Income Taxes, Reconciliation of Statutory to Effective Tax Rate (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2021	Dec. 31, 2020	Dec. 31, 2019
Reconciliation Between Effective and Statutory Tax Rate [Abstract]
Pre-tax income (loss)	$ (29,148)	$ (134,552)	$ 338,766
Statutory rate	(6,121)	(28,256)	71,141
State income tax net of federal benefit	4,278	(37,705)	49,000
Foreign	143	49	340
Net change in valuation allowance	2,885	460,898	(37,314)
Loss on debt transactions	262	0	9,911
Impact from outside basis differences	0	0	(16,344)
Tax credits	(23,198)	(18,774)	(22,296)
Deferred tax true-up	(24)	(206)	646
Tax rate change	12,838	(32,951)	1,248
Non-deductible compensation	5,085	7,931	3,361
Other non-deductible items	84	193	329
Stock-based compensation	4,720	17,435	(4,837)
Foreign-derived intangible income benefit	0	0	(2,071)
Impacts from Akcea Merger	0	(22,032)	0
Other	(1,503)	(1,391)	(1,607)
Total income tax expense (benefit)	$ (551)	$ 345,191	$ 51,507
Reconciliation Between Effective and Statutory Tax Rate Percentage [Abstract]
Statutory rate	21.00%	21.00%	21.00%
State income tax net of federal benefit	(14.70%)	28.00%	14.50%
Foreign	(0.50%)	0.00%	0.10%
Net change in valuation allowance	(9.90%)	(342.50%)	(11.00%)
Loss on debt transactions	(0.90%)	0.00%	2.90%
Impact from outside basis differences	0.00%	0.00%	(4.80%)
Tax credits	79.60%	14.00%	(6.60%)
Deferred tax true-up	0.10%	0.20%	0.20%
Tax rate change	(44.00%)	24.50%	0.40%
Non-deductible compensation	(17.40%)	(5.90%)	1.00%
Other nondeductible items	(0.30%)	(0.10%)	0.10%
Stock-based compensation	(16.20%)	(13.00%)	(1.40%)
Foreign-derived intangible income benefit	0.00%	0.00%	(0.60%)
Impacts from Akcea Merger	0.00%	16.40%	0.00%
Other	5.10%	0.90%	(0.60%)
Effective rate	1.90%	(256.50%)	15.20%