Vertex Pharmaceuticals 10-K 2025-12-31

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

WASHINGTON, D.C. 20549

FORM 10-K

**☒**ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934

For the Fiscal Year Ended December 31, 2025

or

**☐**TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934

FOR THE TRANSITION PERIOD FROM TO

Commission file number 000-19319

Vertex Pharmaceuticals Incorporated

(Exact name of registrant as specified in its charter)

Massachusetts

(State or other jurisdiction of incorporation or organization)

50 Northern Avenue**,** Boston**,** Massachusetts

(Address of principal executive offices)

04-3039129

(I.R.S. Employer Identification No.)

02210

(Zip Code)

Registrant’s telephone number, including area code (617) 341-6100

Securities registered pursuant to Section 12(b) of the Exchange Act:

Securities registered pursuant to Section 12(g) of the Exchange Act: None

Indicate by check mark if the registrant is a well-known seasoned issuer, as defined in Rule 405 of the Securities Act. Yes ☒ No ☐

Indicate by check mark if the registrant is not required to file reports pursuant to Section 13 or Section 15(d) of the Exchange Act. Yes ☐ No ☒

Indicate by check mark whether the registrant: (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934 during

the preceding 12 months (or for such shorter period that the registrant was required to file such reports), and (2) has been subject to such filing requirements for

the past 90 days. Yes ☒ No ☐

Indicate by check mark whether the registrant has submitted electronically every Interactive Data File required to be submitted pursuant to Rule 405 of

Regulation S-T (§232.405 of this chapter) during the preceding 12 months (or for such shorter period that the registrant was required to submit such files). Yes ☒

No ☐

Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, a smaller reporting company, or an emerging

growth company. See the definitions of “large accelerated filer,” “accelerated filer,” “smaller reporting company,” and “emerging growth company” in Rule 12b-2

of the Exchange Act (Check one):

Large accelerated filer ☒ Accelerated filer ☐ Non-accelerated filer ☐ Smaller reporting company ☐ Emerging growth company ☐

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or

revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐

Indicate by check mark whether the registrant has filed a report on and attestation to its management’s assessment of the effectiveness of its internal control over

financial reporting under Section 404(b) of the Sarbanes-Oxley Act (15 U.S.C. 7262(b)) by the registered public accounting firm that prepared or issued its audit

report. ☒

If securities are registered pursuant to Section 12(b) of the Act, indicate by check mark whether the financial statements of the registrant included in the filing

reflect the correction of an error to previously issued financial statements. ☐

Indicate by check mark whether any of those error corrections are restatements that required a recovery analysis of incentive-based compensation received by any

of the registrant’s executive officers during the relevant recovery period pursuant to § 240.10D-1(b). ☐

Indicate by check mark whether the registrant is a shell company (as defined in Rule 12b-2 of the Exchange Act). Yes ☐ No ☒

The aggregate market value of the registrant’s common stock held by non-affiliates of the registrant based on the closing price on June 30, 2025 (the last business

day of the registrant’s most recently completed second fiscal quarter of 2025) was $113.4 billion.

As of February 6, 2026, the registrant had 254,034,190 shares of common stock outstanding.

DOCUMENTS INCORPORATED BY REFERENCE

Portions of the definitive proxy statement for the 2026 Annual Meeting of Shareholders, which we expect to hold on May 13, 2026, are incorporated by

reference into Part III of this Annual Report on Form 10-K.

VERTEX PHARMACEUTICALS INCORPORATED

ANNUAL REPORT ON FORM 10-K

TABLE OF CONTENTS

“Vertex,” “we,” “us” and “our” as used in this Annual Report on Form 10-K refer to Vertex Pharmaceuticals

Incorporated, a Massachusetts corporation, and its subsidiaries.

“VERTEX®,” “KALYDECO®,” “ORKAMBI®,” “SYMDEKO®,” “SYMKEVI®,” “TRIKAFTA®,” “KAFTRIO®,”

“CASGEVY®,” “ALYFTREK®,” and “JOURNAVX®” are registered trademarks of Vertex. Other brands, names and

trademarks contained in this Annual Report on Form 10-K are the property of their respective owners.

We use the brand name for our products when we refer to the product that has been approved and with respect to the

indications on the approved label. Otherwise, we refer to our product candidates by their scientific (or generic) name or VX

developmental designation.

This Annual Report on Form 10-K contains forward-looking statements. Words such as “anticipates,” “may,”

“forecasts,” “expects,” “intends,” “plans,” “potentially,” “believes,” “seeks,” “estimates,” variations of such words and

similar expressions are intended to identify such forward-looking statements, although not all forward-looking statements

contain these identifying words. Please refer to “Special Note Regarding Forward-Looking Statements” set forth in Part I,

Item 1A, for a discussion of our forward-looking statements and the related risks and uncertainties of such statements.

PART I

OVERVIEW

We are a global biotechnology company that invests in scientific innovation to create transformative medicines for

people with serious diseases, with a focus on specialty markets. We have approved medicines for cystic fibrosis (“CF”),

sickle cell disease (“SCD”), transfusion dependent beta thalassemia (“TDT”), and acute pain, and we continue to serially

innovate and advance next-generation clinical and research programs in these areas. Our mid- and late-stage clinical pipeline

includes programs across a range of modalities in additional serious diseases, including IgA nephropathy, APOL1-mediated

kidney disease, neuropathic pain, type 1 diabetes, primary membranous nephropathy, autosomal dominant polycystic kidney

disease, and myotonic dystrophy type 1.

