Companies that foster an environment that supports professional growth are more likely to thrive and successfully adopt digital innovation. Here are the 100 best places to work in Europe—and how they stay that way.

Vertex Pharmaceuticals ranks 94 on Fortune 100 Best Companies to Work For – Europe 2026 list.

Fortune 100 Best Companies To Work For – Europe

With a combined revenue of $21 trillion and $2.1 trillion in profits, the 2026 Fortune 500 is the definitive list of America's largest companies.

Fortune 500

This year's 100 Best Companies to Work For are rebuilding the social contract at work so people feel supported, trusted, and future-ready as they undergo that transition.

100 Best Places to Work 2026_Vertex Pharmaceuticals Inc

Employees say:"Vertex is a company that truly cares, from the top down, about the mission for bringing transformative therapies to patients and about its employees. The benefits offered here are unparalleled, as are the opportunities for growth and development. This is a truly special place to be."

Fortune 100 Best Companies to Work For

See which workplaces made this year's list.

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Employees say:&nbsp;"The Vertex 101 and other scientific and commercial learning series is awesome! The 'leading edge' is also a great connection point for the average employee that is appreciated and 'humanizes' the C-Suite. Finally, the continued learning series that provides development in management and job skills is one of a kind and shows the investment Vertex makes for its employees as workers and people in general."

Best Large Workplaces in Biotechnology and Pharmaceuticals

Almost $20 trillion in revenue—and a record-breaking $1.87 trillion in profits. Introducing the 2025 Fortune 500, the definitive list of the biggest companies in America.

The top companies on our list have one thing in common: Staff largely trust leadership to see them as well-rounded people and reward them for a job well done.

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Employees say: "This organization is like none other. Patients are at the center of everything we do. Secondly, the care and compassion we have for each other, both personal and professional, is unprecedented in the industry. The executive team and management are always seeking ideas and ways to innovate process to better serve the patients and the team."

The companies on this annual list make a conscious effort to be supportive, inclusive workplaces.

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Employees say:"I love the professional, mutual respect, and care for the employees that is demonstrated on a daily basis. The commitment to patients and focus on innovation across all departments, make it very easy to be committed to and passionate about our work. In addition, the truly inclusive and diverse culture, is very modern and refreshing."

100 Best Large Workplaces for Women

GPTW BioPharma Large 2024-Vertex Pharmaceuticals Inc

Employees say:"This organization is like none other. Patients are at the center of EVERYTHING we do. Secondly, the care and compassion we have for each other, both personal and professional is unprecedented in the industry. The executive team and management is always seeking ideas and ways to innovate process to better serve the patients and the team."

Fortune partners with global people analytics firm Great Place to Work to analyze survey feedback representing employees from companies across the U.S.

GPTW Millennials-2024-Vertex Pharmaceuticals Inc_US1__20240522184224_4

Employees say:"Vertex makes products that are truly life-changing for patients. People here recognize the importance of what we do, work hard, and are always looking for ways to do things better. Leadership recognizes the value of the employees and goes the extra mile to give recognition and ensure that the benefits we receive are at the top of our industry."

100 Best Large Workplaces for Millennials

Industries included in the sector are insurance and managed care, medical products and facilities, pharmacy services, and pharmaceutical companies.

Fortune Sector Leaders: Health Care

The Fortune 500, in its 70th year in 2024, ranks the biggest U.S. companies by revenue.

Creating a more empathetic workplace looks like staying loyal to workers, emphasizing D&I initiatives, and paying well.

100 Best Companies 2024-Vertex Pharmaceuticals Inc

Vertex, a global biotechnology company, invests in the scientific pursuit of medicines and treatments for serious diseases. It currently has ongoing clinical and research programs that treat underlying causes of cystic fibrosis, and recently <a href="https://www.nytimes.com/2024/01/30/health/vertex-pain-medicine-non-opioid.html">announced</a> progress toward a nonopioid investigational drug to treat moderate to severely acute pain.&nbsp; &nbsp;Flexible remote work, two weeks off in addition to paid vacation time, and commuting benefits are on the list of employee benefits. The company also encourages employees to get involved in volunteer opportunities by organizing an annual Global Day of Service, through which the company matches up to $5,000 per year to nonprofits of an employees’ choosing. The group’s CEO, Reshma Kewalramani, hosts small gatherings of employees through a meeting she calls Lemonade and Pretzels, to answer employee questions.&nbsp;

The 200 companies on this list are transforming industries from the inside out.

