vrtx-20251231
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:
Title of Each Class Trading Symbol Name of Each Exchange on Which Registered
Common Stock, $0.01 Par Value Per Share VRTX The Nasdaq Global Select Market
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
PART I
Item 1. Business 1
Information about our Executive Officers 22
Item 1A. Risk Factors 24
Item 1B. Unresolved Staff Comments 39
Item 1C. Cybersecurity 39
Item 2. Properties 40
Item 3. Legal Proceedings 41
Item 4. Mine Safety Disclosures 41
PART II
Item 6. [Reserved] 43
Item 7A. Quantitative and Qualitative Disclosures About Market Risk 60
Item 8. Financial Statements and Supplementary Data 61
Item 9A. Controls and Procedures 61
Item 9B. Other Information 64
Item 9C. Disclosure Regarding Foreign Jurisdictions that Prevent Inspections 64
PART III
Item 10. Directors, Executive Officers and Corporate Governance 65
Item 11. Executive Compensation 65
Item 14. Principal Accountant Fees and Services 65
PART IV
Item 15. Exhibits and Financial Statement Schedules 66
Signatures 70
“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.
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PART I
ITEM 1.BUSINESS
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.
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•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.
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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
Acute Pain
(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 (vanzacaftor/tezacaftor/deutivacaftor), TRIKAFTA/KAFTRIO (elexacaftor/
tezacaftor/ivacaftor and ivacaftor), SYMDEKO/SYMKEVI (tezacaftor/ivacaftor and ivacaftor), ORKAMBI (lumacaftor/
ivacaftor) and KALYDECO (ivacaftor), are being used by nearly three quarters of the approximately 97,000 people with CF
in the U.S., Europe, Australia, and Canada. We estimate that there are approximately 112,000 people with CF in all target
markets.
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Our CF medicines are reimbursed or accessible in more than 60 countries across six continents. ALYFTREK, our most-
recently approved triple combination CF medicine, has the benefit of a once-daily dosing regimen and demonstrated non-
inferiority to TRIKAFTA in ppFEV1, a measure of lung function, and an improvement in sweat chloride levels as compared
to TRIKAFTA. We expect that the majority of people with CF will transition to ALYFTREK over time.
Sickle Cell Disease and Transfusion-Dependent Beta Thalassemia
SCD and TDT are hemoglobinopathies, a group of inherited blood disorders that result from gene mutations that alter
hemoglobin, a protein in red blood cells that delivers oxygen throughout the body.
SCD is caused by the change of a single amino acid in the β-hemoglobin gene that causes red cells to change shape in
settings of low oxygen. These sickled cells block blood flow and can lead to severe pain (known as vaso-occlusive crises),
organ damage, and shortened life span. Treatment is typically focused on relieving pain and minimizing organ damage,
requiring medication and, for some patients, monthly blood transfusions and frequent hospital visits.
Beta thalassemia is caused by loss-of-function mutations in the same β-hemoglobin gene that lead to severe anemia in
patients, which causes fatigue and shortness of breath. In infants, beta thalassemia causes failure to thrive, jaundice, and
feeding problems. Complications of beta thalassemia can lead to an enlarged spleen, liver and/or heart, misshapen bones and
delayed puberty. Treatment for beta thalassemia varies depending on the disease severity for each patient. People with TDT,
the most severe form of the disease, require regular blood transfusions, as frequently as every two to four weeks. Repeated
blood transfusions eventually cause an unhealthy buildup of iron in the patient, leading to organ damage.
CASGEVY (exagamglogene autotemcel), our ex-vivo, non-viral CRISPR/Cas9-based gene-editing therapy for severe
SCD and TDT, is approved in the U.S. and across multiple geographies including Europe, Canada, and the Middle East. We
estimate approximately 60,000 people with severe SCD or TDT are or could become eligible for CASGEVY in these
geographies. To receive CASGEVY, patients first undergo a treatment at an authorized treatment center (“ATC”) that
mobilizes a population of hematopoietic stem and progenitor cells (“HSPC”) from the bone marrow into the bloodstream.
These cells are collected from the patient’s bloodstream and transferred to a manufacturing facility where the HSPCs are
isolated and CRISPR/Cas9 gene-editing is performed on the cells. The gene-editing procedure results in a precise and specific
gene-edit in a non-coding intron of the BCL11A gene. Following manufacturing, the edited cells, now called CASGEVY, are
transferred back to the ATC. Patients are preconditioned with a myeloablative conditioning treatment that ablates their bone
marrow to create space for the edited cells. After CASGEVY is infused into the patient and the edited cells engraft, the levels
of fetal hemoglobin erythrocytes increase, thereby reducing or eliminating symptoms associated with disease. Efficacy data
support the profile of CASGEVY as a potential one-time functional cure for people with severe SCD and TDT.