The following chart sets forth our approved products, clinical-stage programs, and select pre-clinical programs:

We are advancing five pivotal programs across multiple disease areas:

*•*IgA Nephropathy. We are developing povetacicept, a dual inhibitor of the B cell activating factor (“BAFF”) and a

proliferation-inducing ligand (“APRIL”) pathways, as a potentially best-in-class approach to treat IgA nephropathy

(“IgAN”), a serious, progressive, life-threatening kidney disease that often progresses to end-stage renal disease. We

completed enrollment in the IgAN Phase 3 clinical trial and submitted the first module of the rolling Biologics

Licensing Application (“BLA”) for povetacicept in IgAN in the fourth quarter of 2025. We expect to complete the

submission for potential accelerated approval in the U.S. in the first half of 2026.

• APOL1-Mediated Kidney Disease. We are developing inaxaplin, a small molecule inhibitor of APOL1 as a potential

first-in-class treatment for APOL1-mediated kidney disease (“AMKD”). We have completed the enrollment of the

interim analysis cohort of the Phase 2/3 clinical trial and will conduct the pre-planned interim analysis once this

cohort reaches 48 weeks of treatment. We expect to share data from the interim analysis in late 2026 or early 2027.

*•*Peripheral Neuropathic Pain. We are developing suzetrigine, a selective non-opioid NaV1.8 pain signal inhibitor,

for diabetic peripheral neuropathy (“DPN”), a common form of peripheral neuropathic pain. We are evaluating

suzetrigine for the treatment of DPN in two Phase 3 clinical trials. We expect to complete enrollment in both Phase

3 clinical trials by the end of 2026.

•**Type 1 Diabetes. Zimislecel is an allogeneic stem-cell derived, fully differentiated islet cell therapy in pivotal

development for the treatment of type 1 diabetes (“T1D”). We have completed enrollment in the Phase 1/2/3 clinical

trial of zimislecel in people with T1D. We have temporarily postponed completion of the dosing in this clinical trial,

pending an ongoing internal manufacturing analysis.

*•*Primary Membranous Nephropathy. We are also developing povetacicept to treat primary membranous nephropathy

(“pMN”), a rare and serious autoimmune glomerular disease that can lead to kidney damage and renal failure, and

which has no treatments specifically approved for this condition. We continue to enroll and dose patients in the

adaptive Phase 2/3 pivotal trial in people with pMN. We expect to complete the Phase 2 portion of the clinical trial

and to initiate the Phase 3 portion in mid-2026.

Our core strategy is to discover, develop, and commercialize innovative medicines by combining transformative

advances in the understanding of human disease and the science of therapeutics, to dramatically advance human health. We

focus on validated targets that address causal human biology, predictive lab assays and clinical biomarkers, rapid paths to

registration and approval, and product candidates that hold the potential for transformative patient benefit. Our approach

includes advancing multiple compounds or therapies from each program into early clinical trials to obtain patient data that

can inform selection of the most promising therapies for later stage development as well as inform our ongoing discovery and

development efforts. We aim to serially innovate in our disease areas of interest and follow our first-in-class therapies with

potential best-in-class candidates. We plan to continue investing to advance our strategy, fostering scientific innovation by

identifying additional product candidates through internal research efforts, and investing in business development

transactions to access emerging technologies, products and product candidates.

Our serial innovation approach is intended to increase the likelihood of successfully bringing transformative medicines to

patients and to provide durable clinical and commercial success. We are working to ensure broad access for eligible patients

with these conditions in all countries with regulatory approval. Within our clinical pipeline, we are rapidly progressing

multiple programs into pivotal development. We maintain a strong financial profile as we continue to invest in our serial

innovation strategy, launch new products, advance our diverse pipeline, and expand geographically.

MARKETED PRODUCTS

Information regarding our marketed products, including information regarding the disease area, initial approval and age

group for which the therapy is approved, are set forth in the table below.

Disease		Initial Approval	Eligible Age Group**(1)**
Cystic Fibrosis
		2024	6 years of age and older
		2019	2 years of age and older
		2018	6 years of age and older
		2015	1 year of age and older
		2012	1 month of age and older
Sickle Cell Disease and Transfusion-Dependent Beta Thalassemia
		2023	12 years of age and older
Acute Pain
		2025	Adults

(1) Specifies the youngest eligible age group in any major market.

CF

CF is a life-shortening genetic disease caused by a defective or missing cystic fibrosis transmembrane conductance

receptor (“CFTR”) protein resulting from mutations in the CFTR gene. The absence of working CFTR protein results in poor

flow of salt and water into and out of cells in a number of organs, including the lungs, where mucus builds up, causing

chronic lung infections and progressive lung damage. Our CFTR modulators, including ivacaftor, deutivacaftor, lumacaftor,

tezacaftor, elexacaftor, and vanzacaftor, target the underlying cause of disease by improving CFTR protein function, and as

such have been shown to provide transformative benefit for people living with CF.

Our marketed CF medicines, ALYFTREK (

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Investing in our common stock involves a high degree of risk, and you should carefully consider the risks and

uncertainties described below in addition to the other information included or incorporated by reference in this Annual

Report on Form 10-K. If any of the following risks or uncertainties occur, our business, financial condition or results of

operations would likely suffer, possibly materially. In that case, the trading price of our common stock could decline.

Risks Related to Our Business and Products

Our success depends on our ability to develop and commercialize additional medicines.

We invest significant resources in research and development to discover and develop transformative medicines for

people with serious diseases. Product development is highly uncertain and expensive. Product candidates may appear

promising in research and development but may fail to reach commercial success for many reasons, including:

• the failure to establish safety and efficacy through clinical trials;

• the failure to obtain marketing approval;

• the inability to manufacture on economically feasible terms;

• the failure to gain and maintain market acceptance among physicians and patients or other members of the medical

community;

• the failure to obtain adequate pricing or reimbursement levels from third-party payors or foreign governments; and

• competition based on, among other factors, safety, efficacy, patient convenience, pricing and reimbursement.