America's Most Innovative Companies

Building a culture of trust and transparency is essential to help everyone thrive, especially in rocky economic times.

100 BEST COMPANIES 2023-Vertex Pharmaceuticals Inc

The global biotechnology company invests in innovation in order to develop medicines for people with serious diseases. The company culture values recognizing the efforts of its employees. 
<ul> 
 	<li>When a major milestone is achieved, such as the FDA approving one of its medicines, Vertex brings in patients who will benefit from the drug, along with their families, to share their stories and ring a giant antique fire bell to commemorate the occasion.</li> 
 	<li>New managers take part in Lead, a 12-week immersive leadership development program designed to better help them manage a team.</li> 
 	<li>The company offers global synchronous days off, where all employees are off at the same time, ideally meaning no overflowing inbox or missed deadlines when they return, letting them truly enjoy the time away. Additionally, all of Vertex shuts down for two weeklong periods each year, letting employees focus on themselves, spend time with loved ones, and recharge.</li> 
 	<li>The company’s mentoring program uses a matching tool to facilitate pairings based on how closely aligned a mentee’s development goals are to a mentor’s strengths. As a result, people with different lived experiences and perspectives are connected, and mentors grow from the experience as well.</li> 
</ul>

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Employees say: 
 
"The company goes out of their way to ensure employees are allowed to have non-work time—like creating 'synchronous days' so that people taking a day off will not be bothered by others still working that day. They also make sure to engage the employees with all major accomplishments and have regular formal and informal discussions across employee groups to ensure all voices are heard."

GPTW Women 2023-Vertex Pharmaceuticals Inc

Employees say: 
 
"Vertex is nothing like anywhere I've ever worked. When you walk into the building, you can just feel that something special is happening there. It has a 'pulse' of people passionate about helping patients and innovating at high speeds. It is a privilege to work here!"

Fortune partnered with Great Place to Work to analyze survey feedback representing nearly half a million U.S. employees.

GPTW Millennial Large 2023-Vertex Pharmaceuticals Inc

Employees say: 
 
"People care about each other. The management cares about employees with great benefits about work-life balance! The work we do means a great deal to a lot of people/patients, and I'm so proud to work here!"

The Fortune 500, in its 69th year in 2023, ranks the biggest U.S. companies by revenue.

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Employees say: 
 
“This company puts our own personal career development as a higher priority than any other place I have worked. I have never done an individual development plan at any other company, never worked at a place that offered gigs and rotations like Vertex does, or had some many opportunities to work on side projects that align with my own interests. Our benefits are also unmatched in my experience, the stock offerings, opportunities for bonuses, health coverage (HSA particularly), and maternity leave as well as commuter benefits are incredibly generous.”

GPTW Women 2022-Vertex Pharmaceuticals Inc

Employees say: 
 
“This company puts our own personal career development as a higher priority than any other place I have worked. I have never done an individual development plan at any other company, never worked at a place that offered gigs and rotations like Vertex does, or had some many opportunities to work on side projects that align with my own interests.”

This year’s Fortune 500 marks the 68th running of the list.

This year’s Fortune 500 marks the 67th running of the list.

The biopharmaceutical company makes its debut on the Fortune 500 this year, riding the wave of a 49% year-over-year revenue increase in 2020—driven primarily by its cystic fibrosis drugs Kaftrio and Trikafta.

Collectively, the ranked companies produced a three-year average shareholder return of 33%, vs. 19% for the S&P 500.

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100 Fastest-Growing Companies

Explore this year's ranking of the 50 companies with the best long-term growth potential.

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In the fall of 2019, Vertex launched Trikafta, the latest of its breakthrough therapies for people with cystic fibrosis. Capable of treating up to 90% of those who suffer from the progressive, life-threatening disease, the drug has already been used to treat thousands of patients in the U.S. and recently won approval in the EU. The company’s sales—$4.2 billion in 2019—have averaged 35% annual growth over the past three years. One setback: The biotech’s stock fell 23% in October after it scrapped a new drug in Phase II clinical trials.

The Future 50

This year's Fortune 500 marks the 66th running of the list.

Collectively, the ranked companies produced a three-year average shareholder return of 19%, vs. 11% for the S&P 500.

Fastest Growing Companies 2020-06-Vertex Pharmaceuticals

Fortune's proprietary methodology allows us to zero in on the 50 global firms that are best poised to deliver—and continue delivering—above average gains.

