Share-Based Payments - Stock-Based Compensation Expense for Employee and Non-Employee Stock Options, Restricted Stock Units, Performance-Based Stock Options, Performance-Based Stock Units and Employee Stock Purchase Plan Shares (Details) - USD ($) $ in Thousands	12 Months Ended
	Dec. 31, 2017	Dec. 31, 2016	Dec. 31, 2015
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Allocated share based compensation expense	$ 47,809	$ 42,086	$ 31,963
Research and development expense
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Allocated share based compensation expense	30,807	25,386	17,419
General and administrative expense
Share-based Compensation Arrangement by Share-based Payment Award [Line Items]
Allocated share based compensation expense	$ 17,002	$ 16,700	$ 14,544