
|
149
|
341
|
102
|
112
|
1,853
|
9
|
9
|
% Total Revenue
|
18.4%
|
-
|
-
|
-
|
-
|
29.7%
|
-
|
-
|
|
|
|
|
|
|
|
|
|
Net
Finance Expense
|
(386)
|
-
|
-
|
70
|
147
|
(169)
|
(2)
|
3
|
|
|
|
|
|
|
|
|
|
Taxation
|
(97)
|
(31)
|
(78)
|
(37)
|
(46)
|
(289)
|
n/m
|
n/m
|
|
|
|
|
|
|
|
|
|
Earnings Per
Share
|
$0.54
|
$0.09
|
$0.21
|
$0.11
|
$0.17
|
$1.12
|
(15)
|
(17)
|
1 Other
adjustments include discount unwind on acquisition-related
liabilities (see Note 4), provision charges related to certain
legal matters (see Note 5) and foreign-exchange gains and losses
relating to the classification of certain non-structural
intra-group loans.
2 Each of
the measures in the Core column in the above table are non-GAAP
measures.
3 Gross
Margin as a percentage of Product Sales reflects gross profit
derived from Product Sales, divided by Product Sales. Q3 2017 Cost
of Sales included $159m of costs relating to externalisation
activities (Q3 2016: $4m), which is excluded from the calculation
of Gross Margin. Movements in Gross Margin are expressed in
percentage points.
Profit and Loss Commentary for the Year To Date
Gross Profit
Reported Gross
Profit declined by 6% (5% at CER) to $13,595m; Core Gross Profit
declined by 6% (5% at CER) to $13,826m. The $997m of
Externalisation Revenue received as part of the Lynparza and selumetinib collaboration
with MSD was outweighed by the receding effects of the Crestor and Seroquel XR loss of exclusivity in the
US.
The calculation of the Reported Gross and Core Gross
Margins excludes the impact of Externalisation
Revenue, thereby reflecting the underlying performance of
Product Sales. The Reported Gross Profit Margin declined by
one percentage point (two percentage points at CER) to 80.3%. The
Core Gross Profit margin declined by one percentage point to 81.8%.
The declines primarily reflected the effect of losses of
exclusivity, as well as the impact of supply agreements on
externalised or divested medicines.
In the
quarter, the Reported Gross Profit Margin declined by four
percentage points to 77.7%; the Core Gross Profit margin declined
by four percentage points to 79.6%. These declines partly reflected
the magnitude of the Gross Margins in the comparative period, as
well as manufacturing costs. The profit-share element of the
aforementioned MSD collaboration was and will continue to be
reflected in the Cost of Sales and the calculation of the Reported
and Core Gross Margin; this also adversely impacted the Gross
Margin performance in the quarter.
Operating Expenses: R&D
Reported R&D
costs declined by 3% (1% at CER) to $4,206m, with the Company
continuing to focus on resource prioritisation and cost discipline.
Core R&D costs declined by 5% (2% at CER) to $3,956m.
Core R&D costs over the full year
are expected to be broadly in line with those in FY 2016 at
CER.
Operating Expenses: SG&A
Reported SG&A
costs declined by 11% (9% at CER) to $7,155m, reflecting the
evolving shape of the business. Core SG&A costs declined by 7%
(5% at CER) to $5,678m.
In the
quarter, Reported SG&A costs increased by 4% (5% at CER) to
$2,497m, reflecting the magnitude of the reduction in Reported
SG&A costs in the comparative period, early investment in
forthcoming launches and commercial support in Emerging Markets,
particularly in China. Core SG&A costs in the quarter increased
by 3% (4% at CER) to $1,950m.
The
Company has continued to consolidate its operations used by
multiple parts of the business. It is committed to driving
simplification and standardisation through centralisation in shared
services of back-office and some middle-office activities that are
currently performed in various enabling units, including Finance,
HR, Procurement and IT. Instead of operating numerous
shared-service centres and managing outsourced vendors
independently, the recently-launched Global Business Services
organisation will, over time, provide integration of governance,
locations and business practices to all shared services and
outsourcing activities across AstraZeneca.
Other Operating Income and Expense
Where
AstraZeneca does not retain a significant ongoing interest in
medicines or potential new medicines, income from disposal
transactions is reported within Other Operating Income and Expense
in the Company's financial statements.
Reported
Other Operating Income and Expense increased by 83% (86% at CER) to
$982m and included:
●
$301m resulting from the sale of rights to
Seloken in Europe to
Recordati S.p.A (Recordati)
●
$165m resulting from the sale of the global
rights to Zomig outside
Japan to the Grünenthal Group (Grünenthal)
●
$161m of gains recognised on the sale of
short-term investments
●
$73m from the sale of Prilosec royalty streams
●
A milestone receipt of $50m in relation to the
disposal of Zavicefta to
Pfizer Inc.
●
Other gains on disposal of intangible
assets
Core
Other Operating Income and Expense increased by 91% (94% at CER) to
$1,101m, with the difference to Reported Other Operating Income and
Expense primarily driven by a restructuring charge taken against
land and buildings.
Operating Profit
Reported Operating
Profit increased by 26% (16% at CER) to $2,991m. The Reported
Operating Margin increased by four percentage points (three
percentage points at CER) at 18% of Total Revenue. Core Operating
Profit increased by 8% (5% at CER) to $5,068m. The Core Operating
Margin increased by three percentage points (two percentage points
at CER) to 30% of Total Revenue.
Net Finance Expense
Reported Net
Finance Expense increased by 15% to $1,128m, primarily reflecting
an adverse foreign-exchange impact relating to the classification
of certain non-structural intra-group loans. Reported Net Finance
Expense increased by 4% at CER, reflecting the impact of bond
issuances in May 2016 and June 2017. Excluding the discount unwind
on acquisition-related liabilities and the adverse foreign-exchange
impact, Core Net Finance Expense increased by 8% (5% at CER) to
$526m.
Profit Before Tax
Reported Profit
Before Tax increased by 33% (24% at CER) to $1,820m, reflecting the
higher Operating Profit partly offset by increased interest
charges. EBITDA increased by 19% (15% at CER) to
$4,920m.
Taxation
The
Reported and Core Tax Rates for the year to date were 12% and 18%
respectively. The Reported Tax Rate was lower than the 2017 UK
Corporation Tax Rate of 19.25% mainly due to the impact of tax
settlements and non-taxable fair value adjustments relating to
contingent consideration on business combinations. The Core Tax
Rate was lower than the 2017 UK Corporation Tax Rate of 19.25%
mainly due to the impact of tax settlements. The net cash tax paid
for the year to date was $473m, representing 26% of Reported Profit
Before Tax and 11% of Core Profit Before Tax.
The
Reported and Core Tax Rates for the comparative period were (16%)
and 8% respectively. These rates included a one-off benefit of
$453m following agreements between the Canadian tax authority and
the UK and Swedish tax authorities in respect of transfer pricing
arrangements for the 13-year period from 2004-2016. Excluding this
effect, the Reported and Core Tax Rates for the comparative period
were 17% and 19% respectively.
Earnings Per Share (EPS)
Reported EPS of
$1.34 represented an increase of 3% (a decline of 4% at CER). Core
EPS declined by 4% (7% at CER) to $2.98. The performance was driven
by a decline in Total Revenue, partly offset by continued progress
on cost control and an increase in Other Operating Income and
Expense. The difference in growth rates between Operating Profit
and EPS included the impact of a one-off tax benefit in Q3
2016.