CASGEVY is broadly reimbursed by third-party payors in the U.S., including the federal government and commercial
payors. In addition, we have agreements with national and regional payors covering more than 275 million lives, to provide
access to CASGEVY. Outside of the U.S., patients have access to CASGEVY in Austria, Denmark, the U.K., Italy,
Luxembourg, Bahrain, Saudi Arabia, the UAE, and Kuwait. We continue to expand access and pursue additional long-term
reimbursement arrangements and to engage with payors in the E.U. and the Middle East.
Globally in 2025, approximately 300 people with SCD or TDT initiated treatment with CASGEVY, 147 people had their
first cell collection for CASGEVY, and 64 people received infusions of CASGEVY. In 2026, we expect to reach more
eligible patients and drive patient infusions through our global ATC network.
Acute Pain
Acute pain is a disabling condition that may occur suddenly but typically lasts less than 90 days and resolves in days or
weeks (for example, following surgery or an injury). It is estimated that over 80 million people are prescribed a medicine for
acute pain every year in the U.S. Currently available treatments have limitations around efficacy or side effects, including a
risk of addiction with opioids. Because of these challenges, over- and under-utilization, as well as misutilization, of current
pain medicines may occur.
JOURNAVX (suzetrigine) is a first-in-class, oral pain signal inhibitor that is highly selective for voltage-gated sodium
channel NaV1.8. Through this mechanism, JOURNAVX provides effective relief of pain without evidence of the several
limitations of other currently available therapies, including the addictive potential of opioids. JOURNAVX was approved by
the U.S. Food and Drug Administration (“FDA”) in January 2025 for the treatment of moderate-to-severe acute pain in
adults.
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Since JOURNAVX became available at U.S. pharmacies in March 2025 and through the end of 2025, more than 550,000
prescriptions were written and filled across the hospital and retail settings in different acute pain conditions, consistent with
the product’s broad label. We have secured access for JOURNAVX with all three national pharmacy benefit managers, and
as of January 2026, more than 200 million individuals across commercial and government payors have coverage to
JOURNAVX, representing two-thirds of U.S. covered lives. In addition, 21 states provide coverage via Medicaid.
COMMERCIALIZATION OF OUR MEDICINES
We sell our medicines primarily to a limited number of specialty pharmacy and specialty distributors globally, as well as
to certain major wholesalers in the U.S. Our customers in the U.S. subsequently resell our medicines to patients, health care
providers, retail pharmacies, hospitals, or ATCs. Outside of the U.S., we generate sales primarily through distributor
arrangements and to retail pharmacies, as well as to hospitals and clinics, many of which are government-owned or supported
customers. In certain markets, we may not utilize a specialty distributor or specialty pharmacy to distribute CASGEVY and
instead may sell CASGEVY directly to ATCs. We contract with government agencies so that our medicines will be eligible
for purchase by, or partial or full reimbursement from, such third-party payors.
We promote the use of our medicines directly to healthcare professionals and organizations such as doctors, nurse
practitioners, physician assistants, pharmacists, hospitals, and pharmacy benefit managers. Through our field sales and
medical organizations, we explain the risks and benefits of our medicines to these healthcare professionals and organizations.
Our marketing is limited to the approved uses of the particular medicine. We also continue to develop scientific data and
other information about potential additional uses of our medicines and provide such information through clinical or medical
affairs teams as scientific exchange at scientific congresses or in other ways, including the development of publications, or in
response to unsolicited inquiries from healthcare professionals and organizations. In the U.S., we also market directly to
consumers by communicating the approved uses, benefits and risks.
We are dedicated to helping patients obtain access to our therapies. We work to gain access for our medicines on
formularies and reimbursement plans (lists of formulary-recommended or approved medicines and other products) by
providing information about the clinical profiles of our medicines. Our patient support representatives help patients
understand their insurance coverage and, in the U.S., we have established programs that provide co-pay assistance or free
medicine for qualified uninsured or underinsured patients, based on specific eligibility criteria.
RESEARCH AND DEVELOPMENT PROGRAMS
We invest in research and development to discover and develop transformative medicines for people with serious
diseases, with a focus on specialty markets. Our research strategy is to combine transformative advances in the understanding
of human disease and in the science of therapeutics to dramatically advance human health. We focus on:
•disease areas with known causal human biology;
•targets validated by causal human biology;
•predictive lab assays and clinical biomarkers;
•potential for transformative benefit regardless of modality; and
•efficient path to registration and approval.
Our development-stage product candidates are focused on the treatment of serious diseases. In pursuit of serial
innovation, our research and development approach includes advancing multiple candidates into clinical trials and pursuing
multiple modalities with the goal of bringing first-in-class and/or best-in-class therapies to patients.
Our research and development strategy has been validated through our success in moving novel product candidates into
clinical trials and obtaining marketing approvals for our five CF medicines, CASGEVY, and JOURNAVX. Our approach to
drug discovery has been further validated by ongoing pivotal development in five additional disease areas: in IgAN and pMN
with povetacicept, in AMKD with inaxaplin, in T1D with zimislecel, and in diabetic peripheral neuropathy with suzetrigine.