If we are not able to successfully develop and commercialize additional medicines, our business would be materially

harmed.

Our business is substantially dependent on the success of our CF medicines.

Substantially all our net product revenues have been derived from the sale of our CF medicines. We may be unable to

sustain or increase revenues from sales of our CF medicines in the future for any number of reasons, including the potential

introduction of competitive products or the inability to successfully develop and commercialize next-generation medications

or medicines to treat people with CF who cannot benefit from our current CF medicines. Our concentrated source of revenue

increases the risks associated with potential manufacturing or supply disruptions, safety issues that may be identified with

respect to our CF medicines, and failure to gain and/or maintain market acceptance or adequate pricing or reimbursement for

our CF medicines. If we are unable to sustain or increase revenues from sales of our CF medicines, or if we do not meet the

expectations of investors, our business would be materially harmed and our ability to fund our operations could be adversely

affected.

If we are unable to successfully develop and commercialize medicines for acute and neuropathic pain, our business could

be materially harmed.

A portion of the value attributed to our company by investors is based on the expected commercial success of

JOURNAVX for acute pain and on our development programs for both acute and peripheral neuropathic pain. JOURNAVX

may not gain or maintain market acceptance among physicians, patients, or payors due to various factors, including the

availability of lower-cost alternatives, and sales, marketing, pricing, and/or distribution challenges associated with

introducing a product into a highly competitive market. Furthermore, we may not succeed in developing JOURNAVX for

additional indications or in advancing other product candidates, including NaV1.8 or NaV1.7 inhibitors, for the treatment of

acute or peripheral neuropathic pain. Even if we obtain marketing approvals for these product candidates, they will face

significant competition and there can be no assurance of commercial success.

We may not be able to increase or maintain CASGEVY product revenues.

The future commercial success of CASGEVY depends on physicians, patients, or payors accepting it as medically

useful, cost-effective, ethical, safe, and preferred with respect to current and potential future competitive therapies, and on

payors providing adequate reimbursement. In addition to risks generally associated with the commercialization of medicines,

the cell collection processes, manufacturing and other procedures required to manufacture and administer CASGEVY are

more complex, resource-intensive, and operationally demanding than for small molecules. For example, the cost of

manufacturing CASGEVY as a percentage of revenue is significantly higher than for our CF medicines. Moreover, market

acceptance continues to be dependent in part on the prevalence and severity of side effects associated with the procedure by

which CASGEVY is administered, including those resulting from the myeloablative preconditioning regime. There can be no

assurance that we will be able to increase or maintain our revenues from CASGEVY in future periods.

Risks Related to Commercialization

We are subject to pricing and reimbursement pressures that could have a material adverse effect on our business,

revenues, and results of operations.

Revenues from our products depend, to a large degree, on the extent to which the products are purchased by customers,

such as wholesalers, pharmacies, and hospitals, and reimbursed by third-party payors, such as government health programs,

commercial insurers, and managed health care organizations. Increasingly, these third-party payors are becoming more

critical in evaluating and reimbursing medicines. The containment of health care costs continues to be a priority for many

governments, and drug pricing has been a focus in this effort. The U.S. federal government and state legislatures and foreign

governments have shown significant and evolving interest in implementing cost-containment programs, including price

controls, restrictions on reimbursement, value-based and reference pricing, compulsory licensing, including the pursuit of so-

called “march in” rights, and mandatory substitution with generic products, all of which could limit the prices of, or access to,

our products. Decisions by third-party payors to not cover a product or restrict access to a product may shift over time and

could reduce market acceptance of the product and limit product revenues. We must also compete to be placed on formularies

of managed care providers, as exclusion of our products from a formulary would limit usage by managed care providers and

patients.

In the U.S., pricing and access is primarily governed by practices of private managed care providers and institutional and

governmental purchasers, federal laws and regulations related to Medicare and Medicaid, including the ACA and the IRA,

and state activities, including the establishment of PDABs and price transparency rules. For example, in August 2023, the

Colorado PDAB selected five drugs for an affordability review, including TRIKAFTA. Although the Colorado PDAB later

found TRIKAFTA to be ineligible for an upper payment limit we cannot predict whether future reviews by the Colorado

PDAB, or any other PDAB, will come to the same conclusion about TRIKAFTA or any of our other therapies, or the amount

of any potential upper payment limit. Furthermore, changes to the health care system enacted as part of health care reform in

the U.S., as well as increased purchasing power of entities that negotiate on behalf of Medicare, Medicaid, and private

payors, could result in further pricing pressures. For example, initiatives by the U.S. government to impose most-favored-

nation pricing on U.S. prescription drug prices in government programs, including the recently proposed GUARD Model by

the CMS. While there is significant uncertainty around the related executive orders and rulemaking, mandatory initiatives

could result in reduced pricing and reimbursement for our products.

In most markets outside of the U.S., the pricing and reimbursement medicines is subject to governmental control and

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We did not receive any written comments from the Securities and Exchange Commission prior to the date 180 days

before the end of the fiscal year ended December 31, 2025 regarding our filings under the Securities Exchange Act of 1934,

as amended, that have not been resolved.

Risk Management and Strategy

We recognize the critical importance of developing, implementing, and maintaining robust cybersecurity measures to

maintain the security, confidentiality, integrity, and availability of our business systems and confidential information,

including personal information and intellectual property. Our cybersecurity program includes systems and processes for

assessing, identifying and managing material risks from cybersecurity threats and include maintenance and monitoring of

information security policies aligned with global regulatory controls and aligned with National Institute of Standards and

Technology Cybersecurity Framework and System and Organization Controls 2. The program includes user and employee

awareness of cyber policies and practices; information systems configuration management; third-party risk management

systems; identity and information asset protection; infrastructure security systems; and cyber threat operations with

continuous monitoring and threat hunting. This program also includes processes to oversee and identify material risks from

cybersecurity threats associated with our use of third-party service providers. We engage a range of third-party experts in

connection with various development, implementation, and maintenance activities related to our cybersecurity program,

including audit and compliance, threat hunting, monitoring, and end-user support.