This year's Fortune 500 marks the 65th running of the list.

Welcome to the inaugural Fortune Future 50, our new ranking of companies best positioned for breakout growth.

This year's Fortune 500 marks the 64th running of the list.

Fastest-growing Companies

Revenue 3 Yr Growth Rank

Revenue 3 Yr Annual Growth Rate

EPS 3 Yr Growth Rank

EPS 3 Yr Annual Growth Rate

Total Return 3 Yr Rank

Total Return 3 Yr Annual Rate

Beat S&P 500 3 Yr Return

Current Streak

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Future 50

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Best Workplaces For Women

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Free mental health sessions (per year)

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Maximum $ amount covered for fertility services

Fully paid maternal leave (days)

Fully paid paternal leave (days)

Fully paid adoptive leave (days)

Maternal leave in addition to regular time off (days)

Paid days off for volunteering

Best Workplaces In Biopharma

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Best Companies To Work For Europe

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GPTW national list

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Vertex Pharmaceuticals, a biotechnology company, develops and commercializes therapies for serious chronic conditions such as cystic fibrosis, which damages the lungs, digestive system, and other organs. Vertex also developed Casgevy, one of two gene therapies approved for the treatment of sickle cell anemia, a rare and painful blood disorder. Casgevy is also the first FDA-approved therapy that utilizes CRISPR/Cas9 genome editing technology.

Q2 2026

Q1 2026

Q4 2025

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Q2 2025

Q1 2025

Q4 2024

Vertex Pharmaceuticals (VRTX): Company Profile, Stock Price, News, Rankings

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Vertex Pharmaceuticals

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Good day, and welcome to the Vertex Pharmaceuticals Fourth Quarter 2025 Earnings Call. All participants will be in a listen-only mode. Should you need assistance, please signal a conference specialist by pressing the star key followed by zero. After today's presentation, there will be an opportunity to ask questions. Please note this event is being recorded. I would now like to turn the conference over to Ms. Susie Lisa. Please go ahead.

Good evening, everyone. My name is Susie Lisa, and as Senior Vice President of Investor Relations, I'd like to welcome you to our fourth quarter and full-year 2025 financial results conference call. On tonight's call, making prepared remarks, we have Dr. Reshma Kewalramani, Vertex's CEO and President, Charlie Wagner, Chief Operating Officer and Chief Financial Officer, and Duncan McKechnie, Chief Commercial Officer. We recommend that you access the webcast slides as you listen to this call. The call is being recorded, and a replay will be available on our website. We will make forward-looking statements on this call that are subject to the risks and uncertainties discussed in detail in today's press release and in our filings with the Securities and Exchange Commission.

These statements, including without limitation, those regarding Vertex's marketed medicines for cystic fibrosis, sickle cell disease, beta thalassemia, and moderate to severe acute pain, our pipeline and Vertex's future financial performance, are based on management's current assumptions. Actual outcomes and events could differ materially. I would also note that select financial results and guidance that we will review on the call this evening are presented on a non-GAAP basis. I'll now turn the call over to Reshma.

Thank you, Susie. Good evening, all, and thank you for joining us on the call today. 2025 was marked by excellent progress across the business, disciplined commercial execution in CF and the new product launches, meaningful pipeline progress, and robust financial performance. Fourth quarter results wrapped up another strong year, with 10% total revenue growth, and for the full year 2025, total revenue growth was 9%. As we executed on our plans for commercial diversification, full-year 2025 results included CASGEVY revenue of $116 million and JOURNAVX's revenue of $60 million in the eight months since launch. Building on the momentum of our Q4 and full-year 2025 results, in 2026, we are focused on increasing the number of patients we serve and further diversifying our revenue base.

2026 priorities include expanding leadership in CF, accelerating adoption of CASGEVY, growing JOURNAVX, both in prescriptions and revenue, and advancing the emerging renal franchise, starting with Pove in IgAN. We are entering an exciting period, and Vertex is well positioned to deliver on the significant opportunities in front of us and drive sustained growth over the long term by combining commercial execution with serial innovation and rapidly advancing the pipeline across multiple serious disease areas. With that overview, I'll focus my R&D comments tonight on cystic fibrosis and the renal franchise. Beginning with cystic fibrosis, ALYFTREK is a next generation 2.0 CFTR modulator and is the fifth approved CF therapy in our portfolio. ALYFTREK brings many important benefits for patients: once daily dosing, regulatory approval in additional mutations, and the best CFTR protein function restoration in our CF portfolio.