To augment our internal programs, we acquire businesses and technologies and collaborate with biopharmaceutical and
technology companies, leading academic research institutions, government laboratories, foundations and other organizations
to advance research in our disease areas of interest, as well as to access technologies needed to execute on our strategy. Our
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internal and external innovation approaches are based on the same strategy, which enables us to effectively integrate and
execute on new internal capabilities as we invest in external innovation. Our investments in external innovation include our
collaboration with CRISPR, which resulted in the successful development and approval of CASGEVY; our acquisition of
Semma Therapeutics, Inc. (“Semma”), which established and advanced our T1D program; our expansion of our renal
programs through our acquisition of Alpine Immune Sciences, Inc. (“Alpine”); our mRNA therapeutic, VX-522, for
treatment of CF through our collaboration with Moderna; and our intracellular therapeutic for myotonic dystrophy type 1
(“DM1”), VX-670, through our collaboration with Entrada.
CF
Our goal in CF is to continue to extend our leadership by developing treatment regimens that will provide benefits to all
people with CF. We have completed the Phase 3 clinical trial evaluating TRIKAFTA/KAFTRIO in children one year to less
than two years of age. The data showed that TRIKAFTA was generally safe and well-tolerated, consistent with the
established safety profile. Treatment with TRIKAFTA in this age group resulted in rapid, robust, and clinically meaningful
improvement in the secondary endpoint of sweat chloride reduction. We expect to begin submissions for global regulatory
approvals in this age group in the first half of 2026. We completed the global trial evaluating ALYFTREK in children 2 to 5
years of age. The data showed that ALYFTREK was generally safe and well-tolerated, consistent with the established safety
profile. Treatment with ALYFTREK in this age group resulted in a clinically meaningful improvement in the CFTR function
as measured by sweat chloride. We expect to submit for approval with global regulators in this age group in the first half of
2026. In addition, we initiated a pivotal trial evaluating ALYFTREK in children one to less than two years of age.
We estimate that nearly 95% of people with CF could benefit from our five approved medicines, and, in connection with
our serial innovation approach, we continue to identify and develop additional CFTR modulators with the goal of developing
best-in-class medicines that can treat more people with CF. We have advanced several next-generation, 3.0 CFTR modulators
into the clinic. VX-828 is the first of these and is being evaluated in a proof-of-concept clinical trial of people with CF. We
expect to complete enrollment and dosing in the first half of 2026. We are also enrolling and dosing in a Phase 1 clinical trial
of VX-581, another corrector in the next-generation 3.0 class, in healthy volunteers.
To treat people with CF who do not make full-length CFTR protein, and as a result, cannot benefit from our CFTR
modulators, we are researching and developing genetic therapies, such as mRNA, and gene-editing approaches to CF. In
collaboration with Moderna, we are developing VX-522, a nebulized CF mRNA therapeutic designed to treat the underlying
cause of CF lung disease for these people by enabling cells in the lungs to produce functional CFTR protein. We are targeting
completion of dosing in the multiple ascending dose portion of the Phase 1/2 clinical trial evaluating VX-522 and disclosure
of the data in the second half of 2026.
Sickle Cell Disease and Transfusion-Dependent Beta Thalassemia
In December 2025, we presented positive data from the pivotal trials evaluating CASGEVY in children 5 to 11 years of
age with severe SCD (the CLIMB SCD-151 clinical trial) and TDT (the CLIMB THAL-141 clinical trial). We expect to
initiate global regulatory submissions for this age group, including in the U.S., in the first half of 2026. In the U.S.,
CASGEVY has received a Commissioner’s National Priority Voucher for use in this age group, which is meant to accelerate
the FDA’s review of the application once submitted.
In connection with our serial innovation approach, we are advancing preclinical assets for myeloablative conditioning
agents with improved tolerability profiles, which we refer to as “improved conditioning agents,” which could be used in
connection with treatment with CASGEVY, significantly broadening the eligible SCD and TDT patient population. We are
also investigating in vivo gene-editing approaches and small molecules for the potential treatment of SCD and TDT.
Pain
Pain can be debilitating and develop from a variety of conditions. Most commonly, people with pain can be categorized
as suffering from one of three types of pain: acute pain, chronic neuropathic pain (caused primarily by damage or dysfunction
of peripheral nerves), or chronic musculoskeletal pain (caused primarily by damage to muscle, joints or bone). Acute pain
usually resolves in days or weeks (for example, following surgery or an injury), while chronic pain generally lasts greater
than three months due to unresolved or ongoing damage to tissues or nerves. Currently available treatments have limitations
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around efficacy or side effects, including a risk of addiction. Because of these challenges, over, under, and mis-utilization of
current pain medicines may occur.
The sodium channels NaV1.8 and NaV1.7 play important roles in the physiology of pain. We have discovered multiple
selective small molecule inhibitors of NaV1.8 as potential treatments for pain. We obtained pharmacological validation of
NaV1.8 inhibition with a first generation NaV1.8 inhibitor in acute pain, chronic neuropathic pain, and chronic
musculoskeletal pain.