Our cybersecurity program is integrated into our overall risk management systems, including our annual enterprise risk

management program, internal audit program, business continuity and crisis management programs, third-party risk

management program, insurance risk management program, and employee compliance programs. As part of our overall risk

management program, we maintain a global insurance portfolio with comprehensive cyber coverage. Our Chief Information

Security Officer (“CISO”) and the Information Security function advises, consults with, or provides input to each of these

programs to ensure that material risks from cybersecurity threats are appropriately assessed, identified, and managed.

As of the date of this report, there have been no cybersecurity threats that have materially affected or are reasonably

likely to materially affect our business, operations, or financial condition. Similar to other companies, we have experienced

cybersecurity incidents, including temporary service interruptions of third-party suppliers. As of the date of this report,

however, known cybersecurity incidents, individually or in aggregate, have not had a material impact on our company. Over

the last three years, net expenses incurred from any information security breaches, including any penalties and settlements,

are not material relative to our total revenue. For additional discussion on cybersecurity risks we face, see Item 1.A, Risk

Factors – “A breakdown or breach of our information technology systems, or unauthorized access to confidential

information could adversely affect our business.” of this Annual Report on Form 10-K

Governance

While our board of directors has oversight responsibility for risk management generally, the Audit and Finance

Committee (“Audit Committee”) is specifically responsible for overseeing our cybersecurity risk management program to

ensure that cybersecurity risks are identified, assessed, managed, and monitored. Our CISO provides quarterly updates to the

Audit Committee in this regard, and covers the state of our cybersecurity program, supported by key performance indicators

across the range of cybersecurity functions related to risk management and governance, identity and information asset

protection, core security and endpoint security, and cyber threat operations. These updates include descriptions of

cybersecurity incidents of interest, including those associated with our third-party service providers; the board will be

informed promptly of material risks from cybersecurity threats.

We strive to create a culture of cybersecurity resilience and awareness and believe that cybersecurity is the responsibility

of every employee and contractor. At the same time, primary responsibility for assessing, monitoring, and managing our

cybersecurity risks lies with our CISO. Our CISO has more than 35 years of experience in security and information systems

and spent 25 years with Raytheon Technologies, most recently as Chief Technology Officer of Cybersecurity, Special

Missions, Training & Services. Our CISO supported the U.S. President's National Security Telecommunications Advisory

Committee for more than 20 years, is a member of the Massachusetts Cybersecurity Strategy Council, and previously served

as Chair of the Kogod Cybersecurity Governance Center at American University. He also served on the Rhode Island

Homeland Security Advisory Board and was a member of various commercial cyber product councils.

Our CISO oversees a team of skilled cybersecurity professionals who have Certified Information Systems Security

Professional credentials, Global Information Assurance Certification from the SANS Institute, and other security and network

certifications. The cybersecurity team monitors and evaluates our cybersecurity posture and performance on an ongoing

basis, including through regular vulnerability scans, penetration tests, and threat intelligence feeds. The cybersecurity team

uses various tools and methodologies to manage cybersecurity risk that are tested on a regular cadence, and assesses and

evaluates cybersecurity incidents, escalating certain cybersecurity incidents to the CISO according to protocol. The CISO is

continually informed regarding the performance of the cybersecurity program, as well as the latest developments in

cybersecurity, including potential threats and innovative risk management techniques aligned with industry standards. The

CISO reports to our Chief Digital and Information Officer, who is a Senior Vice President of the Company and reports

directly to our Chief Operating and Financial Officer (“COFO”). Our COFO is an Executive Vice President and an executive

officer of the Company, and reports directly to our CEO.

Corporate Headquarters

We lease approximately 1.1 million square feet of office and laboratory space at our corporate headquarters in Boston,

Massachusetts in two buildings pursuant to two leases that we entered into in May 2011 and amended in August 2024 to,

among other terms, extend the lease termination dates from December 2028 to June 2044. We have the option to extend the

term of the leases for up to two additional ten-year periods.

Additional United States and Worldwide Locations

In addition to our corporate headquarters, we lease an aggregate of approximately 865,000 square feet of space globally.

This space includes logistical, laboratory, commercial and manufacturing operations, as well as laboratory and office space to

support our research and development organizations. We also own approximately 213,000 square feet at our continuous

manufacturing facility in Massachusetts. Additionally, we are constructing the second building of our Leiden Campus in

Massachusetts (“Leiden II”), which will include approximately 348,000 square feet of office and laboratory space. We expect

Leiden II to be operational in late 2026.

Other than as described in Note P, “Commitments and Contingencies,” to our consolidated financial statements, we are

not currently subject to any material legal proceedings.

Not applicable.

PART II

ISSUER PURCHASES OF EQUITY SECURITIES

Market Information

Our common stock is traded on The Nasdaq Global Select Market under the symbol “VRTX.”

Shareholders

As of February 6, 2026, there were 94 holders of record of our common stock.

Performance Graph

Our performance graph includes the NASDAQ Biotechnology Index, which we believe is a comparable index consisting

of companies with similar industry classifications, and which we plan to use in our future performance graphs.

Dividends

We have never paid any cash dividends on our common stock, and we do not anticipate paying any in the foreseeable

future.

Issuer Repurchases of Equity Securities

In May 2025, our Board of Directors approved a share repurchase program (our “2025 Share Repurchase Program”),

pursuant to which we are authorized to repurchase up to $4.0 billion of our common stock. The 2025 Share Repurchase

Program does not have an expiration date and can be discontinued at any time.