As continued evidence of this, I am pleased to share the top-line results from the recently completed ALYFTREK phase III trial, this one in two- to five-year-olds. All patients in this study were on TRIKAFTA and switched to ALYFTREK on entry into the study. ALYFTREK was safe and well tolerated, and the sweat chloride data showed a mean reduction of 9.6 mmol from a TRIKAFTA baseline. Importantly, 65% of these ALYFTREK patients achieved levels of sweat chloride below the normal or carrier level of 30 mmol when treated through 24 weeks. This compares to 37.5% of patients at normal levels of sweat chloride at baseline on TRIKAFTA. This magnitude of sweat chloride reduction is unprecedented for this age group in cystic fibrosis.

We are on track to initiate global regulatory submissions for ALYFTREK in the two- to five-year-old age group in the first half of this year. As we continue to march down to younger age groups, I'm also pleased to share that the ALYFTREK one- to two-year-old study has already initiated and enrollment and dosing are underway. Turning now to our next wave of CFTR modulators or next-gen 3.0 medicines. In this class, VX-828 is the most efficacious corrector we have ever studied in vitro and advanced to studies in patients. The VX-828 proof of concept study is on track to complete enrollment and dosing in the first half of 2026. VX-581, another corrector from this 3.0 class, is currently in a phase I healthy volunteer study. Beyond these two assets, we are advancing additional CF regimens.

Shifting to the VX-522 program. For the approximately 5,000 patients who do not make any CFTR protein and therefore cannot benefit from our CFTR modulators, our phase I/II study of VX-522 is on track for readout in the second half of this year, and we aren't stopping there. We are poised to continue to expand our CF leadership position, driven by more than 20 years of serial innovation, an enduring goal that if it is possible to do better for our CF patients, we are committed to doing so, an unmatched 200,000+ patient years of real-world data, and a proven ability to extend the benefits of our medicines to the youngest patients. Moving next to our renal pipeline, which is emerging as our fourth vertical, alongside CF, heme, and pain, as a key engine for Vertex's next decade of growth.

Povetacicept, a dual BAFF/APRIL inhibitor, is the most advanced asset in our renal pipeline, with the first expected indication in IgA nephropathy or IgAN. IgAN is a progressive kidney disease with high unmet need that affects 330,000 people in the U.S. and Europe, and more than 1 million people in Asia. We see Pove's dual BAFF/APRIL inhibition as key to interdicting the underlying cause of IgA nephropathy, because this is a disease driven by B cells, and BAFF and APRIL are the key cytokines that play distinct roles in B cell proliferation, differentiation, and survival. In addition to mechanism of action, Pove's biophysical characteristics enable a differentiated profile. Pove was specifically engineered to achieve improvements in binding affinity, potency, pharmacokinetics, and tissue distribution. This protein engineering translates to two key areas of downstream advantage.

First, in terms of efficacy, through phase II, pove has delivered substantial reductions in proteinuria and stabilization in GFR, supported by significant reductions in Gd-IgA1 and hematuria. As importantly, povetacicept's meaningful advantages in dosing. Povetacicept is administered as a once-monthly, small-volume, subcutaneous dose delivered via an auto-injector, a noteworthy consideration in the chronic biologics market, where ease of use has repeatedly been shown to influence product choice. Pove's progressing through the BLA regulatory pathway, where FDA's granted breakthrough therapy designation as well as rolling review. We used a priority review voucher to ensure an expedited timeline for regulatory review and initiated our rolling BLA submission by submitting the first module in December of 2025. We remain on track to complete the BLA submission in the first half of this year if the phase III interim analysis results are supportive.

Switching to Pove and membranous nephropathy, a disease that affects approximately 150,000 patients in the U.S. and Europe and over 400,000 patients in Asia, where we've partnered with Zai and Ono for these markets, as we did in IgAN. Membranous nephropathy, like IgAN, carries significant morbidity and lacks disease-modifying therapies. Accordingly, pove has FDA Fast Track and EMA PRIME designations and was recently granted Orphan Drug Designation in the U.S. The OLYMPUS phase II/III adaptive study of pove in membranous is enrolling and dosing patients. I'm pleased to share we remain on track to complete the phase II portion of this study and advance to phase III this summer.