Acute Pain
In August 2025, we announced results from the Phase 2 placebo-controlled dose-ranging clinical trial evaluating the
safety and efficacy of VX-993, an investigational selective NaV1.8 pain signal inhibitor, for the treatment of acute pain
following bunionectomy surgery. The clinical trial was powered to determine whether VX-993 would result in higher clinical
efficacy than previously demonstrated with the NaV1.8 pathway. Based on the efficacy results of the clinical trial, we did not
expect VX-993 to be superior to suzetrigine and therefore chose not to further advance VX-993 as monotherapy in acute pain.
VX-993 was generally safe and well-tolerated.
Peripheral Neuropathic Pain
There are no approved medicines in the U.S. that are labeled for the treatment of peripheral neuropathic pain. We are
evaluating suzetrigine, our selective non-opioid NaV1.8 pain signal inhibitor, for the treatment of DPN, a type of peripheral
neuropathic pain, in two Phase 3 clinical trials. We expect to complete enrollment in both Phase 3 clinical trials by the end of
2026. The FDA granted Breakthrough Therapy Designation to suzetrigine in DPN. We are also enrolling and dosing people
with DPN in a Phase 2 clinical trial evaluating VX-993.
In connection with our serial innovation approach, we are advancing multiple NaV1.8 inhibitors and NaV1.7 inhibitors,
which could be used alone or in combination, for the treatment of acute pain and peripheral neuropathic pain.
IgA Nephropathy
IgAN is a serious, progressive, life-threatening chronic kidney disease driven by uncontrolled autoreactive B cell activity
that causes inflammation and damage to the kidneys. It is the most common cause of primary glomerulonephritis worldwide.
We estimate that IgAN affects approximately 330,000 people in the U.S. and Europe, and, globally, more than 1.5 million
people are diagnosed with IgAN. A high percentage of people with IgAN progress to end-stage kidney disease.
IgAN is thought to occur when the body produces an abnormal form of IgA, a type of antibody that normally helps the
body fight infections. The body generates an abnormal immune response, including antibodies (autoantibodies), against this
abnormal IgA, and these antibodies can combine to create larger molecules called immune complexes. These immune
complexes can deposit in the kidneys, triggering damage and inflammation, especially within the glomeruli, impairing the
kidneys’ ability to properly filter waste and fluid.
We are developing povetacicept for multiple diseases and believe that it has pipeline-in-a-product potential. Povetacicept
is a potent dual inhibitor of the BAFF and APRIL cytokines, which promote B cell proliferation, differentiation and survival,
and provides B cell control by inhibiting the ability of BAFF and APRIL to drive the pathogenesis of multiple autoimmune
diseases, such as IgAN, pMN and generalized myasthenia gravis (“gMG”) (as described below). Povetacicept was
specifically engineered to achieve improvements in binding affinity, potency, pharmacokinetics, and tissue distribution.
Povetacicept has demonstrated potential best-in-class efficacy in a global Phase 1/2 clinical trial in people with IgAN. A
small volume dose of povetacicept is expected to be self-administered at home once every four weeks via a subcutaneous
auto-injector.
We completed enrollment in RAINIER, the global Phase 3 pivotal trial of povetacicept versus placebo in people with
IgAN. The clinical trial design contemplates a pre-planned interim analysis evaluating the change from baseline in urine
protein-to-creatine ratio (“UPCR”) after a certain number of patients reach 36 weeks of treatment. We expect to share data
from the interim analysis in the first half of 2026. If positive, the interim analysis may serve as the basis to seek accelerated
approval in the U.S. The final analysis will occur when patients reach two years of treatment and will evaluate total eGFR
(estimated glomerular filtration rate) slope. The FDA has granted Breakthrough Therapy Designation for povetacicept in
IgAN. We submitted the first module of the IgAN BLA to the FDA at the end of 2025 under the rolling submission pathway,
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and we expect to complete the submission in the first half of 2026, pending positive results from the interim analysis. We are
using a priority review voucher to expedite the FDA review of the povetacicept BLA from ten months to six months.
Our serial innovation approach continues with respect to IgAN and other B cell-mediated diseases.
APOL1-Mediated Kidney Disease
AMKD is a rapidly progressive, proteinuric kidney disease caused by variants in the APOL1 gene. In AMKD, the
kidney’s filtering units, known as the glomeruli, and within them the cells known as podocytes, are damaged, leading to
leakage of protein into the urine, deterioration in kidney function, scarring, and, ultimately, end stage renal disease. People
with AMKD progress to end stage kidney disease at a faster rate than those with other forms of chronic kidney disease and
reach kidney failure at a median age of 45 years old. AMKD occurs in people with African ancestry, with an estimated
patient population of approximately 150,000 people in the U.S. and Europe. In addition, we estimate that there are
approximately 100,000 people with AMKD with comorbidities, such as type 2 diabetes, in the U.S. and Europe.