The table set forth below shows repurchases of securities by us during the three months ended December 31, 2025 under

our 2025 Share Repurchase Program.

(1)Under our 2025 Share Repurchase Program, we are authorized to purchase shares from time to time through open market or privately

negotiated transactions. Such purchases may be made pursuant to Rule 10b5-1 plans or other means as determined by our management

and in accordance with the requirements of the Securities and Exchange Commission.

OPERATIONS

Our discussion and analysis of our financial condition and results of operations for 2025 as compared to 2024 are

discussed below. For a discussion of our financial condition and results of operations for 2024 as compared to 2023*, please*

refer to Item 7, “Management’s Discussion and Analysis of Financial Condition and Results of Operations” in our 2024

Annual Report on Form 10-K, except as set forth below.

OVERVIEW

We are a global biotechnology company that invests in scientific innovation to create transformative medicines for

people with serious diseases, with a focus on specialty markets. We have approved medicines for cystic fibrosis (“CF”),

sickle cell disease (“SCD”), transfusion dependent beta thalassemia (“TDT”), and acute pain, and we continue to serially

innovate and advance next-generation clinical and research programs in these areas. Our mid- and late-stage clinical pipeline

includes programs across a range of modalities in additional serious diseases, including IgA nephropathy, APOL1-mediated

kidney disease, neuropathic pain, type 1 diabetes, primary membranous nephropathy, autosomal dominant polycystic kidney

disease, and myotonic dystrophy type 1.

Collectively, our five CF medicines, led by TRIKAFTA/KAFTRIO, are being used to treat nearly three quarters of the

people with CF in the U.S., Europe, Australia, and Canada. ALYFTREK, our newest CF medicine, is approved in the United

States (the “U.S.”), the United Kingdom (the “U.K.”), the European Union (the “E.U.”), Canada, New Zealand, Switzerland,

Australia and Israel.

CASGEVY, our ex-vivo, non-viral CRISPR/Cas9 gene-edited cell therapy, is approved in the U.S., the E.U., the U.K.,

the Kingdom of Saudi Arabia (“Saudi Arabia”), the Kingdom of Bahrain (“Bahrain”), Qatar, the United Arab Emirates (the

“UAE”), Kuwait, Switzerland and Canada for the treatment of people 12 years of age and older with SCD or TDT.

JOURNAVX, our selective non-opioid NaV1.8 pain signal inhibitor, is approved in the U.S. for the treatment of people

with moderate-to-severe acute pain. We are continuing our commercial launch of JOURNAVX for eligible adults.

Financial Highlights

$0.1

$0.1

2024

2025

December 31, 2025

December 31, 2024

Note: Charts above may not add due to rounding.

Business Updates

Marketed Products

Cystic Fibrosis

We expect that the number of people with CF taking our medicines will continue to grow through new approvals and

reimbursement agreements, treatment of younger patients, increased survival and expansion into additional geographies.

• ALYFTREK is reimbursed for eligible people with CF in the U.S., England, Ireland, Germany, Denmark, Northern

Ireland, Norway, Wales, Italy, Australia, New Zealand and Luxembourg. We are working to secure access for

eligible patients in additional countries.

Sickle Cell Disease and Beta Thalassemia

• In 2025, we recorded $115.8 million of CASGEVY product revenues. This reflects 64 patients receiving infusions

of CASGEVY in 2025, including 30 people infused in the fourth quarter. Globally, in 2025, 147 people with SCD or

TDT had their first cell collection for CASGEVY.

• As of the end of 2025, approximately 90 percent of people with SCD or TDT in the U.S. have reimbursed access to

CASGEVY, which is also reimbursed in the U.K., Italy, Austria, Denmark, Luxembourg, Saudi Arabia, the UAE,

Bahrain, and Kuwait. In January 2026, we secured reimbursed access to CASGEVY for eligible people with SCD in

Scotland, consistent with the reimbursement agreement reached in 2025 for people with TDT.

• We expect to begin global regulatory submissions for approvals for CASGEVY in children 5 to 11 years of age, in

the first half of 2026. The FDA awarded Vertex with a Commissioner’s National Priority Voucher for this pediatric

submission, indicating an accelerated timeline for review once the submission is complete.

Acute Pain

• Since pharmacy availability in March 2025 through year-end 2025, more than 550,000 prescriptions for

JOURNAVX were written and filled across the hospital and retail settings in different acute pain conditions,

consistent with JOURNAVX’s broad label.

• We have secured access for JOURNAVX with all three national pharmacy benefit managers, and, as of January

2026, over 200 million individuals across commercial and government payers have coverage, representing two-

thirds of U.S. covered lives. In addition, 21 states provide coverage via Medicaid.

• More than 100 of the targeted 150 healthcare systems and more than 950 individual hospitals of the 2,000 targeted

institutions have added JOURNAVX to formularies, protocols or order sets.

Select R&D Pipeline Programs

We continue to advance a diversified pipeline of potentially transformative medicines for serious diseases utilizing a

range of modalities. Recent and anticipated progress in activities supporting these efforts is included below:

Cystic Fibrosis

• We completed the global trial evaluating ALYFTREK in children 2 to 5 years of age. Following positive results

from this clinical trial, we expect to submit for approval with global regulators in this age group in the first half of

2026. We also initiated a pivotal trial of ALYFTREK in children 1 year to less than 2 years of age.

• Following positive results from the clinical trial evaluating TRIKAFTA in children 1 year to less than 2 years of age,

we expect to begin submissions for global regulatory approvals in this age group in the first half of 2026.

IgA Nephropathy

• We are developing povetacicept, a dual inhibitor of B cell activating factor (“BAFF”) and a proliferation-inducing

ligand (“APRIL”) cytokines, for multiple diseases. Povetacicept represents a potentially best-in-class approach to

control B cell activity in immunoglobulin A nephropathy (“IgAN”).