Cash Flow and Balance Sheet
Cash Flow
The
Company generated a net cash inflow from operating activities of
$2,581m in the year to date, compared with $2,185m in the
comparative period. In Q3 2017, the Company received an upfront
cash receipt of $1.6bn from the global strategic oncology
collaboration with MSD, $997m of which was recorded in Operating
Profit, with the remainder deferred to the balance
sheet.
|
YTD 2017
|
YTD 2016
|
Difference
|
$m
|
$m
|
$m
|
Reported operating
profit
|
2,991
|
2,369
|
622
|
Depreciation,
amortisation and impairment
|
1,929
|
1,767
|
162
|
|
|
|
|
(Increase)/decrease
in working capital and short-term provisions
|
(228)
|
(472)
|
244
|
(Gains)/losses on
disposal of intangible assets
|
(735)
|
(198)
|
(537)
|
Fair
value movement on contingent consideration arising from business
combinations
|
(62)
|
132
|
(194)
|
Non-cash and other
movements
|
(322)
|
(479)
|
157
|
Interest
paid
|
(519)
|
(489)
|
(30)
|
Tax
paid
|
(473)
|
(445)
|
(28)
|
|
|
|
|
Net
cash inflow from operating activities
|
2,581
|
2,185
|
396
|
Net
cash outflows from investing activities were $686m in the year to
date compared with $4,572m in the comparative period. The
prior-period outflow included an upfront payment as part of the
majority investment in Acerta Pharma.
The
cash payment of contingent consideration in respect of the
Bristol-Myers Squibb Company share of the global Diabetes alliance
amounted to $235m in the year to date, which included a $100m
milestone payment in respect of Qtern and royalty
payments.
Net
cash outflows from financing activities were $2,924m in the year to
date compared to outflows of $1,020m in the comparative period,
which included cash inflows on the issuance of new long-term loans
of $2,483m.
Capital Expenditure
Capital
expenditure amounted to $849m in the year to date, which included
investment in the new global headquarters in Cambridge, UK, as well
as strategic manufacturing capacity in the UK, the US, Sweden and
China.
Debt and Capital Structure
At 30
September 2017, outstanding gross debt (interest-bearing loans and
borrowings) was $17,852m. Of the gross debt outstanding at 30
September 2017, $941m was due within one year. The Company's Net
Debt position at 30 September 2017 was $12,134m.
Reconciliation of Interest-Bearing Loans and Borrowings to Net
Debt
|
At 30 Sep 2017
|
At 31 Dec 2016
|
At 30 Sep 2016
|
$m
|
$m
|
$m
|
Cash
and cash equivalents
|
4,036
|
5,018
|
3,090
|
Other
investments
|
1,255
|
898
|
927
|
Net
derivatives
|
427
|
235
|
267
|
|
|
|
|
Cash,
short-term investments and derivatives
|
5,718
|
6,151
|
4,284
|
|
|
|
|
Overdrafts and
short-term borrowings
|
(930)
|
(451)
|
(1,075)
|
Finance
leases
|
(12)
|
(93)
|
(97)
|
Current
instalments of loans
|
-
|
(1,769)
|
(1,775)
|
Loans
due after one year
|
(16,910)
|
(14,495)
|
(14,736)
|
|
|
|
|
Interest-bearing
loans and borrowings (gross debt)
|
(17,852)
|
(16,808)
|
(17,683)
|
|
|
|
|
Net
Debt
|
(12,134)
|
(10,657)
|
(13,399)
|
Capital Allocation
The
Board's aim is to continue to strike a balance between the
interests of the business, financial creditors and the Company's
shareholders. After providing for investment in the business,
supporting the progressive dividend policy and maintaining a
strong, investment-grade credit rating, the Board will keep under
review potential investment in immediately earnings-accretive,
value-enhancing opportunities.
Foreign-Exchange Rates
Sensitivity
The
Company provides the following currency sensitivity
information:
|
Average Exchange Rates Versus USD
|
|
Impact Of 5% Strengthening in Exchange Rate Versus USD
($m)1
|
Currency
|
Primary Relevance
|
FY 2016
|
YTD 20172
|
% change
|
Total Revenue
|
Core Operating Profit
|
EUR
|
Product Sales
|
0.90
|
0.90
|
+1
|
+179
|
+123
|
JPY
|
Product Sales
|
108.84
|
111.93
|
-3
|
+104
|
+71
|
CNY
|
Product Sales
|
6.65
|
6.80
|
-2
|
+131
|
+74
|
SEK
|
Costs
|
8.56
|
8.62
|
-1
|
+7
|
-98
|
GBP
|
Costs
|
0.74
|
0.78
|
-6
|
+29
|
-131
|
Other3
|
|
|
|
|
+194
|
+124
|
1Based
on 2016 results at 2016 actual exchange rates.
2Based
on average daily spot rates between 1 January and 30 September
2017.
3Other
important currencies include AUD, BRL, CAD, KRW and
RUB.
Foreign-Exchange Hedging
AstraZeneca
monitors the impact of adverse currency movements on a portfolio
basis, recognising correlation effects. The Company may hedge to
protect against adverse impacts on cash flow over the short to
medium term. As at 30 September 2017, AstraZeneca had hedged 95% of
forecast short-term currency exposure that arises between the
booking and settlement dates on Product Sales and non-local
currency purchases.
Corporate and Business Development Update
________________________________________________________________________________________
The
highlights of the Company's corporate and business development
activities since the prior results announcement are shown
below:
a) AstraZeneca and MSD Establish Strategic Oncology
Collaboration
On 27
July 2017, AstraZeneca and MSD announced that they had entered a
global strategic oncology collaboration to co-develop and
co-commercialise Lynparza
for multiple cancer types. The companies will develop and
commercialise Lynparza
jointly, both as monotherapy and in combination with other
potential medicines. Independently, the companies will develop and
commercialise Lynparza in
combination with their respective PD-L1 and PD-1 medicines,
Imfinzi and
pembrolizumab.
The
companies will also jointly develop and commercialise AstraZeneca's
selumetinib, an oral, potent, selective inhibitor of MEK, part of
the mitogen-activated protein kinase pathway, currently being
developed for multiple indications including thyroid
cancer.
As part
of the agreement, MSD will pay AstraZeneca up to $8.5bn in total
consideration, including $1.6bn upfront, $750m for certain licence
options and up to $6.15bn contingent upon successful achievement of
future regulatory and sales milestones. The collaboration agreement
was completed upon signing. Under the terms of the agreement,
AstraZeneca subsequently recorded $997m under Externalisation
Revenue. AstraZeneca books all Product Sales of Lynparza and selumetinib; gross profits
due to MSD under the collaboration are recorded under Cost of
Sales. The initial, regulatory and commercial milestone payments
have been and will be recorded as Externalisation Revenue in the
Company's financial statements.
b) AstraZeneca and Aspen Enter Agreement for Remaining Rights to
Anaesthetics Medicines
On 14
September 2017, AstraZeneca announced that it had entered into an
agreement with Aspen, under which Aspen will acquire the residual
rights to the established anaesthetic medicines comprising
Diprivan, EMLA, Xylocaine/Xylocard/Xyloproct, Marcaine, Naropin, Carbocaine and Citanest.
AstraZeneca
entered into an agreement with Aspen in June 2016, under which
Aspen gained the exclusive commercialisation rights to the
medicines in markets outside the US. Under the terms of the new
agreement, Aspen will pay an upfront consideration of $555m and up
to $211m in performance-related milestones based on sales and gross
margin during the period from 1
September 2017 to 30 November 2019. AstraZeneca will
continue to manufacture and supply the medicines to Aspen during a
transition period of up to five years.
Under
the terms of the original agreement, Aspen made an upfront payment
to AstraZeneca of $520m and agreed to make future Product
Sales-related payments of up to $250m, as well as paying
double-digit percentage royalties on Product Sales. AstraZeneca
agreed to continue to manufacture and supply the medicines to Aspen
on a cost-plus basis for an initial period of 10
years.
