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Income taxes (Details 5) - USD ($) $ in Thousands | 12 Months Ended
--- | ---
Dec. 31, 2016 | Dec. 31, 2015 | Dec. 31, 2014
Operating loss carryforwards |  |  |
Valuation allowance | $ 183,015 | $ 139,584 |
Valuation allowance, deferred tax asset, increase (decrease) | (43,400) | $ 16,300 |
Orphan drug credit carryover | 60,100 |  |
Limited NOL carryforwards | 231,500 |  |
Operating loss carryforwards, not subject to expiration | $ 169,200 |  |
NOL carryforward period | 20 years |  |
Operating loss carryforwards, subject to expiration | $ 62,300 |  |
Operating loss carryforwards for immediate use | 175,100 |  |
Operating loss carryforwards in next twelve months | $ 16,700 |  |
Federal income tax (benefit) at statutory rate (as a percent) | 34.00% | 34.00% | 34.00%
Uncertain tax position | $ 0 |  |
First five years from ownership change |  |  |
Operating loss carryforwards |  |  |
Net operating loss carryforwards | 16,700 |  |
After five years |  |  |
Operating loss carryforwards |  |  |
Net operating loss carryforwards | 5,700 |  |
Federal |  |  |
Operating loss carryforwards |  |  |
Net operating loss carryforwards | 285,800 |  |
Operating loss carryforwards associated to exercise of stock options and vesting of restricted stock | 50,400 |  |
Tax benefit related to operating loss carryforwards | 17,100 |  |
Research and development credit carryforwards | 14,400 |  |
State |  |  |
Operating loss carryforwards |  |  |
Net operating loss carryforwards | 213,200 |  |
Research and development credit carryforwards | $ 7,300 |  |

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