VRTXVertex Pharmaceuticals

We note your disclosure stating that you entered into collaboration agreements with Zai Lab Limited and Ono Pharmaceuticals Co. Ltd. In future filings, if material, please expand your disclosure to describe the material terms of these agreements including, but not limited to, the termination provisions and any royalty or milestone payment requirements. Disclose the royalty rate or a range not exceeding 10%.

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In addition, tell us how you considered whether to file the agreements as exhibits.

The Company acknowledges the Staff’s comment, and respectfully advises the Staff that the Company has concluded that its agreements with

Zai Lab Limited (the “Zai Agreement”) and Ono Pharmaceuticals Co., Ltd. (the “Ono Agreement,” and together with the Zai Agreement, the “Agreements”), while beneficial, are not material to the Company and, therefore, are not required to be filed as exhibits to the Company’s filings with the Commission, including the 2025 10-K, pursuant to Item 601(b)(10) of Regulation

S-K.

The Company reached this conclusion based on the following primary

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considerations:

•

Immaterial financial value. The upfront consideration paid to the Company and potential future payments that may be paid to the Company under each Agreement are de minimis relative to the Company’s 2025 total revenue of $12.0 billion and anticipated future total revenues. In 2025, the Company received upfront payments of $10.0 million and $20.6 million under the Zai Agreement and Ono Agreement, respectively. Similarly, the potential future milestone and royalty payments to the Company, if povetacicept is successfully developed in the territories subject to these Agreements, are not anticipated to be material to the Company’s annual revenues.

Limited geographic scope. Each Agreement covers discrete, geographic territories in Asia, outside the

Company’s principal markets of the United States and European Union. Potential future royalties from sales within the territories subject to the Agreements, if any, would represent a fraction of the Company’s global commercial opportunity.

If the Company concludes in the future that either Agreement is material, the Company will disclose material terms of such Agreement, including termination provisions and royalty rate ranges not exceeding 10%, and will file such Agreement as required by the applicable securities laws.

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We note your disclosure that ALYFTREK carries a lower royalty burden than your other CF medicines. However, we also note from your disclosure on page 58 that there may be uncertainty regarding the calculations of royalties that you will pay on ALYFTREK to a third-party under the agreement with the Cystic Fibrosis Foundation and that you could be required to pay a higher royalty percentage on ALYFTREK sales than you

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currently expect. If you expect patients to switch from TRIKAFTA to ALYFTREK, please quantify in your future filings your current royalty burden on TRIKAFTA, your primary CF medicine, and, given the uncertainty described on page 58, provide an upper and lower bounded range of the royalty burden on ALYFTREK depending on the outcome of the calculations of the royalties that will be payable on ALYFTREK. Cystic Fibrosis Foundation, page 15 We note your collaboration agreement with the Cystic Fibrosis Foundation results in the payment of a material amount of royalties. We also note your disclosure that, 2. pursuant to the agreement, sales of combination products, such as TRIKAFTA/KAFTRIO, are allocated equally to each of the active pharmaceutical ingredients in the combination product, and royalties are then paid for any royaltybearing components included in the combination. In future filings, place revise to disclose the duration of the royalty terms associated with the active pharmaceutical ingredients in your material combination products, such as TRIKAFTA/KAFTRIO, pursuant to this collaboration agreement.

The Company respectfully acknowledges the Staff’s comment and will provide responsive disclosure in future filings. Read in the reply ↗

Please expand your discussion of the reasons you believe that your leadership structure is appropriate, addressing your specific characteristics or circumstances. In your discussion, please also address the circumstances under which you would consider having the Chair and CEO roles filled by a single individual, when shareholders would be notified of any such change, and whether you will seek prior input from

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shareholders. Please also address how the experience of your Lead Independent Director is brought to bear in connection with your board’s role in risk oversight.

The Company acknowledges the Staff’s comment, and will enhance its future proxy disclosures to expand its discussion of the reasons it believes its leadership structure is appropriate. The discussion will address, among other matters, the circumstances under which the Company would consider having the Chair and CEO roles filled by a single individual, when shareholders would be notified of any such change, and whether the Company will seek prior input from its shareholders.

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The discussion will also address how the experience of the Company’s Lead Independent Director is brought to bear in connection with the board’s role in risk oversight.

Securities and Exchange Commission

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Please expand upon the role that your Lead Independent Director plays in the leadership of the board. For example, please enhance your disclosure to address whether or not your Lead Independent Director may: • represent the board in communications with shareholders and other stakeholders; • require board consideration of, and/or override your CEO on, any risk matters; or • provide input on design of the board itself.

The Company acknowledges the Staff’s comment, and will enhance its future proxy disclosures to expand its discussion of the role its Lead Independent Director plays in the leadership of the board. The disclosure will address, among other matters, whether or not its Lead Independent Director may: (i) represent the board in communications with shareholders or other stakeholders, (ii) require board consideration of, and/or override the Company’s CEO on, any risk matters, and

(iii) provide input on the design of the board itself. Read in the reply ↗

Please expand upon how your board administers its risk oversight function. For example, please disclose: • the timeframe over which you evaluate risks (e.g., short-term, intermediate-term, or long-term) and how you apply different oversight standards based upon the immediacy of the risk assessed; • whether you consult with outside advisors and experts to anticipate future threats and trends, and how often you

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re-assess your risk environment; • whether you have a Chief Compliance Officer and to whom this position reports; and • how your risk oversight process aligns with your disclosure controls and procedure.

acknowledges the Staff’s comment, and will enhance its future proxy disclosures to expand upon how its board administers its risk oversight function. The disclosures will address, among other matters, the timeframe over which the Company evaluates risks and how its applies different oversight standards based upon the immediacy of the risks assessed, whether it consults with outside advisors and experts to anticipate future threats and trends and how often it re-assesses its risk environment, whether it has a Chief Compliance Officer and to whom this position reports, and how its risk

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oversight process aligns with its disclosure controls and procedures.

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