The new
agreement did not impact the first Product Sales-related payment of
$150m due to AstraZeneca, which was recorded as Externalisation
Revenue in the Company's financial statements in the quarter. Under
the new agreement, Aspen will no longer pay royalties to
AstraZeneca. The remaining $100m Product Sales-related payment from
the original agreement will be made to AstraZeneca in 2018, if the
contingent terms are met and will be recorded as Other Operating
Income and Expense to reflect the reduced ongoing interest in the
medicines as a result of the new agreement. Furthermore, as
AstraZeneca will transition the manufacture and supply of the
medicines to Aspen and therefore will have a reduced ongoing
interest, the $555m initial and up to $211m sales and gross
margin-related payments from the new agreement will also be
recorded as Other Operating Income and Expense in the Company's
financial statements. The Company announced completion of the
agreement on 1 November 2017.
c) Agreement for Rights to Zomig
in
Japan
On 30
September 2017, AstraZeneca entered into an agreement with Sawai
Pharmaceuticals Company Ltd (Sawai) for the rights to Zomig in Japan. Zomig is a legacy medicine indicated
for the acute treatment of migraines and cluster headaches, an area
of medicine outside AstraZeneca's strategic focus. The divestment
of the rights to Zomig in
Japan follows an agreement entered into in June 2017, under which
Grünenthal acquired the rights to the medicine in all other
markets. AstraZeneca received initial revenue from Sawai which was
recorded as Other Operating Income and Expense in the Company's
financial statements.
d) AstraZeneca and Takeda Establish Collaboration to Develop and
Commercialise MEDI1341
On 29
August 2017, AstraZeneca and Takeda announced that they had entered
an agreement to jointly develop and commercialise MEDI1341, an
antibody currently in development as a potential treatment for
Parkinson's disease.
Under
the terms of the agreement, AstraZeneca will lead Phase I
development, while Takeda will lead future clinical-development
activities. The companies will share equally future development and
commercialisation costs for MEDI1341, as well as any future
revenues. Takeda will pay AstraZeneca up to $400m, including
initial income of $50m in Q3 2017 and development and sales
milestones thereafter, all recorded as Externalisation Revenue in
the Company's financial statements. Additional terms of the
agreement were not disclosed.
e) MedImmune and NewLink Announce Collaboration on Immuno-Oncology
Combination Clinical Trial
During
the period, it was announced that MedImmune, the Company's global
biologics research and development arm and NewLink Genetics
Corporation (NewLink Genetics) had entered into a clinical
collaboration agreement to evaluate the combination of Imfinzi, AstraZeneca's PD-L1 monoclonal
antibody and indoximod, NewLink Genetics' small molecule IDO
pathway inhibitor, along with standard-of-care chemotherapy for
patients with metastatic pancreatic cancer. The primary objective
for this randomised, placebo-controlled, Phase II trial is to
evaluate the immuno-oncology-based combination compared to
gemcitabine alone.
f) AstraZeneca and Incyte Enter Clinical-Trial Collaboration in
Early Lung Cancer
On 31
October 2017, the Company announced the expansion of its clinical
collaboration with Incyte Corporation (Incyte). As part of the
agreement, the companies will evaluate the efficacy and safety of
epacadostat, Incyte's investigational selective IDO1 enzyme
inhibitor, in combination with Imfinzi, compared to Imfinzi alone. The exclusive
collaboration for the trial population allows for the two companies
to conduct a Phase III trial in patients with locally-advanced
(Stage III), unresectable NSCLC whose disease has not progressed
following platinum-based chemotherapy concurrent with radiation
therapy (CRT). This agreement builds on the positive clinical data
readout from the PACIFIC trial, published in September
2017.
g) Senior Executive Team Changes
On 10
October 2017, David Fredrickson was appointed Executive
Vice-President, Global Head Oncology Business Unit (OBU), with
responsibility for sales, marketing, medical affairs and
diagnostics for Oncology medicines globally, as well as Oncology
commercial operations in the US, UK, Spain, Italy, Germany and
France. Prior to this appointment, Mr. Fredrickson was President
and Country Representative, Japan, where he was responsible for,
inter alia, the launch of
Tagrisso. Before that, as
Vice President, US for Oncology, Infectious Diseases and
Neuroscience, he was responsible for the US launches of
Tagrisso, Lynparza and Iressa. Mr. Fredrickson also spent a
number of years at Roche Holding Ltd.
He
became a member of the Senior Executive Team, reporting to the
Chief Executive Officer on 10 October 2017. Mr Fredrickson took
over leadership of the OBU from Jamie Freedman, who was appointed
President, AstraZeneca Canada, effective on the same
day.
Research and Development Update
________________________________________________________________________________________
A
comprehensive table with AstraZeneca's pipeline of medicines in
human trials can be found later in this document. Since the results
announcement on 27 July 2017 (the period):
Regulatory
Approvals
|
9
|
-
Faslodex - breast cancer
(1st line) (US)
-
Lynparza - ovarian cancer
(2nd line, 4th line/tablets) (US)
-
Calquence (acalabrutinib) -
MCL (2nd line) (US)
-
Brilinta - prior MI
(CN)
-
Farxiga + Bydureon - type-2 diabetes (US,
EU)
-
Bydureon BCise - type-2 diabetes
(US)
-
Symbicort - COPD
exacerbations (US)
|
Regulatory
Submission
Acceptances
|
6
|
-
Lynparza - breast cancer
(US, JP) (Priority Reviews)
-
Imfinzi - locally-advanced,
unresectable NSCLC ((US/Priority Review), EU, JP)
-
Bydureon BCise - type-2 diabetes
(EU)
|
Major
Phase III
Data Readouts
|
5
|
- Tagrisso - lung cancer (1st line) (FLAURA) (met primary
endpoint)
- Imfinzi - lung cancer (MYSTIC) (did not meet PFS primary
endpoint)
-
moxetumomab pasudotox - leukaemia (met primary
endpoint)
- Duaklir - COPD (met primary endpoint)
-
tralokinumab - severe, uncontrolled
asthma (did not meet primary endpoints)
|
Other Major Developments
|
3
|
-
Tagrisso - lung cancer (1st
line)
(Breakthrough
Therapy Designation, US)
-
Imfinzi - locally-advanced,
unresectable lung cancer
(Breakthrough
Therapy Designation, US)
-
Calquence - MCL (2nd
line)
(Breakthrough
Therapy Designation, US)
|
New Molecular Entities(NMEs) in Phase III Trials or Under
Regulatory Review
|
11
|
Oncology
- Imfinzi + treme - multiple cancers
-
moxetumomab pasudotox - leukaemia
-
selumetinib - thyroid cancer
-
savolitinib - kidney cancer
CVMD
- ZS-9 (sodium zirconium
cyclosilicate) - hyperkalaemia*
-
roxadustat - anaemia*
Respiratory
-
benralizumab - severe, uncontrolled asthma*, COPD
-
tralokinumab - severe, uncontrolled asthma
-
PT010 - COPD
Other
-
anifrolumab - lupus
-
lanabecestat - Alzheimer's disease
|
Projects in Clinical Pipeline
|
129
|
|
*Under Regulatory Review. The table shown above as at 9 November
2017.
ONCOLOGY
AstraZeneca has a deep-rooted heritage in Oncology
and offers a growing line of new medicines that has the potential
to transform patients' lives and the Company's future. At least six
Oncology medicines are expected to be launched between 2014 and
2020, of which Lynparza, Tagrisso, Imfinzi and Calquence are already benefitting patients. An extensive
pipeline of small-molecule and biologic medicines is in development
and the Company is committed to advancing New Oncology, primarily
focused on lung, ovarian, breast and blood cancers, as one of
AstraZeneca's five Growth Platforms.
