a0602m
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 September 2023
Commission
File Number: 001-11960
AstraZeneca PLC
1
Francis Crick Avenue
Cambridge
Biomedical Campus
Cambridge
CB2 0AA
United
Kingdom
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AstraZeneca PLC
INDEX
TO EXHIBITS
1.
Fasenra Phase III EGPA trial met primary
endpoint
11 September 2023
Fasenra met
the primary endpoint in the MANDARA Phase III trial in eosinophilic
granulomatosis with polyangiitis (EGPA)
First head-to-head trial of biologics in EGPA, comparing a single
monthly injection of Fasenra to three injections per month of
mepolizumab
Positive high-level results from the MANDARA Phase III trial showed
AstraZeneca's Fasenra (benralizumab) met the primary endpoint of
the trial and demonstrated non-inferior rates of remission compared
to mepolizumab in patients with eosinophilic granulomatosis with
polyangiitis (EGPA) who were receiving oral corticosteroids (OCS)
with or without stable immunosuppressive
therapy.
MANDARA is the first Phase III head-to-head trial of biologics in
EGPA and compared the efficacy and safety
of Fasenra versus mepolizumab, the only currently
approved treatment.1,2 In
the blinded trial, patients were randomised to receive either a
single 30mg subcutaneous injection of Fasenra or three separate 100mg subcutaneous
injections of mepolizumab once every four weeks.1,2
EGPA is a rare, immune-mediated vasculitis that is caused by
inflammation of small to medium-sized blood
vessels.3,4 Approximately
half of patients with EGPA have concomitant adult-onset severe
eosinophilic asthma (SEA).5 EGPA
can result in damage to multiple organs, including lungs, skin,
heart, gastrointestinal tract and nerves, which accumulates over
time and without treatment can be fatal.3,6
Dr Michael Wechsler, Principal Investigator said: "The positive
MANDARA trial results are exciting because patients with
eosinophilic granulomatosis with polyangiitis today have limited
treatment options but face crippling symptoms, which can even be
fatal if not treated. This trial demonstrates that a biologic
medicine given in a single monthly injection could help patients
achieve remission rates comparable to the current standard of care,
adding to the importance of benralizumab as a potential treatment
option for eosinophilic granulomatosis with
polyangiitis."
Sharon Barr, Executive Vice President, BioPharmaceuticals R&D,
AstraZeneca, said: "The positive results from MANDARA demonstrate
that Fasenra, which has a unique mechanism of action and
directly targets eosinophils, can help patients achieve remission
from the debilitating impacts of this inflammatory disease with a
more convenient single monthly subcutaneous
injection."
The safety and tolerability profile for Fasenra in the trial was consistent with the known
profile of the medicine.
Full results from MANDARA will be presented at an upcoming medical
meeting and data will be shared with health authorities around the
world.
Fasenra is
a monoclonal antibody that binds directly to IL-5 receptor alpha on
eosinophils and attracts natural killer cells to induce rapid and
near-complete depletion of blood and tissue eosinophils in most
patients via apoptosis (programmed cell death).7,8
Fasenra is currently
approved as an add-on maintenance treatment for SEA in the US, EU,
Japan and other countries, and is approved for self-administration
in the US, EU and other countries.9,10 The
FDA granted Orphan Drug Designation for Fasenra for EGPA in 2018 and AstraZeneca continues
to explore Fasenra's potential beyond severe asthma, as a
treatment across many diseases where eosinophils are expected to
play a role.11-14
Notes
EGPA
EGPA, formerly known as Churg-Strauss Syndrome, is a rare,
immune-mediated inflammatory disease that is caused by inflammation
of small to medium-sized blood vessels.3,4 It
is estimated that 118,000 people throughout the world live with
EGPA.15
EGPA can result in damage to multiple organs, including lungs,
skin, heart, gastrointestinal tract and nerves.3 The
most common symptoms and signs include extreme fatigue, weight
loss, muscle and joint pain, rashes, nerve pain, sinus and nasal
symptoms, and shortness of breath.3,6 Without
treatment, the disease may be fatal.3,6
Elevated levels of eosinophils play a central role in EGPA disease
pathophysiology.4 All
patients with EGPA have very high levels of eosinophils at some
point in their disease, both in peripheral blood and in affected
tissues or organs.3,6 Approximately
half of patients with EGPA have concomitant adult-onset SEA, and
often have sinus and nasal symptoms.3,5
There are limited treatment options for EGPA. Patients are often
treated with chronic high-dose OCS and can experience recurrent
relapses when attempting to taper off OCS.6,16 Mepolizumab
is currently the only approved treatment for
EGPA.2
MANDARA
MANDARA was a randomised, double blind, double-dummy,
active-controlled, parallel group, multicentre 52-week Phase III
trial which compared the efficacy and safety
of Fasenra to mepolizumab in adult patients with
relapsing or refractory EGPA.1 In
the blinded trial, 140 patients were randomised 1:1 (70 per
treatment group) to receive either a single 30mg subcutaneous
injection of Fasenra or three separate 100mg subcutaneous
injections of mepolizumab once every four weeks.1
The primary endpoint was the proportion of patients who were in
remission at both weeks 36 and 48.1 Remission
is defined as Birmingham Vasculitis Activity Score (BVAS)=0 and OCS
dose less than or equal to 4mg/day.1 Fasenra remission
was compared to the historical placebo rate from mepolizumab's
Phase III trial, MIRRA.17 The
primary statistical analysis was to demonstrate non-inferiority
of Fasenra versus mepolizumab based on the primary
endpoint.
