VERTEX PHARMACEUTICALS INC / MA

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

SCHEDULE 14A

Proxy Statement Pursuant to Section 14(a) of the Securities Exchange Act of 1934

x Filed by the Registranto Filed by a Party other than the Registrant

Vertex Pharmaceuticals Incorporated

(Name of Registrant as Specified In Its Charter)

A Letter from our Executive Chairman andChief Executive Officer

Dear Shareholders:

Our strategy is grounded in the conviction that a sustained, disciplined focus on serial innovation – aimed at delivering

transformative medicines for serious diseases with high unmet need – creates enduring value for patients and shareholders.

That conviction was clearly demonstrated in 2025 through strong commercial performance, meaningful pipeline progress,

and robust financial results.

In 2025, we added to our increasingly diversified commercial portfolio by successfully launching JOURNAVX in acute pain,

our fourth commercialized disease area. In cystic fibrosis, we launched ALYFTREK, which builds upon TRIKAFTA by

providing the best CFTR protein function restoration of any of our approved medicines, while also demonstrating efficacy in

additional mutations and allowing for once-daily dosing. In addition, we accelerated adoption of and built significant

momentum for CASGEVY in the U.S., Europe, and the Middle East. Importantly, we also began preparing for the anticipated

near-term commercialization of povetacicept in IgA nephropathy, the first product in our rapidly advancing renal pipeline. We

believe our emerging renal franchise – alongside CF, heme and pain – will be a key driver for Vertex’s next period of growth.

On the research and development front, our differentiated strategy has delivered a broad, deep, and advanced pipeline that

has the potential to deliver more transformative medicines. In addition to the ongoing Phase 3 study of povetacicept in IgA

nephropathy, we have four other programs in pivotal development: inaxaplin for APOL1-mediated kidney disease, suzetrigine

for diabetic peripheral neuropathy, zimislecel for type 1 diabetes, and povetacicept for primary membranous nephropathy.

Our earlier stage pipeline is also making strong progress with multiple programs advancing in the proof-of-concept stage:

VX-407 in autosomal dominant polycystic kidney disease, VX-670 in myotonic dystrophy type-1, and povetacicept in

generalized myasthenia gravis.

From a revenue perspective, our total revenues in 2025 were$12 billion, led by cystic fibrosis and with increasing

contributions from CASGEVY and an incremental contribution from the first year of the JOURNAVX launch. Our balance sheet

remains robust and we continue to invest significantly in internal and external innovation to support our differentiated

research and development approach, as well as in the ongoing diversification of our commercialization efforts.

In addition to our business achievements, we remain deeply committed to making a positive impact in the communities

where we live and work. During our annual Week of Service, 83% of Vertex employees around the world contributed more

than 11,800 volunteer hours, impacting the lives of over 64,000 individuals. Vertex and The Vertex Foundation also awarded

approximately $51 million in donations to support initiatives that advance education, health, social innovation, and our

communities. We are also honored that Vertex continued to be recognized as an excellent place to work, receiving

accolades such as Fortune 100 Best Companies to Work For, TIME 100 Most Influential Companies, and U.S. News & World

Report Best Companies to Work For.

It is an exciting time for Vertex. With our leadership in cystic fibrosis, the strength of our products and pipeline, and our

strong financial profile, we are well positioned to deliver on the significant opportunities ahead and to drive sustained growth

over the long term. As Executive Chairman and Chief Executive Officer, we are committed to disciplined execution of our

commercial priorities, driving our serial innovation strategy, and delivering transformative medicines to patients.

Sincerely,

Jeffrey M. Leiden, M.D., Ph.D.

Executive Chairman

Reshma Kewalramani, M.D.

Chief Executive Officer and President

NOTICE OF ANNUAL MEETING OF SHAREHOLDERS

Wednesday, May 13, 2026

9:00 a.m. (Eastern Time)

https://meetnow.global/MMMVT4H

Dear Shareholders:

You are invited to attend the Vertex Pharmaceuticals Incorporated 2026 Annual Meeting of Shareholders. At the annual

meeting, shareholders will vote:

•to elect the eleven director nominees that are set forth in the attached proxy statement to our board of directors to serve for a one-

year term until the 2027 annual meeting of shareholders and until such person’s successor has been duly elected and qualified;

•to ratify the selection of Ernst & Young LLP as our independent registered public accounting firm for 2026;

•to hold an advisory vote on our 2025 named executive officer compensation;

•to approveour 2026 Stock and Option Plan; and

•on one proposal submitted by a shareholder, if properly presented at the meeting.