At the recent 2017 European Society of Medical Oncology (ESMO)
annual meeting, AstraZeneca presented data from more than 40
abstracts, including two pivotal clinical-trial readouts selected
for late-breaking presentation at the Presidential Symposium.
Highlights included new data on approved and potential new
medicines from the Company's pipeline across multiple scientific
platforms and tumour types.
a) Faslodex
(breast
cancer)
On 28
August 2017, the Company announced approval in the US for the
expansion of Faslodex use
into advanced breast-cancer patients not previously treated with
endocrine (hormonal) medicines. The US FDA approval was based on
data from the Phase III FALCON trial, where Faslodex 500mg demonstrated superiority
over anastrozole 1mg in the treatment of locally-advanced or
metastatic breast cancer in post-menopausal patients who had not
received prior hormonal-based medicine for hormone
receptor-positive breast cancer. The FALCON trial data showed that
Faslodex significantly
reduced the risk of disease worsening or death by 20%.
During
the period, the Company announced that the Committee for Medicinal
Products for Human Use (CHMP) of the European Medicines Agency
(EMA) had adopted a positive opinion recommending a new indication
for Faslodex that will
expand its use to include combination therapy with palbociclib. The
combination use was designed for the treatment of patients with
hormone receptor-positive (HR+), human epidermal growth factor
receptor 2 negative (HER2-) locally-advanced or metastatic breast
cancer or who have received prior endocrine therapy. The CHMP
opinion was based on data from the Phase III PALOMA-3 trial which
demonstrated that the combination of Faslodex 500mg and palbociclib 125mg
resulted in a 4.9 month progression-free survival (PFS) improvement
over Faslodex and
placebo.
The
Company also announced during the period that the US FDA had
approved a new indication for Faslodex, expanding the indication to
include use with abemaciclib for the treatment of HR+, HER2-
advanced or metastatic breast cancer in patients with disease
progression after endocrine therapy. The US FDA approval was based
on data from the Phase III MONARCH 2 trial, which met the primary
endpoint of PFS.
Finally, the Company announced during the period the approval of
the supplemental New Drug Application (NDA) of Faslodex in combination with palbociclib in Japan, based on
data from the PALOMA-3 trial; the approval was for the treatment of
pre-menopausal breast cancer patients taking a luteinising
hormone-releasing hormone medication.
b) Lynparza
(multiple
cancers)
On 17 August 2017, the Company announced approval in the US
for Lynparza tablets as a maintenance treatment for patients
with platinum-sensitive recurrent ovarian cancer, regardless of
BRCA-mutation status. Lynparza tablets were also indicated for patients with
BRCA-mutated ovarian cancer beyond the 3rd-line setting, with the
Accelerated Approval converted to full approval. Data from two
randomised trials supported the new approval and the conversion of
the prior approval to full approval, originally based on a
single-arm trial.
Data from the Phase III SOLO-2 trial confirmed the benefit
of Lynparza in germline BRCA-mutated (gBRCAm) patients,
demonstrating a 70% reduced risk of disease progression or death
(HR, hazard ratio, 0.30) and improved PFS to 19.1 vs 5.5 months for
placebo by investigator-assessed analysis. Data from the Phase II
Study-19 trial showed that Lynparza reduced the risk of disease progression or death
by 65% and improved PFS compared to placebo in patients of any BRCA
status (HR 0.35; median PFS of 8.4 months vs 4.8 months for
placebo). Additionally, patients in Study 19, treated with
Lynparza
as a maintenance therapy, had a median
overall survival (OS) of 29.8 months vs 27.8 months for placebo (HR
0.73).
During the period, the Company received regulatory submission
acceptance in the US for Lynparza tablet's supplementary NDA based on the OlympiAD
trial data in breast cancer. In the period, the Company also
announced the submission of an NDA to Japan's Pharmaceuticals and
Medical Devices Agency for the use of Lynparza tablets in unresectable or recurrent BRCA-mutated
breast cancer, with a decision expected in the second half of
2018. The OlympiAD trial focused on patients with germline
BRCA-mutated, HER2- metastatic breast cancer who had been treated
previously with chemotherapy either in the neo-adjuvant, adjuvant
or metastatic settings. This followed the Phase III OlympiAD data
presented at the 2017 American Society of Clinical
Oncology annual meeting. Lynparza is the first PARP inhibitor with a regulatory
submission outside ovarian cancer.
c) Tagrisso
(lung
cancer)
At the recent ESMO Congress's Presidential Symposium, the Company
presented positive results from the Phase III FLAURA trial for
patients with 1st-line epidermal growth factor receptor
(EGFR)-mutated NSCLC. Patients treated with Tagrisso had less than half the risk of progression or
death compared with patients on erlotinib or gefitinib (HR 0.46).
The median PFS was 18.9 months for patients on Tagrisso vs. 10.2 months for patients in the comparator
arm. FLAURA demonstrated clinically-meaningful preliminary OS data
favouring Tagrisso, namely a 37% reduction in the risk of death. OS
data were 25% mature at the time of the interim analysis and a
final OS analysis is planned for a later stage.
Improvements in PFS with Tagrisso were consistent across all pre-specified patient
subgroups, with at least a 40% reduction in the risk of progression
or death, including in patients with or without central nervous
system metastases at trial entry, Asian/non-Asian patients,
patients with or without prior smoking history and patients with
exon 19 deletion/L858R. Patients treated with Tagrisso had more than double the median duration of
response than those on the comparator arm (17.2 months vs. 8.5
months), while the objective response rates (ORR) were
similar.
The US National Comprehensive Cancer Network (NCCN) guidelines were
updated on 28 September 2017 to include Tagrisso as a category-2A treatment option in NSCLC
patients with an EGFR mutation discovered prior to 1st-line
treatment. The medicine is not currently approved for treatment in
the 1st-line setting.
During the period, the Company and its partner Hutchison China
MediTech Limited presented
preliminary safety and clinical activity of savolitinib when given
in combination with Tagrisso in a Phase Ib trial at the International
Association for the Study of Lung Cancer 18th World Conference on
Lung Cancer in Japan. The trial was conducted in patients with
EGFR-mutation-positive NSCLC with mesenchymal epithelial transition
(MET)-amplification, who had progressed following 1st-line
treatment with a tyrosine kinase inhibitor (TKI). Early data on
safety and anti-tumour activity for savolitinib plus
Tagrisso
demonstrated a response according to
RECIST 1.1 criteria in 28% of patients previously treated with
third-generation T790M-directed EGFR TKIs, including
Tagrisso. In patients who had progressed after prior
treatment with a first- or second-generation EGFR inhibitor, 53% of
T790M-negative patients had a partial response, while 57% of
T790M-positive patients had a partial response. In the 66 patients
treated with savolitinib plus Tagrisso, the most common all-causality adverse events of
any grade were consistent with the known safety profiles of both
therapies, including nausea (44%), vomiting (35%), fatigue (30%),
and decreased appetite (30%).
d) Imfinzi
(lung and
other cancers)
The Company continues to advance multiple monotherapy trials
of Imfinzi and combination trials of Imfinzi with tremelimumab and other potential new
medicines:
Lung Cancer
During
the period, the Company maintained strong momentum in its early
immunotherapy efforts in lung cancer. On 31 July 2017, Imfinzi was granted Breakthrough
Therapy Designation by the US FDA for patients with
locally-advanced, unresectable NSCLC. PACIFIC is a Phase III,
randomised, double-blinded, placebo-controlled multi-centre trial
of Imfinzi as sequential
treatment in patients with locally-advanced (Stage III)
unresectable NSCLC, who had not progressed following standard
platinum-based chemotherapy concurrent with radiation therapy.