Before updating you on the two other renal programs in mid and late-stage clinical development, let me shift focus briefly to neurology and pove's potential as a pipeline and a product with our plans in generalized myasthenia gravis. The rationale to study pove myasthenia is compelling. First, it's a serious disease with high morbidity. Second, there are approximately 175,000 patients with myasthenia in the U.S. and Europe, and an estimated 300,000 patients globally. Third, current therapies have limitations in terms of mechanism of action, specificity, or the need for cyclical administration. This need for cyclical administration is particularly challenging, as it can lead to disease relapse and progressive damage to neuromuscular junctions. In contrast, pove is dosed chronically and does not require cycling on and off. Lastly, recent human clinical pharmacology results provide strong evidence for dual BAFF/APRIL inhibition as a transformative approach.

Putting this all together, we believe pove's mechanism of action and specifically engineered protein format provide best-in-class potential in myasthenia. I am pleased to share that we're on track to initiate a proof of concept phase II dose-ranging study of pove in myasthenia in the first half of 2026. Now, returning back to renal and inaxaplin for APOL1-mediated kidney disease, or AMKD, where we completed enrollment in the interim analysis cohort of the AMPLITUDE pivotal study last fall. We anticipate several key upcoming inaxaplin milestones. First, completing enrollment in the AMPLITUDE full clinical trial cohort in the second half of this year. Second, results from the AMPLITUDE interim analysis cohort either late this year or early next, and if the results are positive, to file for U.S. accelerated approval thereafter.

Finally, in the Amplified study of inaxaplin in patients with AMKD and moderate proteinuria, or patients with AMKD and type 2 diabetes, patient groups we did not study in AMPLITUDE, we expect results in mid-2026. The last program in renal to cover tonight is VX-407, which is being studied in a phase II proof of concept trial for autosomal dominant polycystic kidney disease, or ADPKD. This disease affects 300,000 patients in the U.S. and Europe, with no available disease-modifying treatments. VX-407 is a small molecule protein-folding corrector that targets the underlying cause of disease in up to 10% of people with ADPKD. The VX-407 phase II proof of concept study is up and running, and we expect to complete enrollment this year.

This study will evaluate the effect of VX-407 on height-adjusted total kidney volume, an important efficacy outcome, given that it's an FDA-accepted surrogate endpoint in ADPKD. I'll close with two quick updates on a couple of other R&D programs. For CASGEVY, we remain on track to file for U.S. approval in patients ages five to 11 in the first half of this year. Recall, this has been granted a Commissioner's National Priority Voucher, and thus, we expect an expedited review. For JOURNAVX in acute pain, a pair of single-arm JOURNAVX phase IV studies have been recently completed and will be presented at medical conferences this spring. One in aesthetics and reconstructive procedures and another in laparoscopic and arthroscopic procedures.

In both studies, JOURNAVX was used as part of multimodal pain therapy. The first study in plastic surgery procedures showed approximately 90% of patients remained opioid-free versus less than 10% opioid-free rates in the literature with standard of care for similar procedures. In the second study, which included arthroscopic knee and shoulder procedures, as well as laparoscopic procedures, 76% of JOURNAVX patients remained opioid-free versus less than 50% opioid-free rates in the literature with standard of care for similar procedures. And in chronic neuropathic pain, our two suzetrigine phase III studies in patients with diabetic peripheral neuropathy remain on track to complete enrollment by the end of this year. With that, I'll turn the call over to Duncan to review the commercial highlights.

Thanks, Reshma. The focus of the commercial organization in 2025 was to drive multiple successful launches, fueled by clear strategic intent, disciplined execution, and targeted investments. We launched ALYFTREK in the U.S. and Europe, built momentum behind the launch of CASGEVY in the U.S., Europe, and the Middle East, and successfully executed on the first year of launch for JOURNAVX here in the U.S. We're pleased with the progress we're making to diversify our revenue growth and treat patients in four diseases around the world. In cystic fibrosis, our goal has been to help patients get to carrier or normal levels of CFTR function as measured by sweat chloride. We've made incredible progress against this goal for patients with all mutations, all age ranges, and all geographies.