All patients who complete the 52-week double-blind treatment period
may be eligible to continue into an open label extension (OLE)
period, intended to allow each patient at least one year of
treatment with open-label Fasenra.1
Mepolizumab is a humanized IL-5 antagonist monoclonal
antibody.2
Fasenra
Fasenra (benralizumab) is
currently approved as an add-on maintenance treatment for SEA in
the US, EU, Japan and other countries, and is approved for
self-administration in the US, EU and other
countries.9,10 Fasenra has
been studied in almost 4,000 patients in global clinical
trials.18-22
Fasenra is in development
for other eosinophilic diseases including chronic obstructive
pulmonary disease, chronic rhinosinusitis with nasal polyps and
hypereosinophilic syndrome.12-14
Fasenra was developed by
AstraZeneca and is in-licensed from BioWa, Inc., a wholly-owned
subsidiary of Kyowa Kirin Co., Ltd., Japan.
Respiratory & Immunology
Respiratory & Immunology, part of AstraZeneca
BioPharmaceuticals, is a key disease area and growth driver to the
Company.
AstraZeneca is an established leader in respiratory care with a
50-year heritage and a growing portfolio of medicines in
immune-mediated diseases. The Company is committed to
addressing the vast unmet needs of these chronic, often
debilitating, diseases with a pipeline and portfolio of inhaled
medicines, biologics and new modalities aimed at previously
unreachable biologic targets. Our ambition is to deliver
life-changing medicines that help eliminate COPD as a leading cause
of death, eliminate asthma attacks and achieve clinical remission
in immune-mediated diseases.
AstraZeneca
AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led
biopharmaceutical company that focuses on the discovery,
development, and commercialisation of prescription medicines in
Oncology, Rare Diseases, and BioPharmaceuticals, including
Cardiovascular, Renal & Metabolism, and Respiratory &
Immunology. Based in Cambridge, UK, AstraZeneca operates in over
100 countries and its innovative medicines are used by millions of
patients worldwide. Please visit astrazeneca.com and
follow the Company on social
media @AstraZeneca.
References
1.
Clinicaltrials.gov. Efficacy and Safety of Benralizumab in EGPA
Compared to Mepolizumab. (MANDARA). Available at:
https://classic.clinicaltrials.gov/ct2/show/NCT04157348. [Last
accessed: September 2023].
2.
Mepolizumab US prescribing information. Available from:
https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/125526Orig1s021,761122Orig1s011Corrected_lbl.pdf
[Last accessed: September 2023].
3.
American Partnership for Eosinophilic Disorders. Eosinophilic
Granulomatosis with Polyangiitis (EGPA). Available at:
https://apfed.org/about-ead/eosinophilic-granulomatosis-with-polyangiitis/.
[Last accessed: September 2023].
4. Furuta S, Iwamoto T, Nakajima H.
Update on eosinophilic granulomatosis with
polyangiitis. Allergol
Int.
2019;68:430-436.
5. Cottin V, et al. Respiratory
manifestations of eosinophilic granulomatosis with polyangiitis
(Churg-Strauss). Eur Respir
J.
2016;48:1429-1441.
6. Baldini C, et al. Clinical
Manifestations and Treatment of Churg-Strauss
Syndrome. Rheum Dis Clin N
Am.
2010;36:527-543.