PACIFIC trial results presented at the 2017 ESMO annual meeting
showed a statistically-significant and clinically-meaningful PFS
benefit with Imfinzi and
also demonstrated a favourable risk/benefit profile. The trial will
continue in order to evaluate OS, the other primary endpoint, which
is anticipated to be assessed in 2019.
During
the period, the US FDA accepted a supplemental Biologics License
Application for Imfinzi for
the treatment of patients with locally-advanced, unresectable NSCLC
whose disease has not progressed following platinum-based
chemoradiation therapy. The agency granted Imfinzi Priority Review status in this
potential indication. The Company also recently submitted the data
from the PACIFIC trial to the EMA for the same indication and
received acceptance of the submission. Additional regulatory
submissions for the PACIFIC trial were made and/or accepted in the
period in Australia, Brazil, Canada, Japan and
Switzerland.
On 28
September 2017, the US NCCN Clinical Practice Guidelines in
Oncology were updated to include Imfinzi for the treatment of patients
with locally-advanced, unresectable NSCLC with no disease
progression after two or more cycles of definitive chemoradiation,
based on the data from the aforementioned PACIFIC trial.
The medicine is not currently approved
for treatment in the locally-advanced, unresectable NSCLC
setting.
The Company now expects the first data from the Phase III ARCTIC
trial in 3rd-line, PDL1-low/negative NSCLC to be available in H1
2018. The timeline reflects the event-driven nature of the trial as
the Company awaits greater maturity of OS data.
Ongoing key lung-cancer trials include:
Name
|
Phase
|
Line of Treatment
|
Population
|
Design
|
Timelines
|
Status
|
Monotherapy
|
ADJUVANT*
|
III
|
N/A
|
Stage Ib-IIIa NSCLC
|
Imfinzi vs
placebo
|
FPCD1
Q1 2015
First data anticipated 2020
|
Recruitment ongoing
|
PACIFIC
|
III
|
N/A
|
Locally-advanced (Stage III), unresectable NSCLC
|
Imfinzi vs
placebo
|
FPCD Q2 2014
LPCD2
Q2 2016
Final OS data anticipated 2019
|
Recruitment completed
PFS primary endpoint met
|
PEARL
|
III
|
1st line
|
NSCLC (Asia)
|
Imfinzi vs SoC
chemotherapy
|
FPCD Q1 2017
First data anticipated 2020
|
Recruitment ongoing
|
Combination therapy
|
MYSTIC
|
III
|
1st line
|
NSCLC
|
Imfinzi, Imfinzi + treme vs SoC chemotherapy
|
FPCD Q3 2015
LPCD Q3 2016
Final OS data anticipated H1 2018
|
Recruitment completed
PFS primary endpoint not met
|
NEPTUNE
|
III
|
1st line
|
NSCLC
|
Imfinzi + treme vs SoC
chemotherapy
|
FPCD Q4 2015
LPCD Q2 2017
First data anticipated H2 2018
|
Recruitment completed
|
POSEIDON
|
III
|
1st line
|
NSCLC
|
Imfinzi + SoC,
Imfinzi
+ treme + SoC vs SoC
chemotherapy
|
FPCD Q2 2017
First data anticipated 2019
|
Recruitment ongoing
|
ARCTIC
|
III
|
3rd line
|
PDL1- low/neg. NSCLC
|
Imfinzi, tremelimumab,
Imfinzi
+ treme vs SoC
chemotherapy
|
FPCD Q2 2015
LPCD Q3 2016
First data anticipated H1 2018
|
Recruitment completed
|
CASPIAN
|
III
|
1st line
|
Small-cell lung cancer (SCLC)
|
Imfinzi + SoC,
Imfinzi
+ treme + SoC vs SoC
chemotherapy
|
FPCD Q1 2017
First data anticipated 2020
|
Recruitment ongoing
|
*Conducted
by the National Cancer Institute of Canada
1First
Patient Commenced Dosing
2Last
Patient Commenced Dosing
Other Cancers
In November 2017, Imfinzi received approval in Canada, under the
Health Canada's accelerated-approval framework (Notice of
Compliance with Conditions (NOC/c) policy), for the treatment of
patients with locally-advanced or mUC who have disease progression
during or following platinum-containing chemotherapy, or whose
disease has progressed within 12 months of receiving
platinum-containing chemotherapy before (neoadjuvant) or after
(adjuvant) surgery. Approval was granted in an 'all-comer'
population based on both tumour response rate and duration of
response. Data from Study 1108, which supported this approval, was
shared at the recent 2017 ASCO annual meeting and showed a 17.0%
objective response rate (ORR) by BICR in all-comers and a 26.3% ORR
in patients with PDL1-positive tumours.
During the period, the Company amended its late-stage clinical
development programme in 1st-line locally-advanced or metastatic
urothelial carcinoma (bladder cancer). A refinement of the Phase
III DANUBE trial meant that OS became the only primary endpoint,
with the first data now anticipated in 2019. Patient enrolment was
also increased from 1,005 to 1,200 patients, reflecting the
inclusion of an expansion cohort in China.
The STRONG trial, a Phase IIIb, modular, five-year safety,
open-label trial commenced dosing in the period and will evaluate
the safety of a fixed-dose regimen equivalent to the current
weight-based dose regimen of Imfinzi + tremelimumab combination therapy or
Imfinzi
monotherapy in patients with advanced
solid tumours (via tumour-specific modules). The first tumour
module dosed was metastatic urothelial
carcinoma.
During
the period, the Company launched a new Phase III trial to assess
the safety and efficacy of Imfinzi monotherapy or Imfinzi plus tremelimumab combination
therapy versus standard of care in patients with unresectable
hepatocellular carcinoma (HCC, liver cancer). The HIMALAYA trial
will include a fixed dose of Imfinzi (1,500mg, monthly) and
tremelimumab (300mg).
Ongoing key trials are listed below:
Name
|
Phase
|
Line of Treatment
|
Population
|
Design
|
Timelines
|
Status
|
DANUBE
|
III
|
1st line
|
Cisplatin chemotherapy- eligible/
ineligible bladder cancer
|
Imfinzi, Imfinzi + treme vs SoC chemotherapy
|
FPCD Q4 2015
LPCD Q1 2017
First data anticipated 2019
|
Recruitment completed
|
KESTREL
|
III
|
1st line
|
Head and neck squamous cell carcinoma (HNSCC, head and neck
cancer)
|
Imfinzi, Imfinzi + treme vs SoC
|
FPCD Q4 2015
LPCD Q1 2017
First data anticipated H1 2018
|
Recruitment completed
|
EAGLE
|
III
|
2nd line
|
HNSCC
|
Imfinzi, Imfinzi + treme vs SoC
|
FPCD Q4 2015
LPCD Q3 2017
First data anticipated H1 2018
|
Recruitment completed
|
HIMALAYA
|
III
|
1st line
|
HCC
|
Imfinzi, Imfinzi + treme vs sorafenib
|
First data anticipated 2019
|
Recruitment ongoing
|
On 7
September 2017, the Company announced that its partner, Celgene
Corporation (Celgene) was informed by the US FDA that the agency
had placed a partial clinical hold on five trials and a full
clinical hold on one trial in the Celgene FUSION programme.