In a Phase 2 proof-of-concept clinical trial, people with APOL1-mediated focal segmental glomerulosclerosis (“FSGS”)
treated with inaxaplin on top of standard of care achieved a statistically significant, substantial, and clinically meaningful
reduction of proteinuria. Inaxaplin was generally safe and well tolerated by patients. Based on the positive Phase 2 data, the
FDA granted Breakthrough Therapy Designation to inaxaplin for FSGS and the European Medicines Agency (“EMA”)
granted Priority Medicines (“PRIME”) designation to inaxaplin for AMKD. We initiated pivotal development of inaxaplin in
a single Phase 2/3 adaptive clinical trial (“AMPLITUDE”) in people with AMKD in 2022. We completed enrollment of the
interim analysis cohort of AMPLITUDE in 2025 and we expect to conduct the pre-planned interim analysis once this cohort
has been treated for 48 weeks. We expect to share data from the interim analysis in late 2026 or early 2027, and we expect to
complete full enrollment in the AMPLITUDE clinical trial in the second half of 2026.
Our serial innovation strategy in AMKD focuses on indication expansion: evaluating inaxaplin in new populations of
people with AMKD not included in the AMPLITUDE clinical trial. The Phase 2 clinical trial (“AMPLIFIED”) evaluates
inaxaplin as a treatment for people with AMKD with moderate proteinuria, or with AMKD and type 2 diabetes, two
populations that are not being studied in the AMPLITUDE trial. We expect to complete the AMPLIFIED clinical trial and
share results in mid-2026.
Type 1 Diabetes
T1D is a chronic metabolic disorder caused by insufficient insulin secretion by the beta cells in the pancreas. In people
with T1D, the insulin-producing islet cells of the pancreas are destroyed by the person’s own immune system, resulting in a
lack of insulin and impairment of blood glucose control. While insulin therapy allows patients to live for decades with the
disease, challenges of insulin therapy include inadequate control of blood sugar (both hyper- and hypo-glycemia), a
substantial burden of care on patients and families, and long-term vascular complications. Current standards of care do not
address the underlying causes of the disease, and there are limited treatment options beyond insulin for the management of
T1D.
We are developing non-autologous (allogeneic) fully differentiated, stem-cell derived islet cell therapies designed to
replace insulin-producing islet cells that are destroyed in people with T1D, with the goal of delivering a functional cure.
Zimislecel, our first program, is a stem cell-derived, allogeneic, fully differentiated, insulin-producing islet cell replacement
therapy, using standard immunosuppression to protect the implanted cells. We believe that zimislecel has the potential to
transform the lives of eligible people with T1D. In the U.S. and Europe, we estimate that there are approximately four million
people diagnosed with T1D. At initial launch, we expect there will be approximately 65,000 people with high unmet need
who experience severe hypoglycemic events who will be eligible for zimislecel.
We have completed enrollment in the Phase 1/2/3 clinical trial evaluating the safety and efficacy of zimislecel. We have
temporarily postponed completion of the dosing pending an ongoing internal manufacturing analysis. The most recent data
from this trial, published online in the New England Journal of Medicine in June 2025, continue to demonstrate the
transformative potential of zimislecel with consistent and durable patient benefit. The safety profile is generally consistent
with the immunosuppressive regimen used in the trial, the infusion procedure, and complications from long-standing
diabetes. Zimislecel has been granted Regenerative Medicine Advanced Therapy and Fast Track designations from the FDA,
PRIME designation from the EMA, Breakthrough Medicine designation from the Kingdom of Saudi Arabia (“Saudi
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Arabia”), and has secured an Innovation Passport under the Innovative Licensing and Access Pathway from the U.K.
Medicines and Healthcare products Regulatory Agency (the “MHRA”).
In March 2025, we announced results from the Phase 1/2 clinical trial evaluating VX-264, which encapsulated zimislecel
in an immunoprotective device. VX-264 was generally safe and well-tolerated but did not meet its efficacy endpoint, and we
have discontinued development of this program.
In connection with our serial innovation approach, we are pursuing research-stage programs to evaluate additional
approaches that could provide transformative benefits to people with T1D and reduce or eliminate the need for standard
immunosuppressive regimens, including targeting improved immunosuppression for zimislecel.
Primary Membranous Nephropathy
pMN is a serious, progressive, life-threatening chronic kidney disease driven by uncontrolled autoreactive B cell activity
that causes inflammation and damage to the kidneys. It is a rare autoimmune glomerular disease that occurs when the body
generates an abnormal immune response, including antibodies (autoantibodies), against proteins that are part of the kidney.
We estimate that pMN affects approximately 150,000 people in the U.S. and Europe, and more than 600,000 people globally.
Autoantibodies trigger damage and inflammation, especially within the glomeruli, impairing the kidneys’ ability to properly
filter waste and fluid.
People with pMN can experience a variety of serious complications, including blood clots, infection, and heart disease.
At time of diagnosis, most people with pMN are at risk of progression to end-stage renal disease. There are no therapies
specifically approved for the treatment of pMN.