7. Kobleck R, et al. MEDI-563, a
humanized anti-IL-5 receptor a mAb with enhanced antibody-dependent
cell-mediated cytotoxicity function. J Allergy Clin
Immunol.
2010;125:1344-1353.e2.
8. Pham TH, et al. Reductions in
eosinophil biomarkers by benralizumab in patients with
asthma. Respir Med. 2016;111:21-29.
9.
AstraZeneca news release. Available at:
https://www.astrazeneca.com/media-centre/press-releases/2019/fasenra-approved-in-the-us-for-self-administration-in-a-new-pre-filled-auto-injector-the-fasenra-pen-04102019.html.
[Last accessed: September 2023].
10.
AstraZeneca news release. Available at:
https://www.astrazeneca.com/media-centre/press-releases/2019/fasenra-receives-positive-eu-chmp-opinion-for-self-administration-and-the-new-fasenra-pen-a-pre-filled-single-use-auto-injector-01072019.html.
[Last accessed: September 2023].
11.
AstraZeneca news release. Available at:
https://www.astrazeneca.com/media-centre/press-releases/2018/us-fda-grants-fasenra-orphan-drug-designation-for-eosinophilic-granulomatosis-with-polyangiitis-26112018.html.
[Last accessed: September 2023].
12.
Clinicaltrials.gov. Efficacy and Safety of Benralizumab in Moderate
to Very Severe Chronic Obstructive Pulmonary Disease (COPD) With a
History of Frequent Exacerbations (RESOLUTE). Available from:
https://clinicaltrials.gov/ct2/show/NCT04053634. [Last accessed:
September 2023].
13.
Clinicaltrials.gov. Efficacy and Safety Study of Benralizumab in
Patient With Eosinophilic Chronic Rhinosinusitis With Nasal Polyps
(ORCHID). Available at:
https://clinicaltrials.gov/ct2/show/NCT04157335. [Last accessed:
September 2023].
14.
Clinicaltrials.gov. A Phase 3 Study to Evaluate the Efficacy and
Safety of Benralizumab in Patients With Hypereosinophilic Syndrome
(HES) (NATRON). Available from:
https://clinicaltrials.gov/ct2/show/NCT04191304. [Last accessed:
September 2023].
15.
AstraZeneca Data on file. 2022.
REF-167820.
16. Bell CF, et al. Burden of illness and
costs associated with eosinophilic granulomatosis with
polyangiitis: evidence from a managed care database in the United
States. J Manag Care Spec
Pharm.
2021;27:1249-1259.
17.
AstraZeneca Data on file. 2023. REF-196096.
18. Bleecker ER, et al. Efficacy and safety
of benralizumab for patients with severe asthma uncontrolled with
high-dosage inhaled corticosteroids and long-acting b 2-agonists
(SIROCCO): a randomised, multicentre, placebo-controlled phase 3
trial. Lancet. 2016;388:2115-2127.
19. FitzGerald JM, et al. Benralizumab, an
anti-interleukin-5 receptor a monoclonal antibody, as add-on
treatment for patients with severe, uncontrolled, eosinophilic
asthma (CALIMA): a randomised, double-blind, placebo-controlled
phase 3 trial. Lancet. 2016;388:2128-2141.
20. Nair P, et al. Oral
Glucocorticoid-Sparing Effect of Benralizumab in Severe
Asthma. N Engl J
Med.
2017;376:2448-2458.
21. Menzies-Gow A, et al. Oral
corticosteroid elimination via a personalised reduction algorithm
in adults with severe, eosinophilic asthma treated with
benralizumab (PONENTE): a multicentre, open-label, single-arm
study.
Lancet Respir Med.
2022;10:47-58.
22. Harrison
TW, et al. Onset of effect and impact on health-related quality of
life, exacerbation rate, lung function, and nasal polyposis
symptoms for patients with severe eosinophilic asthma treated with
benralizumab (ANDHI): a randomised, controlled, phase 3b
trial. Lancet Respir
Med.
2021;9:260-274.
Adrian Kemp
Company Secretary
AstraZeneca PLC
SIGNATURES
Pursuant
to the requirements of the Securities Exchange Act of 1934, the
Registrant has duly caused this report to be signed on its behalf
by the undersigned, thereunto duly authorized.
Date:
11 September 2023
|
By: /s/
Adrian Kemp
|
|
Name:
Adrian Kemp
|
|
Title:
Company Secretary
|