Income Taxes (Tables)

12 Months Ended

Dec. 31, 2021

Income Tax Disclosure [Abstract]

Summary of (Loss) Income Before Provision (Benefit) for Income Taxes by Region

The following table summarizes the Company’s (loss) income before income taxes by region for the years presented, in thousands:

	Years ended December 31,
	2021		2020		2019
United States	$	(570,860)	$	(386,292)	$	298,315
Foreign	(45,573)		(18,442)		209,573
Total (loss) income before income taxes	$	(616,433)	$	(404,734)	$	507,888

Reconciliation of Provision (Benefit) for Income Taxes at Statutory Federal Rate to Provision (Benefit) for Income Taxes

The Company’s effective income tax rate differs from the statutory federal rate of 21% for 2021, 2020 and 2019 due to the following, in thousands:

	Years ended December 31,
	2021		2020		2019
(Benefit) Provision for income taxes at statutory federal rate	$	(129,451)	$	(84,994)	$	106,657
Change in federal and foreign valuation allowance	173,118		101,091		34,712
Deferred adjustment related to foreign net operating losses	—		—		15,133
Capital loss on foreign subsidiary liquidation	—		—		(43,685)
State Tax, net of federal benefit	(38,323)		(4,837)		592
Share-based compensation expense	(1,114)		(5,906)		1,624
Foreign losses at lower effective rates	8,400		3,856		21
Research and development and Orphan Drug credits	(13,744)		(9,617)		(4,730)
Permanent differences and other	1,114		407		9
Provision for income taxes	$	—	$	—	$	110,333

Components of Net Deferred Tax Assets

The components of the Company’s net deferred tax assets are as follows, in thousands:

	December 31,
	2021		2020
Deferred tax assets:
Federal and California NOL carryforwards	$	371,499	$	230,994
Federal and California research and development credit carryforwards	97,548		83,589
Foreign NOL carryforwards	977		472
Share-based compensation expense	16,718		13,572
Depreciation	3,250		3,015
Lease liability	1,922		2,200
Other, net	17,596		1,217
Total deferred tax assets	509,510		335,059
Deferred tax liabilities:
Right-of-use assets	(1,777)		(2,051)
Equity investment	(4,119)		(2,512)
Total deferred tax liabilities	(5,896)		(4,563)
Net deferred tax assets	503,614		330,496
Valuation allowance	(503,614)		(330,496)
Net deferred tax assets	$	—	$	—

Reconciliation of Unrecognized Tax Benefits

The following table reconciles the beginning and ending amount of unrecognized tax benefits for the years presented, in thousands:

	Years ended December 31,
	2021		2020		2019
Gross unrecognized tax benefits at the beginning of the year	$	11,710	$	9,954	$	9,033
Additions from tax positions taken in the current year	2,555		1,706		1,017
Additions from tax positions taken in prior years	12		50		—
Reductions from tax positions taken in prior years	—		—		(96)
Gross unrecognized tax benefits at end of the year	$	14,277	$	11,710	$	9,954