We believe povetacicept represents a potentially best-in-class approach to control B cell activity in people with pMN.
We have received Fast Track Designation from the FDA and PRIME designation from the EMA for povetacicept in pMN.
Based on the strength of the Phase 2 results in the RUBY-3 clinical trial, we completed the End of Phase 2 meeting with the
FDA and reached agreement on an adaptive Phase 2/3 pivotal development program for pMN; we are enrolling and dosing
people with pMN in that clinical trial. We expect to complete the Phase 2 portion of the clinical trial and to initiate the Phase
3 portion of the trial in mid-2026.
Autosomal Dominant Polycystic Kidney Disease
ADPKD is a life-shortening genetic kidney disease characterized by the growth of numerous kidney-enlarging cysts that
impair kidney function and can ultimately lead to end stage renal disease. In most cases, ADPKD is caused by variants in the
PKD1 and PKD2 genes; the majority of ADPKD patients have a variant in the PKD1 gene. Around half of people with
ADPKD experience kidney failure by the age of 60. We estimate that there are approximately 300,000 people diagnosed with
ADPKD in the U.S. and Europe.
VX-407 is a first-in-class small molecule corrector that is designed to target the underlying cause of ADPKD in people
with a subset of PKD1 variants, which represents up to approximately 10% of the overall patient population living with
ADPKD. We are enrolling and dosing patients in a Phase 2 proof-of-concept clinical trial evaluating VX-407 (“AGLOW”)
for the treatment of ADPKD. We expect to complete enrollment in the AGLOW clinical trial by the end of 2026.
In connection with our serial innovation approach, we are progressing multiple research-stage assets in ADPKD.
Myotonic Dystrophy Type 1
DM1 is an inherited disease that results in the weakening and destruction of skeletal muscles over time. Muscle
weakness, muscle wasting and myotonia (sustained muscle contraction and difficulty relaxing muscles) are the hallmark
features of DM1. It is a serious life-shortening disease with no approved treatments, and we estimate that it affects
approximately 110,000 people in the U.S. and Europe.
VX-670, our lead approach for DM1, holds the potential to address the underlying cause of DM1. VX-670 is an
oligonucleotide connected to a cyclic peptide to promote effective delivery into cells. We continue to enroll and dose in the
multiple ascending dose portion of the global Phase 1/2 clinical trial of VX-670 in people with DM1 (“GALILEO”), which
evaluates both safety and efficacy of VX-670. We expect to complete enrollment and dosing in this trial in mid-2026.
Our serial innovation approach in DM1 includes a small molecule program in preclinical development.
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Generalized Myasthenia Gravis
gMG is a serious, chronic, and debilitating B cell-mediated immune disorder. This rare condition is caused by the
formation of pathogenic autoantibodies to key proteins that function in neuromuscular transmission. These pathogenic
antibodies block, alter, or damage the neuromuscular junction, which is the connection point between nerve cells and the
muscles they control. As a result, people with gMG experience muscle weakness and fatigue, which can lead to inability to
perform the activities of daily living and, in severe cases, compromise of respiratory muscles that can lead to life-threatening
respiratory failure. Current therapies address only subsets of the gMG population, and many advanced treatments require
cyclic treatment and drug holidays due to safety challenges and immunosuppression. As a consequence, there is significant
unmet medical need for improved therapies. We estimate that gMG affects approximately 175,000 people in the U.S. and
Europe and more than 300,000 people globally.
Povetacicept is a potent dual inhibitor of BAFF and APRIL, two cytokines that are elevated in gMG, where they play
distinct roles in the proliferation, differentiation, and survival of B cells. In gMG, elevated expression of both BAFF and
APRIL drives uncontrolled B cell growth and activation, triggering overproduction of the pathogenic autoantibodies driving
disease activity. By inhibiting both BAFF and APRIL, we believe povetacicept represents a potential best-in-class approach
to reducing production of these pathogenic autoantibodies in gMG.
We expect to initiate a placebo-controlled, Phase 2 dose-ranging proof-of-concept clinical trial evaluating povetacicept
for the treatment of people with gMG in the first half of 2026.
STRATEGIC TRANSACTIONS
As part of our business strategy, we seek to license or acquire technologies, products, product candidates, and businesses
that are aligned with our corporate and research and development strategies and that complement and advance our ongoing
research and development efforts. In addition, we establish business relationships with collaborators to support our research
activities and to lead or support development and/or commercialization of certain product candidates. We expect to continue
to identify and evaluate potential acquisitions, licenses and collaborations that may be similar to or different from the
transactions that we have engaged in previously.
Acquisitions
In 2024, we acquired Alpine for approximately $5.0 billion. Alpine’s lead molecule, povetacicept, is a highly potent and
effective dual inhibitor of BAFF and APRIL. We are currently evaluating povetacicept in a pivotal trial as a potentially best-
in-class approach to treat IgAN. We also believe povetacicept holds pipeline-in-a-product potential for other indications, such
as pMN and gMG.