We now have five approved CFTR modulators, a decade plus of real-world evidence, over 77,000 patients on one of our CF therapies, and access agreements in over 60 countries across six continents. We continue to drive growth from new patients, new launches, new geographies, and new reimbursement agreements, all supported by an underlying 3% annual increase in the CF population over the last five years. Focusing now on ALYFTREK. The rollout in the U.S. and Europe continues to progress well. The vast majority of treatment-naive patients in countries where we have reimbursement are already on ALYFTREK. We also see continued ongoing transitions from TRIKAFTA to ALYFTREK, and the majority of ALYFTREK scripts continue to come from switches. ALYFTREK's improved sweat chloride profile and once-daily dosing versus TRIKAFTA are resonating with the clinical community, even as we observe strong patient loyalty to TRIKAFTA.

In Europe, we have already secured reimbursed access for ALYFTREK in key countries, for example, England, Ireland, Germany, Denmark, and Norway. We also recently announced reimbursement for ALYFTREK in Australia, New Zealand, and Italy, the latter enabling access for 1,500 patients to a CFTR modulator for the first time. Additionally, we continue to make excellent progress expanding geographically with meaningful contributions in 2025 from Brazil and Turkey. Overall, 2025 was another year of strong execution and growth in CF, and we will continue these efforts into 2026. Key drivers of growth for CF in 2026 include continuing the launch of ALYFTREK globally, treating younger patients, expanding to additional geographies, securing access for patients, and maintaining our comprehensive patient support programs.

Turning now to CASGEVY, where we successfully moved from a foundational year in 2024 to a year of building significant momentum in 2025. You can see the evidence of this acceleration in our excellent quarter four 2025 results, where CASGEVY had 111 new patient initiations, 37 patients with first cell collections, and 30 patients receiving infusions, driving $54 million in quarterly revenue. We also reached some notable reimbursement agreements for CASGEVY in quarter four 2025. In the U.S., more than 30 states have joined the CMS Cell and Gene Therapy Access Model, and there is now approximately 90% access for both Medicaid and commercial CASGEVY patients, with the remainder having case-by-case access.

In Europe, all countries in the U.K. are now providing reimbursed access, and a recent landmark coverage decision by the Italian reimbursement body represents about 5,000 eligible TDT patients, half of Europe's beta thalassemia population. We anticipate seeing continued quarter-to-quarter variability in CASGEVY infusions in 2026, based on the duration of the patient journey and given the fact that patients themselves dictate when they wish to receive their infusion. We anticipate this will smooth out in 2027 and beyond, as the number of patients at all stages of the treatment journey continues to build. Overall, we're very encouraged by the robust flow of patients in the U.S., in Europe, and the Middle East, moving from referral to cell collection and infusion as we drive towards realizing CASGEVY's multibillion-dollar potential. Moving to pain.

I'm pleased to report that JOURNAVX achieved our 2025 launch objectives of, firstly, securing broad payer access, secondly, ensuring extensive hospital adoption, and thirdly, creating a broad prescriber base across both the hospital and retail segments. This launch strategy was designed to create a strong long-term foundation for years of growth with JOURNAVX. More than 550,000 JOURNAVX prescriptions were filled in 2025, with a roughly 50/50 split between hospital and retail channels. There were as many prescriptions written in the fourth quarter of 2025 as there were in the prior three quarters cumulatively. Although I would note that quarter four revenue growth does not yet fully reflect this strong prescription growth, given the continued utilization of our patient support programs.

Importantly, more than 35,000 physicians wrote prescriptions for JOURNAVX in 2025, including orthopedic surgeons, general surgeons, anesthesiologists, pain specialists, dentists, and general practitioners. Over 200 million lives now have access across all three national PBMs. In addition, 21 states now provide unrestricted access for Medicaid recipients without prior authorization or step edit requirements. JOURNAVX has also been incorporated into formularies, order sets, and/or discharge protocols across more than 950 hospitals and over 100 integrated delivery networks, a significant accomplishment in a short period of time and an indicator of the unmet need in this space. Perhaps most importantly, we estimate that about 420,000 Americans benefited from the inclusion of JOURNAVX in their treatment journey as an effective, well-tolerated non-opioid option for moderate to severe acute pain.

Looking ahead, given the strong adoption of JOURNAVX by hospitals and physicians and the progress we've made in securing payer coverage, we plan to double the size of our field force in quarter two. We will also continue with a range of consumer engagement activities to drive meaningful prescription and revenue growth in 2026. This includes the recent launch of our first Vertex-connected TV campaign in January, which we are piloting in select markets. In 2026, we expect to more than triple the number of JOURNAVX prescriptions compared to the approximately 550,000 written in 2025. As we work to finalize access and gain coverage with additional payers, including Medicare Part D plans, we have made the strategic decision to maintain the patient support program for those patients not covered by their insurance.

