Amendment No. 1 to Employment Agreement, between Jeffrey M. Leiden and Vertex

This AMENDMENT NO. 1 is made and entered into effective as of February 7, 2022 (the “Effective Date”) to the employment agreement dated as of April 1, 2020 (the “Employment Agreement”), between Vertex Pharmaceuticals Incorporated (the “Company”) and Jeffrey M. Leiden, MD., Ph.D. (the “Executive”).

“(c) Equity Awards. During the Term of this Agreement, and provided that the Executive has remained in continuous service with the Company through the applicable grant date, subject to the approval of the Board or the Compensation Committee thereof, the Executive will receive the following annual grants of equity awards (the “Annual Stock Awards”). Each Annual Stock Award will be made during the applicable time period set forth below. Fifty percent (50%) of each Annual Stock Award will be in the form of fully vested shares of Company common stock and fifty percent (50%) will be in the form of performance stock units and the Annual Stock Award will have an aggregate grant date value (with performance stock units valued based on target, and the number of shares or units granted, as applicable, determined by dividing such values by the fair market value of the Company’s common stock) as follows:

(i)$9,000,000 for fiscal year 2020 (to be granted in the first calendar quarter of 2021) (“Year 1”);

(ii)$8,500,000 for fiscal year 2021 (to be granted in the first calendar quarter of 2022) (“Year 2”);

(iii)$6,500,000 for fiscal year 2022 (to be granted in the first calendar quarter of 2023) (“Year 3”); and

(iv)$6,500,000 for fiscal year 2023 (to be granted in the first calendar quarter of 2024) (“Year 4”).

Both one-year and three-year performance criteria will apply to the performance stock units granted in Year 1, and one-year performance criteria will apply to the performance stock units granted in Year 2, Year 3 and Year 4. The terms and conditions applicable to each Annual Stock Award shall otherwise be as prescribed by the Compensation Committee, with each Annual Stock Award evidenced by an award agreement that is substantially similar to the form of award agreement used for such type of award for Company executives generally, except for such changes as are necessary or desirable to reflect the terms of the Executive’s employment hereunder.”

4.That Section 4(d) of the Employment Agreement is hereby amended adding a final sentence to such Section as follows:

“In order to facilitate the Executive’s receipt of benefits under the Employee Benefit Plans in 2022, 2023 and 2024, the Company will make a cash payment to executive of $65,000 in each of February 2022, February 2023 and February 2024.”

5.Except as amended hereby and expressly provided herein, the Employment Agreement shall remain in full force and effect.

    IN WITNESS WHEREOF, this Amendment No. 1 has been executed as a sealed instrument by the Company, by its duly authorized representative, and by the Executive, as of the date first above written.