Shareholders also will transact any other business that may properly come before the annual meeting or any adjournment or

postponement of the annual meeting.

PROXY MATERIALS:

We are using the “Notice and Access” method of providing proxy materials to you via the Internet. We are mailing to you a Notice of

Internet Availability of Proxy Materials instead of paper copies of this notice, our proxy statement, and our Annual Report on Form 10-K

for the year ended December 31,2025 (“Annual Report”). Notice and Access provides a convenient way for you to access our proxy

materials. The Notice of Internet Availability of Proxy Materials includes instructions on how to access this notice, our proxy statement,

and our Annual Report and how to vote your shares. The Notice of Internet Availability of Proxy Materials also contains instructions on

how to receive a paper copy of the proxy materials and our Annual Report, if you prefer.

MEETING ACCESS:

THE ANNUAL MEETING WILL BE HELD VIRTUALLY VIA WEBCAST. A VIRTUAL ANNUAL MEETING WILL FACILITATE

SHAREHOLDER ATTENDANCE AND PARTICIPATION BY ENABLING SHAREHOLDERS TO PARTICIPATE FROM ANY

LOCATION AND AT NO COST. YOU WILL BE ABLE TO PARTICIPATE IN THE MEETING ONLINE, VOTE YOUR SHARES

ELECTRONICALLY, AND SUBMIT YOUR QUESTIONS DURING THE MEETING BY VISITING HTTPS://MEETNOW.GLOBAL/

MMMVT4H. THERE IS NO PHYSICAL LOCATION FOR THE ANNUAL MEETING.

Shareholders will need their unique control number, which appears on the Notice of Internet Availability of Proxy Materials or proxy card

(printed in the shaded bar), or within the body of the email sending the proxy statement. If you hold shares beneficially through a bank,

broker or other nominee (that is, in “street name”), you must register in advance togain access to the virtual meeting and to vote shares

electronically during the meeting. To register, you will need to obtain a legal proxy from your bank, broker or other nominee. Once you

have received a legal proxy from them, you must submit a copy of this legal proxy, along with your name and email address to

Computershare at legalproxy@computershare.com. Alternatively, you may mail your legal proxy to the following address:

Computershare, Vertex Pharmaceuticals Incorporated Legal Proxy, P.O. Box 43001, Providence, RI 02940-3001. Requests for

registration must be labeled as “Legal Proxy” and received no later than 5:00 p.m. (Eastern Time) on May 8, 2026. You will receive an

email from Computershare confirming your registration and providing your control number. You will need your control number toaccess

the virtual annual meeting, submit your questions and vote your shares electronically.

The annual meeting will begin promptly at 9:00 a.m. (Eastern Time) on May 13, 2026.

We will make a list of our shareholders of record available electronically during the annual meeting. A shareholder wishing access to

the list during the annual meeting should contact our corporate secretary in advance of the meeting.

RECORD DATE:

Only Vertex Pharmaceuticals Incorporated shareholders of record at the close of business on March 16, 2026 are entitled to receive

notice of, and vote at, the annual meeting, and, subject to applicable law, any adjournment or postponement thereof.

VOTING:

Your vote matters. Whether or not you plan to attend the annual meeting, we urge you to vote as promptly as possible by Internet,

telephone or signing, dating and returning a printed proxy card. If you attend the annual meeting, you may vote your shares during the

annual meeting even if you previously voted your proxy. Please vote as soon as possible to ensure that your shares will be represented

and counted at the annual meeting.

April 2, 2026

By Order of the Board of Directors,

Joy LiuChief Legal Officer

IMPORTANT NOTICE REGARDING INTERNET AVAILABILITY OF PROXY MATERIALS. This notice, our proxy statement, and our Annual Report on Form 10-K for the year ended December 31, 2025 are first being made available to holders of record of our common stock on or about April 2, 2026. These materials are available to holders of record of our common stock at www.envisionreports.com/VRTX and to beneficial holders of our common stock at www.edocumentview.com/VRTX.

TABLE OF CONTENTS

PROXY STATEMENT

This proxy statement is being made available to shareholders of Vertex Pharmaceuticals Incorporated (“Vertex”) in connection with the

solicitation by our board of directors of proxies to be voted at our 2026 annual meeting of shareholders and at any postponement or

adjournment thereof. The annual meeting will be held on Wednesday, May 13, 2026, at 9:00 a.m. (Eastern Time) as a virtual meeting

conducted exclusively via live webcast athttps://meetnow.global/MMMVT4H. See Frequently Asked Questions Regarding the Annual

Meeting - How May I Attend the Annual Meeting? below for information regarding attending the virtual annual meeting.