The trials are
testing Imfinzi in
combination with immunomodulatory agents such as lenalidomide, with
or without chemotherapy, in blood cancers such as multiple myeloma, chronic
lymphocytic leukaemia and lymphoma.
e) Calquence
(acalabrutinib) (blood cancer)
On 31 October 2017, the Company announced that the US FDA had
granted Accelerated Approval to Calquence, a kinase inhibitor indicated for the treatment
of adult patients with MCL who have received at least one prior
therapy. Calquence was approved under the FDA's Accelerated Approval
Program, based on overall response rate, which allows for earlier
approval of medicines that treat serious conditions and fill an
unmet medical need based on a surrogate endpoint.
Continued approval for this indication
may be contingent upon verification and description of clinical
benefit in confirmatory trials.
The
Accelerated Approval was based on results from the ACE-LY-004
trial, where Calquence
demonstrated an 80% ORR, with a 40% complete response and 40%
partial-response rate. Full results from the ACE-LY-004 clinical
trial will be presented in December 2017 at the 59th American
Society of Hematology annual meeting in Atlanta, US. The approval
followed acceptance of the submission and the granting of Priority
Review and Breakthrough Therapy Designation earlier in the period,
based on the totality of clinical data from the Calquence development programme,
including data from the Phase II ACE-LY-004 clinical
trial.
f) Moxetumomab pasudotox (leukaemia)
During
the period, the Company maintained momentum in its efforts in blood
cancers, with high-level results from a pivotal Phase III
single-arm trial of moxetumomab pasudotox, an anti-CD22 recombinant
immunotoxin, as treatment for adult patients with
relapsed/refractory hairy cell leukaemia (HCL) who have had at
least two prior lines of therapy. The clinical trial met its
primary endpoint of durable complete response. HCL is an orphan
disease with no cure and no established standard of care for
patients in late-line therapy who relapse or refractory to prior
therapies. AstraZeneca plans to submit the complete results from
the Phase III trial for presentation at a forthcoming medical
meeting.
CVMD
CV,
renal and metabolic diseases are key areas of focus for AstraZeneca
as the Company sets the challenge to better understand how its
portfolio of medicines might be used to help address multiple risk
factors or co-morbidities across CVMD. Today, AstraZeneca is
delivering life-changing results in the main CV-disease areas and
their complications. AstraZeneca is investing in the science to
demonstrate CV and mortality benefits by slowing the underlying
progression of CV-related disease and protecting the organs of the
CV system. Ultimately, AstraZeneca is looking to do more than just
slow CV-related disease, but to modify or even halt the natural
course of the disease itself and regenerate organs.
The net
result is a strong, continued commitment to new CVMD treatment
options that have the potential to deliver improved outcomes to
hundreds of millions of patients across the globe.
a) Brilique
(CV
disease)
During
the period, the China FDA approved Brilique 60mg tablets for patients with
a history of MI, following an MI event. The approval was based on
data from the PEGASUS trial and expanded the use of Brilique in combination with aspirin,
to reduce the rate of CV death, MI and stroke in patients with a
history of MI and at least one additional high-risk factor for
developing an atherothrombotic event.
During
the 2017 European Society of Cardiology congress in Barcelona,
AstraZeneca presented results from a new sub-analysis of data from
the Phase III PEGASUS trial. The trial showed that treatment with
Brilique 60mg twice daily
reduced the risk in CV-caused death (versus placebo) by 29% in
patients taking low-dose aspirin but still at high risk of an
atherothrombotic event.
b) Farxiga
(diabetes)
24-week
data from the DEPICT-1 trial was published in The Lancet Diabetes and Endocrinology
and presented at the 2017 European Association for the Study of
Diabetes (EASD) 53rd annual meeting in September 2017. The trial
showed that Farxiga, when
given as an oral adjunct to injectable insulin in patients with
inadequately-controlled type-1 diabetes, demonstrated significant
and clinically-relevant reductions from baseline in HbA1c, weight
reductions and lowered total daily insulin dosing at 24 weeks
compared to placebo at both the 5mg and 10mg dose. Furthermore, as
assessed by continuous glucose monitoring, treatment with
Farxiga at both doses
reduced mean glucose and glucose fluctuations (assessed by mean
amplitude of glycaemic excursions) and increased the percentage of
glucose readings in the target range (70-180mg/dL). Specifically,
patients treated with Farxiga 5mg and 10mg spent more than
two hours and more than 2.5 hours longer in the target glucose
range each day, respectively.
The
overall adverse event profile was in line with the known clinical
profile of Farxiga, with no
imbalance in adverse events reported. The occurrence of
hypoglycaemia overall, as well as severe hypoglycaemia, was not
increased in the Farxiga
treatment groups compared with placebo. Similarly, in this trial,
Farxiga was not associated
with an increase in the occurrence of definite diabetic
ketoacidosis (DKA) compared with placebo. Four (1%) events occurred
in the Farxiga 5mg group,
five (2%) occurred in the Farxiga 10mg group and three (1%)
occurred in the placebo group, respectively. Insulin pump failure
and missed insulin doses were the most frequent risk factors for
definite DKA in the placebo and Farxiga groups.
The DEPICT clinical programme for Farxiga is
ongoing; final results are required to evaluate the next regulatory
steps. Farxiga is
not currently approved for the treatment of type-1
diabetes.
c) Bydureon
(type-2
diabetes)
AstraZeneca
presented the full results from the EXSCEL (EXenatide Study of
Cardiovascular Event Lowering) trial at the aforementioned EASD
meeting. The trial demonstrated CV safety with Bydureon (exenatide extended-release)
in patients with type-2 diabetes across a range of CV
outcomes.
Bydureon did not increase the incidence of major adverse CV
events (MACE), a composite endpoint of CV death, non-fatal heart
attack or non-fatal stroke, compared to placebo (HR 0.91; 95%
confidence interval (CI): 0.83-1.00; p<0.001 for
non-inferiority). There were also fewer CV events observed in the
Bydureon arm of the trial
(839 (11.4%) versus 905 (12.2%)), although the primary efficacy
objective of a superior reduction in MACE did not meet statistical
significance (p=0.061). Additionally, in a pre-specified secondary
analysis, patients treated with exenatide had a 14% lower incidence
of death from all causes (HR: 0.86; 95% CI:
0.77-0.97).
During
the period, the US FDA approved the inclusion of data from the
DURATION-8 clinical trial into the Farxiga and Bydureon labels. DURATION-8 evaluated
the simultaneous combination of a GLP-1 receptor agonist with an
SGLT2 inhibitor on a background of metformin therapy, in high
baseline HbA1c patients with inadequate glycemic control. The
results demonstrated that combining agents that work in different
ways can significantly reduce HbA1c, as well as weight and systolic
blood pressure.
In
August 2017, the EMA approved the incorporation of DURATION-8 data
into the Bydureon label.
The label included updates to both the indication statement and the
clinical-trial section. DURATION-8 data is now represented in both
the Bydureon and
Forxiga European summary of
product characteristics.
In
October 2017, the Company announced that the US FDA had approved
Bydureon BCise (exenatide extended-release)
injectable suspension, a new formulation of Bydureon in an improved once-weekly,
single-dose BCise device for adults
with type-2 diabetes whose blood sugar remains uncontrolled on one
or more oral medicines in addition to diet and exercise, to improve
glycaemic control. AstraZeneca anticipates that Bydureon BCise will be available for patients in
the US in the first quarter of 2018. A regulatory application for
the new BCise device was also
accepted by the EMA in the period.