We previously made other acquisitions which have expanded and advanced our pipeline, including:
•In 2019, we established our T1D program through our acquisition of Semma, a privately held company focused on
the use of stem cell-derived human islets as a potentially curative treatment for T1D. We are evaluating zimislecel
for the potential treatment of T1D in a Phase 1/2/3 clinical trial.
•In 2017, we enhanced our CF portfolio through our acquisition of certain CF assets, including deutivacaftor, from
Concert Pharmaceuticals Inc. In 2024, the FDA approved ALYFTREK for people with CF 6 years of age and older.
We expect to continue to identify and make acquisitions to expand and advance our pipeline and business.
Collaboration and Licensing Arrangements
Joint Development and Commercialization Agreement with CRISPR
In 2017, we entered into a joint development and commercialization agreement (“Original JDCA”) with CRISPR
Therapeutics AG (“CRISPR”), pursuant to which we are co-developing and co-commercializing CASGEVY for SCD and
TDT. In 2021, we and CRISPR amended and restated the Original JDCA (the “A&R JDCA”).
Pursuant to the A&R JDCA, we lead global development, manufacturing and commercialization of CASGEVY, with
support from CRISPR. Subject to the terms and conditions of the A&R JDCA, we have the right to conduct all research,
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development, manufacturing, and commercialization activities relating to the product candidates and products under the A&R
JDCA (including CASGEVY) throughout the world, subject to CRISPR’s reserved right to conduct certain activities.
The net profits and net losses incurred pursuant to the A&R JDCA with respect to CASGEVY are allocated 60% to us
and 40% to CRISPR, subject to certain adjustments, while all other product candidates and products under the A&R JDCA
have net profits and net losses shared equally between the parties.
Either party may terminate the A&R JDCA upon the other party’s material breach, subject to specified notice and cure
provisions, or, in our case, in the event that CRISPR becomes subject to specified bankruptcy, winding up, or similar
circumstances. Either party may terminate the A&R JDCA in the event the other party commences or participates in any
action or proceeding challenging the validity or enforceability of any patent that is licensed to such challenging party
pursuant to the A&R JDCA. We also have the right to terminate the A&R JDCA for convenience at any time after giving
prior written notice.If circumstances arise pursuant to which a party would have the right to terminate the A&R JDCA on
account of an uncured material breach, such party may elect to keep the A&R JDCA in effect and cause such breaching party
to be treated as if it had exercised its opt-out rights with respect to the products associated with such uncured material breach
and the royalties payable to the breaching party would be reduced by a specified percentage.
Either party may opt out of the development of a product candidate under the A&R JDCA after predetermined points in
the development of the product candidate, on a candidate-by-candidate basis. In the event of such opt-out, the party opting-
out will no longer share in the net profits and net losses associated with such product candidate and, instead, the opting out
party will be entitled to high single to mid-teen percentage royalties on the net sales of such product, if commercialized.
In-License Agreements
We have entered into various agreements pursuant to which we have obtained access to technologies from third parties
and are conducting research and development activities with collaborators. Pursuant to these arrangements, we have obtained
development and commercialization rights to resulting product candidates. Depending on the terms of the arrangements, we
may be responsible for the costs of research activities, required to make upfront payments and/or milestone payments upon
the achievement of certain research, development, and commercial objectives, and/or pay royalties on future sales, if any, of
commercial products resulting from the collaboration. Our current in-license agreements include:
•CRISPR Therapeutics AG. In addition to our arrangement with CRISPR described above, we have exercised options
to exclusively license treatments for specific targets, including CF, that were subject to the research program under
the collaboration agreement we entered into with CRISPR in 2015. In 2019, we obtained exclusive worldwide rights
to CRISPR’s intellectual property for Duchenne muscular dystrophy (“DMD”) and DM1 gene-editing products
through a new agreement with CRISPR. In 2023, we obtained non-exclusive rights to CRISPR’s intellectual
property for the development of hypoimmune gene-edited cell therapies for T1D through a new agreement with
CRISPR.
•Moderna, Inc.In 2016, we entered into a collaboration with Moderna for the identification and development of
mRNA therapeutics encoding CFTR for the treatment of CF. We are evaluating VX-522, an mRNA therapeutic,
pursuant to this collaboration.
•Entrada Therapeutics, Inc. In 2022, we established a collaboration with Entrada focused on enabling efficient
intracellular delivery of an oligonucleotide for DM1. This collaboration includes VX-670, an investigational
candidate for the treatment of DM1 that is in clinical development. We are evaluating VX-670 in people with DM1
pursuant to this collaboration.
Out-license Agreements
We have entered into various agreements pursuant to which we have out-licensed rights to certain product candidates to
third-party collaborators. Pursuant to these out-license arrangements, our collaborators are responsible for certain costs
related to the continued development of such product candidates and obtain development and commercialization rights to
these product candidates. Depending on the terms of the arrangements, our collaborators may be required to make upfront
payments, milestone payments upon the achievement of certain research and development objectives and/or pay royalties on
future sales, if any, of commercial products licensed under the agreement.