As this PSP program sunsets and gross to net normalizes in late 2026, early 2027, we expect prescription growth to increasingly drive meaningful revenue growth, especially in the latter half of the year. Our expectation is that JOURNAVX gross to net will ultimately settle at levels comparable to other branded medicines. We're excited to continue to drive a transformation in the management of the 80 million Americans with moderate to severe acute pain each year by offering a safe and effective non-opioid treatment option and to build another multi-billion-dollar franchise for Vertex. Turning now to our emerging renal business. We are partnering with and investing in the nephrology community for the long term, and povetacicept is the first in a series of potentially transformative medicines that tackle the underlying cause of several renal diseases: IgAN, PMN, AMKD, and ADPKD.

We anticipate that the renal franchise will ultimately rival the scale of our CF business, and we're seeking to bring the best elements of our success in CF to these kidney disease areas. These best practices include an intense focus on the patient, an unrelenting commitment to serial innovation in R&D, a clear high science sell to specialist physicians, and disciplined execution in securing reimbursed access here in the U.S. and around the world. We will also offer comprehensive patient support programs for eligible patients to remove access challenges and enable them to more seamlessly obtain the medicine their HCPs prescribe. We believe our experience, focus, and capabilities equip us to win in renal and deliver substantial value to both patients and healthcare providers. Povetacicept's potential best-in-class profile enables us to clearly distinguish it within the IgA nephropathy landscape, setting it apart from other therapies.

As Reshma detailed, Pove is an engineered fusion protein designed specifically to address B cell-mediated autoimmune diseases with a strong clinical profile that is further supported by an easy-to-use, small-volume auto-injector administered at home every four weeks. The importance of this insight has been borne out in our recent research with nephrologists, who highlight the importance of payer access and preference for an auto-injector versus prefilled syringe in their treatment decisions. This market research with nephrologists reinforces what we've seen in the biologic space many times over. Commercial excellence, combined with patient convenience and ease of use of the medicine, are critical drivers of market share. We began preparing for povetacicept's launch last year by building a commercial team for renal and engaging payers to ensure broad access.

We're completing the staffing of our teams, and the first contingent of our field team is already trained and actively engaging customers and providing disease education. As noted above, we're also developing a comprehensive renal patient support program based on our decade plus of experience supporting cystic fibrosis patients. In summary, each of our commercialization areas reflects a clear strategic intent and an ambitious approach to both established and future launches. Our 2025 performance positions the portfolio for continued revenue growth, deeper market penetration, and, most importantly, broader patient impact across cystic fibrosis, hematological disorders, moderate to severe acute pain, and potentially, in the future, multiple renal diseases. I'll now turn the call over to Charlie for our financial results and outlook.

Thanks, Duncan. I'm pleased to share the details of Vertex's strong financial performance in the fourth quarter and for the full-year 2025, which stands as a testament to our market leadership, the strength of our product portfolio, and our disciplined approach to investment and operational management. In the fourth quarter, total revenue reached $3.2 billion, a 10% increase compared to Q4 2024. For the full year, total revenue was $12 billion, an increase of 9% versus 2024. These results reflect our consistent commercial execution, durable CF franchise strength, and expansion into new high-value disease areas. Our cystic fibrosis therapies remain the foundation of our revenue and cash flow, with full-year 2025 growth of 7% globally.

CF revenue in the U.S. grew 11% year-over-year, largely due to pediatric uptake, ongoing strength in TRIKAFTA and ALYFTREK, higher realized net prices, and a modest benefit from channel inventory in the fourth quarter. Internationally, CF revenue grew 2% year-over-year, reflecting the ongoing penetration of KAFTRIO in established markets and contributions from ALYFTREK in countries where reimbursed, partly offset by the previously communicated $200 million decline in Russia sales for the year. CASGEVY achieved $54 million in revenue in Q4 and $116 million for the full year 2025, and during Q4, demonstrated continued momentum in patient initiations and first cell collections. JOURNAVX delivered $27 million in sales in the fourth quarter and $60 million for the full year, with substantial growth in quarterly prescriptions since its launch in Q1 of 2025.