Major ongoing outcomes trials for patients are highlighted in the
following table:
Medicine
|
Trial
|
Mechanism
|
Population
|
Primary Endpoint
|
Timeline
|
Farxiga
|
DECLARE
|
SGLT2 inhibitor
|
~17,0001
patients with type-2
diabetes
|
Time to first occurrence of CV death, non-fatal MI or non-fatal
stroke
|
H2 2018 (final analysis)
|
Farxiga
|
DAPA-HF
|
SGLT2 inhibitor
|
~4,500 patients with heart failure (HF)
|
Time to first occurrence of CV death or hospitalisation for HF or
an urgent HF visit
|
FPCD Q1 2017
|
Farxiga
|
DAPA-CKD
|
SGLT2 inhibitor
|
~4,000 patients with chronic kidney disease (CKD)
|
Time to first occurrence of ≥50% sustained decline in
eGFR2
or reaching ESRD3
or CV death or renal
death
|
FPCD Q1 2017
|
Brilinta
|
THEMIS
|
P2Y12 receptor antagonist
|
~19,000 patients with type-2 diabetes
and coronary artery disease
without a history of
MI or stroke
|
Composite of
CV death, non-fatal MI
and non-fatal stroke
|
2019
|
Epanova
|
STRENGTH
|
Omega-3 carboxylic acids
|
~13,000 patients with mixed dyslipidaemia
|
Time to first occurrence of CV death, non-fatal MI or non-fatal
stroke
|
2019
|
1Includes
~10,000 patients who have had no prior index event (primary
prevention) and ~7,000 patients who have suffered an index event
(secondary prevention)
2Estimated
Glomerular Filtration Rate
3End-Stage
Renal Disease
d) ZS-9 (sodium zirconium cyclosilicate)
(hyperkalaemia)
In
April 2017, the EMA informed AstraZeneca that the Marketing
Authorisation Application decision process for ZS-9 was put on hold
until the agency had performed an inspection of the dedicated
substance-manufacturing facility in Texas, US. This followed
receipt of a second Complete Response Letter from the US FDA, as
announced on 17 March 2017. During the period, the Company made
further progress in addressing the manufacturing deficiencies
identified by the FDA inspection and expects to be able to
accommodate a new manufacturing inspection in due
course.
e) Roxadustat (anaemia)
During
the period, the Company and its partner FibroGen Inc. (Fibrogen)
announced the regulatory submission of an NDA for roxadustat with
the China FDA, concluding the rolling submission initiated in Q4
2016. The NDA was based on two Fibrogen-led Phase III trials,
conducted in China, that met their primary efficacy endpoints in
January 2017 respectively. If approved, roxadustat will be a
first-in-class medicine, with China being the first approval
country, ahead of other major markets.
RESPIRATORY
AstraZeneca's
Respiratory portfolio is aimed at transforming the treatment of
asthma and COPD through combination inhaled therapies, biologics
for the unmet medical needs of specific patient populations and an
early pipeline focused on disease modification.
The
growing range of medicines includes up to four anticipated launches
between 2017 and 2020. The capability in inhalation technology
spans both pressurised, metered-dose inhalers and dry-powder
inhalers to serve patient needs, as well as the innovative
Aerosphere co-suspension
Delivery Technology, a focus of AstraZeneca's future-platform
development for respiratory-disease combination
therapies.
a) Symbicort
(COPD)
On 11
September 2017, the US FDA approved Symbicort for the reduction of
exacerbations in patients with COPD. The approval was based on data
that evaluated COPD exacerbations as the primary endpoint in two
Phase IIIb trials (RISE and Study 003), supported by data from two
legacy Phase IIIa trials (SUN and SHINE). The approval meant
Symbicort was indicated to
reduce exacerbations; the medicine is also used as a maintenance
treatment for airflow obstruction in patients with COPD. The RISE
data was published in Respiratory
Medicine.
Following
clinical data from the Phase III SYGMA trials, examining
Symbicort Turbuhaler prescribed as an
anti-inflammatory reliever as needed in patients with mild asthma,
the primary objectives in severe-asthma exacerbation rates and
asthma control were met. A full evaluation of the SYGMA primary and
secondary objectives is ongoing and the results will be presented
at a forthcoming medical meeting.
b) Duaklir
(COPD)
On 7
September 2017, AstraZeneca announced positive top-line results
from the Phase III AMPLIFY trial for Duaklir, which met its primary
endpoints and demonstrated a statistically-significant improvement
in lung function in patients with moderate to very-severe stable
COPD, compared to each individual component (either aclidinium
bromide or formoterol). A full evaluation of the AMPLIFY data is
ongoing and further results will be presented at a forthcoming
medical meeting.
c) Bevespi
(COPD)
On 25
September 2017, the Company announced positive top-line results of
the Phase III PINNACLE 4 trial. The trial demonstrated a
statistically-significant improvement in lung function as measured
by trough forced expiratory volume in one second (FEV1), compared to its
monotherapy components and placebo, all administered twice daily
via pMDI to patients with moderate to very severe COPD. AstraZeneca
will make regulatory submissions for Bevespi Aerosphere in Japan and China in 2018,
based on data from PINNACLE 4, as well as previously-reported
trials.
During
the period, the first patient was randomised into AERISTO, a
head-to-head trial that is assessing the efficacy and safety of
Bevespi Aerosphere relative
to the competing dual bronchodilator, a fixed-dose combination of
umeclidinium and vilanterol, for patients with moderate to very
severe COPD.
d) Benralizumab (severe, uncontrolled asthma)
On 11
September 2017, results from a sub-group analysis of the SIROCCO
and CALIMA Phase III trials were presented at the aforementioned
ERS Congress. The results confirmed benralizumab's efficacy and
identified key predictive factors of those patients suffering from
severe, uncontrolled asthma that would respond best to treatment
with benralizumab. The results were published simultaneously in
The Lancet Respiratory
Medicine.
Benralizumab
is under regulatory review in the US, EU, Japan and several other
countries, with a US PDUFA date during the final quarter of 2017.
Regulatory decisions are anticipated elsewhere during H1
2018.
e) Tralokinumab (severe, uncontrolled asthma)
On 1
November 2017, AstraZeneca announced the top-line results of the
Phase III STRATOS 2 and TROPOS trials for tralokinumab, an
anti-interleukin-13 human monoclonal antibody, in severe,
uncontrolled asthma.
STRATOS
1 and 2 were Phase III multi-centre, randomised, double-blinded,
parallel-group, placebo-controlled trials designed to evaluate the
efficacy and safety of a regular, subcutaneous administration of
tralokinumab for 52 weeks in adult and adolescent patients with
severe, inadequately-controlled asthma, despite treatment with
inhaled corticosteroids plus LABA.
In the
STRATOS 2 trial, tralokinumab did not achieve a
statistically-significant reduction in the annual asthma
exacerbation rate, the primary endpoint, in patients with severe,
uncontrolled asthma and elevated levels of a biomarker, Fractional
exhaled Nitric Oxide, compared to placebo. In TROPOS, tralokinumab
did not achieve a statistically-significant reduction in oral
corticosteroid (OCS) use, the primary endpoint, when added to the
standard of care, in patients dependent on OCS. Full data from
STRATOS 1, STRATOS 2 and TROPOS will be presented at a forthcoming
medical meeting.
f) Tezepelumab (asthma)
At the
aforementioned ERS Congress, AstraZeneca and Amgen Inc. presented
results from the PATHWAY Phase IIb trial of tezepelumab, a
first-in-class treatment that blocks thymic stromal lymphopoietin
(TSLP), an upstream driver of inflammation in asthma. The trial met
its primary efficacy endpoint and the data demonstrated significant
and clinically-meaningful annual asthma exacerbation-rate
reductions of 61%, 71% and 66% in the tezepelumab arms receiving
either 70mg or 210mg every four weeks or 280mg every two weeks,
respectively, independent of baseline blood eosinophil count or
other type-2 inflammatory biomarkers. Tezepelumab also demonstrated
improvements in lung function at all doses and in asthma control at
the two higher doses. The trial results were simultaneously
published in the New England
Journal of Medicine.
