Income Taxes, Reconciliation of Statutory to Effective Tax Rate (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2020	Dec. 31, 2019	Dec. 31, 2018
Reconciliation Between Effective and Statutory Tax Rate [Abstract]
Pre-tax income (loss)	$ (170,032)	$ 346,769	$ (76,156)
Statutory rate	(35,707)	72,822	(15,993)
State income tax net of federal benefit	(39,230)	49,119	(2,202)
Foreign	49	340	1,735
Net change in valuation allowance	437,597	(37,765)	(277,924)
Net operating loss expiration	0	0	8,864
TEGSEDI licensing gain	0	0	59,583
Impact from outside basis differences	0	(16,344)	0
Tax credits	(18,774)	(22,296)	(73,362)
Deferred tax true-up	(206)	646	9,947
Tax rate change	(29,131)	1,811	(1,808)
Non-deductible compensation	7,931	3,361	3,154
Other non-deductible items	193	329	(569)
Stock-based compensation	17,435	(4,837)	(4,199)
Foreign-derived intangible income benefit	0	(2,071)	0
Impacts from Akcea Acquisition	(22,032)	0	0
Other	(1,391)	(1,608)	1,633
Total income tax expense (benefit)	$ 316,734	$ 43,507	$ (291,141)
Reconciliation Between Effective and Statutory Tax Rate Percentage [Abstract]
Statutory rate	21.00%	21.00%	21.00%
State income tax net of federal benefit	23.10%	14.20%	2.90%
Foreign	0.00%	0.10%	(2.30%)
Net change in valuation allowance	(257.40%)	(10.90%)	364.90%
Net operating loss expiration	0.00%	0.00%	(11.60%)
TEGSEDI licensing gain	0.00%	0.00%	(78.20%)
Impact from outside basis differences	0.00%	(4.70%)	0.00%
Tax credits	11.00%	(6.40%)	96.30%
Deferred tax true-up	0.10%	0.20%	(13.10%)
Tax rate change	17.10%	0.50%	2.40%
Non-deductible compensation	(4.70%)	1.00%	(4.10%)
Other nondeductible items	(0.10%)	0.10%	0.70%
Stock-based compensation	(10.30%)	(1.40%)	5.50%
Foreign-derived intangible income benefit	0.00%	(0.60%)	0.00%
Impacts from Akcea Acquisition	13.00%	0.00%	0.00%
Other	0.80%	(0.50%)	(2.10%)
Effective rate	(186.40%)	12.60%	382.30%