• We completed enrollment in the Phase 3 clinical trial evaluating povetacicept for IgAN and, in the fourth quarter of

2025, we initiated the rolling Biologics Licensing Application (“BLA”) filing for U.S. accelerated approval with

submission of the first module. We expect to release interim analy

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Interest Rate Risk

Financial Instruments

As part of our investment portfolio, we own financial instruments that are sensitive to market risks. The investment

portfolio is used to preserve our capital, provide adequate liquidity and earn returns commensurate with our risk appetite. We

invest in instruments that meet the credit quality standards outlined in our investment policy, which also limits the amount of

credit exposure to any one issue or type of instrument. These instruments primarily include securities issued by the U.S.

government and its agencies, investment-grade corporate bonds, asset-backed securities and money market funds. These

investments are primarily denominated in U.S. Dollars and none are held for trading purposes.

All of our interest-bearing securities are subject to interest rate risk and could change in value if interest rates fluctuate.

Substantially all of our investment portfolio consists of marketable securities with active secondary or resale markets to help

ensure portfolio liquidity, and we have implemented guidelines limiting the term-to-maturity of our investment instruments.

Since we account for these securities as available-for-sale, no gains or losses are realized due to changes in the fair value of

our investments unless we sell our investments prior to maturity or incur a credit loss. Due to the conservative nature of these

instruments, we do not believe that the fair value of our investments has a material exposure to interest rate risk.

While we are exposed to global interest rate fluctuations, our investment portfolio is most affected by fluctuations in U.S.

interest rates, which affect the interest earned on our cash, cash equivalents and marketable securities.

Credit Agreement

In 2022, we entered into a $500.0 million unsecured revolving credit facility (“credit agreement”). Loans under this

credit agreement bear interest, at our option, at a base rate or a Secured Overnight Financing Rate (“SOFR”), plus an

applicable margin based on our consolidated leverage ratio (the ratio of our total consolidated funded indebtedness to our

consolidated EBITDA for the most recently completed four fiscal quarter period). Pursuant to our credit agreement, the

applicable margin on base rate loans ranges from 0.000% to 0.500% and the applicable margin on SOFR loans ranges from

1.000% to 1.500%. We do not believe that changes in interest rates related to our credit agreement would have a material

effect on our consolidated financial statements. As of December 31, 2025, we had no principal or interest outstanding under

our credit facility. A portion of our “Interest expense” in 2026 will be dependent on whether, and to what extent, we borrow

amounts under this facility.

Foreign Exchange Market Risk

As a result of our foreign operations, we face significant exposure to movements in foreign currency exchange rates

between the U.S. dollar and various foreign currencies, the most significant of which is the Euro. Fluctuations in the amounts

of our foreign revenues and fluctuations in foreign currency exchange rates, may have a positive or negative effect on our

foreign exchange rate exposure. The current exposures arise primarily from cash, accounts receivable, intercompany

receivables and payables, payables, and accruals, and inventories.

We have a foreign currency management program, which is separate from our investment policy and portfolio, with the

objective of reducing the effect of exchange rate fluctuations on our operating results and forecasted revenues denominated in

foreign currencies. We have cash flow hedges related to a portion of our forecasted product revenues that qualify for hedge

accounting treatment under U.S. GAAP. We do not seek hedge accounting treatment for our foreign currency forward

contracts related to monetary assets and liabilities that impact our operating results. As of December 31, 2025, we held

foreign exchange forward contracts that were designated as cash flow hedges with notional amounts totaling $6.1 billion

representing a net liability of $111.5 million on our consolidated balance sheet.

Although not predictive in nature, we believe a hypothetical 10% threshold reflects a reasonably possible near-term

change in exchange rates. If the December 31, 2025 exchange rates were to change by a hypothetical 10%, the fair value

recorded on our consolidated balance sheet related to our foreign exchange forward contracts that were designated as cash

flow hedges as of December 31, 2025 would change by approximately $608.0 million. However, since these contracts hedge

a specific portion of our forecasted product revenues denominated in certain foreign currencies, any change in the fair value

of these contracts is recorded in “Accumulated other comprehensive (loss) income” on our consolidated balance sheets and is

reclassified to earnings in the same periods during which the underlying product revenues affect earnings. Therefore, any

change in the fair value of these contracts that would result from a hypothetical 10% change in exchange rates would be

entirely offset by the change in value associated with the underlying hedged product revenues resulting in no impact on our

future anticipated earnings and cash flows with respect to the hedged portion of our forecasted product revenues.

The information required by this Item 8 is contained on pages F-1 through F-49 of this Annual Report on Form 10-K.

FINANCIAL DISCLOSURE

Not applicable.

(1) Evaluation of Disclosure Controls and Procedures. Our chief executive officer and chief financial officer, after

evaluating the effectiveness of our disclosure controls and procedures (as defined in Rule 13a-15(e) and Rule 15d-15(e)

promulgated under the Securities Exchange Act of 1934, as amended (the “Exchange Act”)) as of the end of the period

covered by this Annual Report on Form 10-K, have concluded that, based on such evaluation, our disclosure controls and

procedures were effective. In designing and evaluating the disclosure controls and procedures, management recognized that

any controls and procedures, no matter how well designed and operated, can provide only reasonable assurance of achieving

the desired control objectives, and management necessarily was required to apply our judgment in evaluating the cost-benefit

relationship of possible controls and procedures.