OTHER
a) Tezepelumab (atopic dermatitis)
During
the period, the ALLEVIAD Phase IIa trial data showed that
tezepelumab did not meet statistical significance on the primary
endpoint (EASI 50) of the 12-week exploratory trial that evaluated
tezepelumab in moderate to severe atopic dermatitis (AD) as add-on
treatment to regular medium-to-high strength topical
glucocorticosteroids. Numeric differences in favour of tezepelumab,
however, were observed across a number of disease activity
endpoints (EASI, IGA and SCORAD response) compared to
placebo.
b) Anifrolumab (lupus)
During the period, the Company completed the enrolment of the
second Phase III trial (TULIP 2) of anifrolumab in patients with
moderate-to-severe systemic lupus erythematosus (SLE, or lupus).
Data readouts from both the TULIP 1 and TULIP 2 trials are expected
in H2 2018, with anticipated regulatory submissions in
2019.
In addition, the Company also completed enrolment during the period
of the Phase II SLE trial of a sub-cutaneous route of
administration of anifrolumab.
c) Lanabecestat
(Alzheimer's disease)
During
the period, the Company and Lilly completed enrolment of the Phase
II/III AMARANTH trial investigating the safety and efficacy of
lanabecestat compared with placebo in the treatment of early
Alzheimer's disease. A data
readout from the lanabecestat clinical programme is anticipated in
2019.
Development Pipeline 30 September 2017
________________________________________________________________________________________
AstraZeneca-sponsored or -directed trials
Phase III / Pivotal Phase II / Registration
New Molecular Entities (NMEs) and significant additional
indications
Regulatory
submission dates shown for assets in Phase III and beyond. As
disclosure of compound information is balanced by the business need
to maintain confidentiality, information in relation to some
compounds listed here has not been disclosed at this
time.
|
|
|
|
Estimated
Regulatory Acceptance Date /Submission Status
|
Compound
|
Mechanism
|
Area
Under Investigation
|
Date
Commenced Phase
|
US
|
EU
|
Japan
|
China
|
Oncology
|
|
|
|
|
|
|
|
Calquence# (acalabrutinib)
|
BTK
inhibitor
|
B-cell
malignancy
|
Q1
2015
|
Approved
|
|
|
|
Calquence# (acalabrutinib)
|
BTK
inhibitor
|
1st-line
chronic lymphocytic leukaemia
|
Q3
2015
|
2020
(Orphan
Drug Designation)
|
2020
(Orphan
designation)
|
|
|
Calquence# (acalabrutinib)
|
BTK
inhibitor
|
relapsed/refractory
chronic lymphocytic leukaemia, high risk
|
Q4
2015
|
2020
(Orphan
Drug Designation)
|
2020
(Orphan
designation)
|
|
|
Calquence# (acalabrutinib)
|
BTK
inhibitor
|
1st-line mantle cell lymphoma
|
Q1
2017
|
2023
|
|
|
|
savolitinib#
SAVOIR
|
MET inhibitor
|
papillary renal cell carcinoma
|
Q3
2017
|
2020
|
2020
|
|
|
selumetinibASTRA
|
MEK
inhibitor
|
differentiated
thyroid cancer
|
Q3
2013
|
H2
2018
(Orphan
Drug Designation)
|
H2
2018
|
|
|
moxetumomab
pasudotox#
PLAIT
|
anti-CD22
recombinantimmunotoxin
|
hairy
cell leukaemia
|
Q2
2013
|
H1
2018
(Orphan
Drug Designation)
|
|
|
|
Imfinzi#
+
tremelimumabARCTIC
|
PD-L1
mAb + CTLA-4 mAb
|
3rd-line
NSCLC
|
Q2
2015
|
H1
2018
|
H1
2018
|
H1
2018
|
|
Imfinzi#
+ tremelimumab
MYSTIC
|
PD-L1
mAb + CTLA-4 mAb
|
1st-line
NSCLC
|
Q3
2015
|
H2
2018
|
H2
2018
|
H2
2018
|
|
Imfinzi#
+ tremelimumab
NEPTUNE
|
PD-L1
mAb + CTLA-4 mAb
|
1st-line
NSCLC
|
Q4
2015
|
2019
|
2019
|
2019
|
2020
|
Imfinzi#PACIFIC
|
PD-L1
mAb
|
locally-advanced
(Stage III), NSCLC
|
Q2
2014
|
Accepted
(Breakthrough
Therapy Designation & Priority Review)
|
Accepted
|
Accepted
|
|
Imfinzi#
+ tremelimumab + chemotherapy
POSEIDON
|
PD-L1
mAb + CTLA-4 mAb
|
1st-line
NSCLC
|
Q2
2017
|
2019
|
2019
|
2019
|
2020
|
Imfinzi#
+ tremelimumab + SoC
CASPIAN
|
PD-L1
mAb + CTLA-4 mAb + SoC
|
1st-line
small cell lung cancer
|
Q1
2017
|
2020
|
2020
|
2020
|
|
Imfinzi#
+ tremelimumabKESTREL
|
PD-L1
mAb + CTLA-4 mAb
|
1st-line
HNSCC
|
Q4
2015
|
H2
2018
|
H2
2018
|
H2
2018
|
|
Imfinzi# +
tremelimumabEAGLE
|
PD-L1
mAb + CTLA-4 mAb
|
2nd-line
HNSCC
|
Q4
2015
|
H2
2018
|
H2
2018
|
H2
2018
|
|
Imfinzi#
+ tremelimumab
DANUBE
|
PD-L1
mAb + CTLA-4 mAb
|
1st-line
bladder cancer
|
Q4
2015
|
2019
|
2019
|
2019
|
|
Lynparza#¶+ cediranib
CONCERTO
|
PARP
inhibitor + VEGF inhibitor
|
recurrent
platinum-resistant ovarian cancer
|
Q1
2017
|
2019
|
|
|
|
CVMD
|
|
|
|
|
|
Epanova
|
omega-3 carboxylic acids
|
severe hypertriglycerid-aemia
|
|
Approved
|
|
2020
|
|
ZS-9 (sodium zirconium cyclosilicate)
|
potassium binder
|
hyperkalaemia
|
|
-
|
Accepted1
|
2019
|
|
roxadustat#
OLYMPUS (US) ROCKIES
(US)
|
hypoxia-inducible factor prolyl hydroxylase inhibitor
|
anaemia in CKD / end-stage renal disease
|
Q3
2014
|
H2
2018
|
|
|
Accepted2
|
Respiratory
|
Bevespi Aerosphere (PT003)
|
LABA/LAMA
|
COPD
|
|
Launched
|
Accepted
|
H2
2018
|
H2
2018
|
benralizumab#
CALIMA SIROCCO ZONDA
BISE
BORA
GREGALE
|
IL-5R mAb
|
severe, uncontrolled asthma
|
|
Accepted
|
Accepted
|
Accepted
|
2021
|
benralizumab#
TERRANOVA GALATHEA
|
IL-5R mAb
|
COPD
|
Q3
2014
|
H2
2018
|
H2
2018
|
2019
|
|
PT010
|
LABA/LAMA/
ICS
|
COPD
|
Q3
2015
|
2019
|
2019
|
H2
2018
|
H2
2018
|
tralokinumab
STRATOS 1,2
TROPOS
MESOS
|
IL-13 mAb
|
severe, uncontrolled asthma
|
Q3
2014
|
-
|
-
|
-
|
|
Other
|
|
|
|
|
|
|
|
anifrolumab#
TULIP
|
IFN-alphaR mAb
|
systemic lupus erythematosus
|
Q3
2015
|
2019
(Fast
Track)
|
2019
|
2019
|
|
lanabecestat |