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Shareholders’ Equity (Tables)
 12 Months Ended
Dec. 31, 2018
Disclosure of Compensation Related Costs, Share-based Payments [Abstract]  
Summary of Stock Option Activity and Related Data
The Company’s stock option activity under its option plans was comprised of the following:
 
Outstanding Stock Options and 2013 Equity Plan
 
Shares
Underlying
Stock Options
 
Weighted-
average
Exercise Price
per Share
 
Weighted-
average
Remaining
Contractual
Term
 
Aggregate
Intrinsic
Value
Outstanding at December 31, 2015
2,318,685

 
$
22.01

 
 
 
 
Granted
483,200

 
$
17.83

 
 
 
 
Exercised
(17,548
)
 
$
8.52

 
 
 
 
Forfeited
(156,875
)
 
$
26.35

 
 
 
 
Outstanding at December 31, 2016
2,627,462

 
$
21.07

 
 
 
 
Granted
3,704,725

 
$
25.94

 
 
 
 
Exercised
(174,628
)
 
$
15.42

 
 
 
 
Forfeited
(120,257
)
 
$
22.82

 
 
 
 
Outstanding at December 31, 2017
6,037,302

 
$
24.19

 
 
 
 
Granted
1,978,219

 
$
23.66

 
 
 
 
Exercised
(106,370
)
 
$
17.95

 
 
 
 
Forfeited
(1,442,937
)
 
$
28.07

 
 
 
 
Outstanding at December 31, 2018
6,466,214

 
$
23.26

 
7.65 years
 
$
200,279

Vested and expected to vest at December 31, 2018
6,466,214

 
$
23.26

 
7.65 years
 
$
200,279

Exercisable at December 31, 2018
3,118,365

 
$
22.61

 
6.33 years
 
$
200,279
Summary of restricted stock activity
The Company’s RSA activity was comprised of the following:
 
Number of
Shares
 
Weighted-
average Grant
Date Fair
Market Value
Unvested at December 31, 2015
1,072,899

 
$
13.00

Vested
(530,219
)
 
$
12.78

Unvested at December 31, 2016
542,680

 
$
13.22

Vested
(542,680
)
 
$
13.22

Unvested at December 31, 2017
—

 
—
Stock Options, Valuation Assumptions
estimates the fair value of each stock option grant on the grant date using the Black-Scholes model with the following weighted-average assumptions:
 
Year Ended December 31,
 
2018
 
2017
 
2016
Volatility
114
%
 
139
%
 
143
%
Expected life (years)
6.07

 
6.12

 
5.80

Risk-free interest rate
2.8
%
 
2.1
%
 
1.4
%
Dividend yield
—

 
—

 
—
Summary of Share-based Compensation Expense
Total share-based compensation expense related to all share-based awards was comprised of the following (in thousands):
 
Year Ended December 31,
 
2018
 
2017
 
2016
Research and development
$
21,113

 
$
11,980

 
$
5,657

Selling, general and administrative
14,038

 
9,815

 
8,889

Total share-based compensation expense
$
35,151

 
$
21,795

 
$
14,546