(2) Management’s Annual Report on Internal Control Over Financial Reporting. Management is responsible for

establishing and maintaining adequate internal control over financial reporting. Internal control over financial reporting is

defined in Rule 13a-15(f) and Rule 15d-15(f) promulgated under the Exchange Act, as a process designed by, or under the

supervision of, our principal executive and principal financial officers and effected by our board of directors, management

and other personnel, to provide reasonable assurance regarding the reliability of financial reporting and the preparation of

financial statements for external purposes in accordance with generally accepted accounting principles. Our internal control

over financial reporting include those policies and procedures that:

• pertain to the maintenance of records that, in reasonable detail, accurately and fairly reflect the transactions and

dispositions of our assets;

• provide reasonable assurance that transactions are recorded as necessary to permit preparation of financial

statements in accordance with generally accepted accounting principles, and that our receipts and expenditures are

being made only in accordance with authorizations of management and our directors; and

• provide reasonable assurance regarding prevention or timely detection of unauthorized acquisition, use or

disposition of our assets that could have a material effect on the financial statements.

Because of its inherent limitations, internal control over financial reporting may not prevent or detect misstatements.

Also, projections of any evaluation of effectiveness to future periods are subject to the risk that controls may become

inadequate because of changes in conditions, or that the degree of compliance with the policies or procedures may

deteriorate.

Management assessed the effectiveness of our internal control over financial reporting as of December 31, 2025. In

making this assessment, we used the criteria set forth in the Internal Control—Integrated Framework (2013) issued by the

Committee of Sponsoring Organizations of the Treadway Commission (“COSO”). Based on our assessment, management has

concluded that, as of December 31, 2025, our internal control over financial reporting is effective based on those criteria.

Our independent registered public accounting firm, Ernst & Young LLP, issued an attestation report on our internal

control over financial reporting. See Section 4 below.

(3) Changes in Internal Controls. During the quarter ended December 31, 2025, there were no changes in our internal

control over financial reporting that materially affected, or are reasonably likely to materially affect, our internal control over

financial reporting.

(4) Report of Independent Registered Public Accounting Firm

To the Shareholders and the Board of Directors of Vertex Pharmaceuticals Incorporated

Opinion on Internal Control Over Financial Reporting

We have audited Vertex Pharmaceuticals Incorporated’s internal control over financial reporting as of December 31, 2025,

based on criteria established in Internal Control*—*Integrated Framework issued by the Committee of Sponsoring

Organizations of the Treadway Commission (2013 framework) (the COSO criteria). In our opinion, Vertex Pharmaceuticals

Incorporated (the Company) maintained, in all material respects, effective internal control over financial reporting as of

December 31, 2025, based on the COSO criteria.

We also have audited, in accordance with the standards of the Public Company Accounting Oversight Board (United States)

(PCAOB), the 2025 consolidated financial statements of the Company and our report dated February 13, 2026 expressed an

unqualified opinion thereon.

Basis for Opinion

The Company’s management is responsible for maintaining effective internal control over financial reporting and for its

assessment of the effectiveness of internal control over financial reporting included in the accompanying Management’s

Annual Report on Internal Control Over Financial Reporting. Our responsibility is to express an opinion on the Company’s

internal control over financial reporting based on our audit. We are a public accounting firm registered with the PCAOB and

are required to be independent with respect to the Company in accordance with the U.S. federal securities laws and the

applicable rules and regulations of the Securities and Exchange Commission and the PCAOB.

We conducted our audit in accordance with the standards of the PCAOB. Those standards require that we plan and perform

the audit to obtain reasonable assurance about whether effective internal control over financial reporting was maintained in

all material respects.

Our audit included obtaining an understanding of internal control over financial reporting, assessing the risk that a material

weakness exists, testing and evaluating the design and operating effectiveness of internal control based on the assessed risk,

and performing such other procedures as we considered necessary in the circumstances. We believe that our audit provides a

reasonable basis for our opinion.

Definition and Limitations of Internal Control Over Financial Reporting

A company’s internal control over financial reporting is a process designed to provide reasonable assurance regarding the

reliability of financial reporting and the preparation of financial statements for external purposes in accordance with generally

accepted accounting principles. A company’s internal control over financial reporting includes those policies and procedures

that (1) pertain to the maintenance of records that, in reasonable detail, accurately and fairly reflect the transactions and

dispositions of the assets of the company; (2) provide reasonable assurance that transactions are recorded as necessary to

permit preparation of financial statements in accordance with generally accepted accounting principles, and that receipts and

expenditures of the company are being made only in accordance with authorizations of management and directors of the

company; and (3) provide reasonable assurance regarding prevention or timely detection of unauthorized acquisition, use, or

disposition of the company’s assets that could have a material effect on the financial statements.

Because of its inherent limitations, internal control over financial reporting may not prevent or detect misstatements. Also,

projections of any evaluation of effectiveness to future periods are subject to the risk that controls may become inadequate

because of changes in conditions, or that the degree of compliance with the policies or procedures may deteriorate.

/s/ Ernst & Young LLP

Boston, Massachusetts

February 13, 2026

Rule 10b5-1 Trading Plans

Our policy governing transactions in our securities by our directors, officers, and employees permits our officers,

directors and employees to enter into trading plans complying with Rule 10b5-1 under the Exchange Act. The following table

describes the written plans for the sale of our securities adopted by our directors and officers (as defined in Rule 16a-1(f)

under the Exchange Act) during the fourth quarter of 2025, each of which is intended to satisfy the affirmative defense

conditions of Rule 10b5-1 (each, a “Trading Plan”). Other than as described in the table below, none of our directors or

officers adopted, modified or terminated a Trading Plan in the fourth quarter of 2025.

2026 Restated Articles of Organizatio**n

On February 12, 2026, the Company filed Restated Articles of Organization with the Secretary of the Commonwealth of

Massachusetts to consolidate its Articles of Organization and all prior amendments and to remove references to the Series A

Junior Participating Preferred Stock, which is no longer outstanding. The restatement was effected for clarity only and did not

result in any changes to the rights of holders of the Company’s common stock.