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In 2025, we entered into agreements with Zai Lab Limited (“Zai”) and Ono Pharmaceuticals Co., Ltd (“Ono”) related to
the development and commercialization of povetacicept in certain Asian markets. Zai licensed povetacicept for mainland
China, Hong Kong SAR, Macau SAR, Taiwan region, and Singapore, while Ono licensed povetacicept for Japan and South
Korea. Zai and Ono will help advance povetacicept clinical trials and will be responsible for obtaining marketing
authorizations and commercialization activities in the licensed territories, if povetacicept becomes an approved product.
Cystic Fibrosis Foundation
In 2004, we entered into an agreement (the “CFF Agreement”) with the Cystic Fibrosis Foundation (the “CFF”), as
successor in interest to the Cystic Fibrosis Foundation Therapeutics, Inc., to support research and development activities.
Pursuant to the CFF Agreement, as amended, we have agreed to pay tiered royalties ranging from single digits to sub-teens
on covered compounds first synthesized and/or tested during a research term on or before February 28, 2014, including
ivacaftor, lumacaftor and tezacaftor, and royalties ranging from low-single digits to mid-single digits on net sales of certain
compounds first synthesized and/or tested between March 1, 2014 and August 31, 2016, including elexacaftor. We do not
have any royalty obligations on compounds first synthesized and tested on or after September 1, 2016. For combination
products, such as ORKAMBI, SYMDEKO/SYMKEVI, TRIKAFTA/KAFTRIO, and ALYFTREK, sales are allocated
equally to each of the active pharmaceutical ingredients in the combination product, and royalties are then paid for any
royalty-bearing components included in the combination. For TRIKAFTA/KAFTRIO, the CFF Agreement does not identify
a specific date on which royalty obligations terminate. To qualify as a royalty bearing “Drug Product” as defined under the
CFF Agreement, a compound must be covered by intellectual property protection (including patents) that Vertex has the legal
right to license to another party.
INTELLECTUAL PROPERTY
Patents and other intellectual property rights such as trademarks, trade secrets, and copyrights are critical to our business.
We actively seek protection for our products and proprietary information by means of U.S. and foreign patents, trademarks,
and copyrights, as appropriate. In addition, we rely upon trade secret protection and contractual arrangements to protect
certain of our proprietary information.
Patents provide a period of exclusivity that can make it more difficult for competitors to market and use our technology.
We own and control patents and pending patent applications that relate to compounds, formulations, synthetic routes,
intermediates, devices, treatment of diseases, and other inventions.
To protect our intellectual property, we typically apply for patents several years before a product receives marketing
approval. Under current law, a patent expires 20 years from its first effective filing date. Since the drug development process
may last for many years, there may be a period of time in which we have an issued patent but not marketing approval to sell
the drug. To compensate for patent term lost while a product is in clinical trials and undergoing review for marketing
approval, we may be able to apply for patent term extensions or supplementary protection certificates (“SPCs”) in some
countries. In addition to patent protection, we receive regulatory exclusivity from U.S. and European regulatory agencies for
the active pharmaceutical and biological agents and, where applicable, their approved orphan indications for a certain time
period. Regulatory exclusivity runs concurrently with patent exclusivity and provides complementary protection for our
products.
For our approved commercial products, and those in development, we own or hold exclusive and non-exclusive licenses
to several hundred patents around the world. In the U.S., once a New Drug Application (“NDA”), or a supplement thereto, is
approved we are required to list with the FDA each U.S. patent with claims that cover our product or a method of using the
product. The FDA publishes the patents we list in a book referred to as the Orange Book. We have fourteen issued U.S.
patents listed in the Orange Book that cover the active pharmaceutical ingredients in KALYDECO, its marketed
formulations, and/or its approved indication. We have 22 issued U.S. patents listed in the Orange Book that cover the active
pharmaceutical ingredients in ORKAMBI, its marketed formulations, and/or its approved indication. We have 25 issued U.S.
patents listed in the Orange Book that cover the active pharmaceutical ingredients in SYMDEKO, its marketed formulations,
and/or its approved indication. We have 34 issued U.S. patents listed in the Orange Book that cover the active pharmaceutical
ingredients in TRIKAFTA, its marketed formulations, and/or its approved indication. We have 35 issued U.S. patents listed
in the Orange Book that cover the active pharmaceutical ingredients in ALYFTREK, its marketed formulations, and/or its
approved indication. We have an issued patent listed in the Orange Book that covers the active pharmaceutical ingredient in
JOURNAVX, its marketed formulation, and/or its approved indication.
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Products approved by the FDA under a BLA, including CASGEVY, receive 12 years of regulatory exclusivity in the
U.S. from a product’s approval date. Additionally, we have licenses to dozens of issued U.S. patents that cover CASGEVY,
its approved indication, and/or its manufacture. Products approved by the FDA under a BLA are not subject to the Orange
Book patent listing requirement.