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Income Taxes, Reconciliation of Statutory to Effective Tax Rate (Details) - USD ($) $ in Thousands | 12 Months Ended
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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%

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- Definition The amount of income tax expense or benefit for the period computed by applying the domestic federal statutory tax rates to pretax income from continuing operations. + References Reference 1: http://www.xbrl.org/2003/role/disclosureRef -Publisher FASB -Name Accounting Standards Codification -Topic 740 -SubTopic 10 -Section 50 -Paragraph 12 -URI http://asc.fasb.org/extlink&oid=121826272&loc=d3e32687-109319 + Details
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- Definition Amount of the difference between reported income tax expense (benefit) and expected income tax expense (benefit) computed by applying the domestic federal statutory income tax rates to pretax income (loss) from continuing operations attributable to other nondeductible expenses. + References Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef -Publisher FASB -Name Accounting Standards Codification -Topic 740 -SubTopic 10 -Section 50 -Paragraph 12 -URI http://asc.fasb.org/extlink&oid=121826272&loc=d3e32687-109319 + Details
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- Definition Amount of reported income tax expense (benefit) in excess of (less than) expected income tax expense (benefit) computed by applying domestic federal statutory income tax rate to pretax income (loss) from continuing operation, attributable to nondeductible expense for award under share-based payment arrangement. Includes, but is not limited to, expense determined to be nondeductible upon grant or after for award under share-based payment arrangement. + References Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef -Publisher FASB -Name Accounting Standards Codification -Topic 740 -SubTopic 10 -Section 50 -Paragraph 12 -URI http://asc.fasb.org/extlink&oid=121826272&loc=d3e32687-109319 + Details
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- Definition Amount of the difference between reported income tax expense (benefit) and expected income tax expense (benefit) computed by applying the domestic federal statutory income tax rates to pretax income (loss) from continuing operations attributable to other adjustments. + References Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef -Publisher FASB -Name Accounting Standards Codification -Topic 740 -SubTopic 10 -Section 50 -Paragraph 12 -URI http://asc.fasb.org/extlink&oid=121826272&loc=d3e32687-109319 + Details
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- Definition Amount of the difference between reported income tax expense (benefit) and expected income tax expense (benefit) computed by applying the domestic federal statutory income tax rates to pretax income (loss) from continuing operations attributable to revisions of previously reported income tax expense (benefit). + References Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef -Publisher FASB -Name Accounting Standards Codification -Topic 740 -SubTopic 10 -Section 50 -Paragraph 12 -URI http://asc.fasb.org/extlink&oid=121826272&loc=d3e32687-109319 + Details
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- Definition Amount of the difference between reported income tax expense (benefit) and expected income tax expense (benefit) computed by applying the domestic federal statutory income tax rates to pretax income (loss) from continuing operations attributable to state and local income tax expense (benefit). + References Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef -Publisher FASB -Name Accounting Standards Codification -Topic 740 -SubTopic 10 -Section 50 -Paragraph 12 -URI http://asc.fasb.org/extlink&oid=121826272&loc=d3e32687-109319 + Details
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- Definition Amount of the difference between reported income tax expense (benefit) and expected income tax expense (benefit) computed by applying the domestic federal statutory income tax rates to pretax income (loss) from continuing operations attributable to tax credits. Including, but not limited to, research credit, foreign tax credit, investment tax credit, and other tax credits. + References Reference 1: http://www.xbrl.org/2009/role/commonPracticeRef -Publisher FASB -Name Accounting Standards Codification -Topic 740 -SubTopic 10 -Section 50 -Paragraph 12 -URI http://asc.fasb.org/extlink&oid=121826272&loc=d3e32687-109319 + Details
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