A copy of the Restated Articles of Organization is filed as Exhibit 3.1 to this Annual Report on Form 10-K and is

incorporated herein by reference.

None.

PART III

Portions of our definitive Proxy Statement for the 2026 Annual Meeting of Shareholders (“2026 Proxy Statement”) are

incorporated by reference into this Part III of our Annual Report on Form 10-K.

The information regarding directors required by this Item 10 will be included in our 2026 Proxy Statement and is

incorporated herein by reference. We expect this information to be provided under “Election of Directors,” “Corporate

Governance and Risk Management,” “Shareholder Proposals for the 2027 Annual Meeting and Nominations for Director,”

“Delinquent Section 16(a) Reports” and “Code of Conduct.” The information regarding executive officers required by this

Item 10 is included in Part I of this Annual Report on Form 10-K.

We have adopted insider trading policies and procedures governing the purchase, sale and/or other dispositions of our

securities by directors, officers and employees, or Vertex itself, that are reasonably designed to promote compliance with

insider trading laws, rules and regulations and any listing standards applicable to us. A copy of our Insider Trading Policy is

filed as Exhibit 19.1 to this Annual Report on Form 10-K.

The information required by this Item 11 will be included in the 2026 Proxy Statement and is incorporated herein by

reference. We expect this information to be provided under “Compensation Committee Interlocks and Insider Participation,”

“Compensation Discussion and Analysis,” “Compensation and Equity Tables,” “Director Compensation,” “Management

Development and Compensation Committee Report” and/or “Corporate Governance and Risk Management.”

RELATED STOCKHOLDER MATTERS

The information required by this Item 12 will be included in the 2026 Proxy Statement and is incorporated herein by

reference. We expect this information to be provided under “Security Ownership of Certain Beneficial Owners and

Management” and “Equity Compensation Plan Information.”

The information required by this Item 13 will be included in the 2026 Proxy Statement and is incorporated herein by

reference. We expect this information to be provided under “Election of Directors,” “Corporate Governance and Risk

Management,” and “Audit and Finance Committee.”

The information required by this Item 14 will be included in the 2026 Proxy Statement and is incorporated herein by

reference. We expect this information to be provided under “Ratification of the Appointment of Independent Registered

Public Accounting Firm.”

PART IV

(a)(1) The Financial Statements required to be filed by Items 8 and 15(c) of Form 10-K, and filed herewith, are as

follows:

(a)(2) Financial Statement Schedules have been omitted because they are either not applicable or the required

information is included in the consolidated financial statements or notes thereto listed in (a)(1) above.

(a)(3) Exhibits.

The following is a list of exhibits filed as part of this Annual Report on Form 10-K.

Not applicable.

SIGNATURES

Pursuant to the requirements of Section 13 or 15(d) of the Securities Exchange Act of 1934, the registrant has duly

caused this report to be signed on its behalf by the undersigned, thereunto duly authorized.

Pursuant to the requirements of the Securities Exchange Act of 1934, this report has been signed below by the following

persons on behalf of the registrant and in the capacities and on the dates indicated.

F-1

Report of Independent Registered Public Accounting Firm

To the Shareholders and the Board of Directors of Vertex Pharmaceuticals Incorporated

Opinion on the Financial Statements

We have audited the accompanying consolidated balance sheets of Vertex Pharmaceuticals Incorporated (the Company) as of

December 31, 2025 and 2024, the related consolidated statements of income (loss), comprehensive income (loss),

shareholders’ equity and cash flows for each of the three years in the period ended December 31, 2025, and the related notes

(collectively referred to as the “consolidated financial statements”). In our opinion, the consolidated financial statements

present fairly, in all material respects, the financial position of the Company at December 31, 2025 and 2024, and the results

of its operations and its cash flows for each of the three years in the period ended December 31, 2025, in conformity with

U.S. generally accepted accounting principles.

We also have audited, in accordance with the standards of the Public Company Accounting Oversight Board (United States)

(PCAOB), the Company’s internal control over financial reporting as of December 31, 2025, based on criteria established in

Internal Control*—*Integrated Framework issued by the Committee of Sponsoring Organizations of the Treadway Commission

(2013 framework), and our report dated February 13, 2026 expressed an unqualified opinion thereon.

Basis for Opinion

These financial statements are the responsibility of the Company’s management. Our responsibility is to express an opinion

on the Company’s financial statements based on our audits. We are a public accounting firm registered with the PCAOB and

are required to be independent with respect to the Company in accordance with the U.S. federal securities laws and the

applicable rules and regulations of the Securities and Exchange Commission and the PCAOB.

We conducted our audits in accordance with the standards of the PCAOB. Those standards require that we plan and perform

the audit to obtain reasonable assurance about whether the financial statements are free of material misstatement, whether due

to error or fraud. Our audits included performing procedures to assess the risks of material misstatement of the financial

statements, whether due to error or fraud, and performing procedures that respond to those risks. Such procedures included

examining, on a test basis, evidence regarding the amounts and disclosures in the financial statements. Our audits also

included evaluating the accounting principles used and significant estimates made by management, as well as evaluating the

overall presentation of the financial statements. We believe that our audits provide a reasonable basis for our opinion.

Critical Audit Matter

The critical audit matter communicated below is a matter arising from the current period audit of the financial statements that

was communicated or required to be communicated to the audit committee and that: (1) relates to accounts or disclosures that

are material to the financial statements and (2) involved our especially challenging, subjective or complex judgments. The

communication of the critical audit matter does not alter in any way our opinion on the consolidated financial statements,

taken as a whole, and we are not, by communicating the critical audit matter below, providing a separate opinion on the

critical audit matter or on the accounts or disclosures to which it relates.

F-2

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