Income Taxes, Reconciliation of Statutory to Effective Tax Rate (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2022	Dec. 31, 2021	Dec. 31, 2020
Reconciliation Between Effective and Statutory Tax Rate [Abstract]
Pre-tax income (loss)	$ (257,985)	$ (29,148)	$ (134,552)
Statutory rate	(54,177)	(6,121)	(28,256)
State income tax net of federal benefit	(13,622)	4,278	(37,705)
Foreign	(49)	143	49
Net change in valuation allowance	104,951	2,885	460,898
Loss on debt transactions	0	262	0
Tax credits	(39,729)	(23,198)	(18,774)
Deferred tax true-up	(20)	(24)	(206)
Tax rate change	(3,091)	12,838	(32,951)
Non-deductible compensation	3,023	5,085	7,931
Other non-deductible items	57	84	193
Stock-based compensation	14,030	4,720	17,435
Impacts from Akcea Merger	0	0	(22,032)
Other	364	(1,503)	(1,391)
Total income tax expense (benefit)	$ 11,737	$ (551)	$ 345,191
Reconciliation Between Effective and Statutory Tax Rate Percentage [Abstract]
Statutory rate	21.00%	21.00%	21.00%
State income tax net of federal benefit	5.30%	(14.70%)	28.00%
Foreign	0.00%	(0.50%)	0.00%
Net change in valuation allowance	(40.70%)	(9.90%)	(342.50%)
Loss on debt transactions	0.00%	(0.90%)	0.00%
Tax credits	15.40%	79.60%	14.00%
Deferred tax true-up	0.00%	0.10%	0.20%
Tax rate change	1.20%	(44.00%)	24.50%
Non-deductible compensation	(1.20%)	(17.40%)	(5.90%)
Other non-deductible items	0.00%	(0.30%)	(0.10%)
Stock-based compensation	(5.40%)	(16.20%)	(13.00%)
Impacts from Akcea Merger	0.00%	0.00%	16.40%
Other	(0.10%)	5.10%	0.90%
Effective rate	(4.50%)	1.90%	(256.50%)