Note that JOURNAVX gross to net was significantly impacted by our patient support program in 2025, and that impact will diminish over the course of 2026. Our increasingly diversified commercial portfolio, now spanning four disease areas, is driving new revenue streams and adding to our near and long-term growth profile. Our fourth quarter gross margin of 85.7% reflects this product mix, as well as investment in manufacturing optimization for our diversifying portfolio. I would add that Q4 gross margin is a reasonable proxy for what to expect in 2026. Turning to operating expenses, Q4 2025 combined non-GAAP, R&D, acquired IPR&D and SG&A expenses totaled $1.4 billion, up 5% year-over-year, and reflect our strategic investments in product launches, principally in pain and late-stage pipeline programs.

Fourth quarter non-GAAP operating expenses included $56.5 million of IPR&D expense, or approximately $0.22 per share. This fourth quarter BD activity included an exclusive global license agreement with WuXi Biologics to develop and commercialize a tri-specific T-cell engager for B cell-mediated autoimmune diseases. This asset is currently in preclinical development. For the full year, combined non-GAAP, R&D, acquired IPR&D and SG&A expenses totaled $5.1 billion, consistent with our previous guidance. Excluding acquired IPR&D, the increase versus prior year was primarily driven by the acceleration of late-stage clinical programs in renal medicine and ongoing expansion of commercial and marketing activities to support the launch of JOURNAVX and upcoming launches in renal.

The fourth quarter 2025 non-GAAP effective tax rate was 13.5%, reflecting increased utilization of one-time tax credits and our full-year 2025 non-GAAP effective tax rate was 17.3%. Q4 2025 non-GAAP net income was $1.3 billion, up 24% year-over-year, delivering $5.03 of earnings per share, up 26% versus the prior year. Full-year 2025 non-GAAP net income of $4.7 billion resulted in $18.40 of EPS. Vertex ended 2025 with $12.3 billion in cash, cash equivalents and marketable securities. Our strong balance sheet positions us to continue investments in both internal and external innovation. During 2025, we increased our repurchase activity, buying approximately 4.8 million shares for roughly $2 billion.

This reflects our ongoing commitment to returning value to shareholders while maintaining the flexibility to act on growth opportunities. Let me now turn to guidance for 2026. We expect full-year 2026 total company revenue to be in the range of $12.95 billion-$13.1 billion, representing 8%-9% growth versus the prior year. This outlook anticipates continued solid performance from our CF franchise and a $500 million or greater revenue contribution from non-CF products, including greater volumes of patient infusions for CASGEVY and a ramp of JOURNAVX prescriptions. In Q1 2026, we anticipate year-over-year total revenue growth of approximately 7%, with growth accelerating thereafter and building towards our full-year guidance.

Additionally, we expect combined non-GAAP operating expenses to be in the range of $5.65 billion-$5.75 billion as we continue to invest in our late-stage clinical pipeline and commercial build outs in support of new launches and revenue diversification, particularly for genetics in acute pain and for renal. We anticipate our non-GAAP effective tax rate to be in the range of 19.5%-20.5% for 2026, as we do not expect a repeat of the one-time tax benefits we experienced in 2025. In addition, based on our understanding of current rules, we do not expect a material impact from tariffs given our diversified supply chain and large U.S. manufacturing presence, but this outlook is subject to change.

In summary, 2025 was a year of very strong performance, continued execution on our commercial priorities and clinical programs, and further strengthening of our robust financial foundation. As we turn to 2026 and beyond, Vertex remains well positioned to continue expanding our impact for patients, investors and all stakeholders. We look forward to updating you on our progress on future calls, and I'll now ask Susie to begin the Q&A period.

We will now begin the question-and-answer session. To ask a question, you may press star then one on your touchtone phone. If you're using a speakerphone, please pick up your handset before pressing the keys. To withdraw your question, please press star then two. Our first question will come from Cory Kasimov with Evercore ISI. Please go ahead.

Great. Good afternoon. Thanks for taking my question. Probably not surprising that it's on pove. Curious how you view the risk of potential hypogammaglobulinemia adverse events and how this could ultimately impact the label, if at all. Thank you.

Cory, this is Reshma. Let me take that one. On hypogammaglobulinemia, that's to say, low IgG levels. The way BAFF/APRIL inhibitors work, you're going to see a decrease in IgG. It's part and parcel of the mechanism of action. But the important question you're asking is, what does that mean, if anything, on safety? So the data that we've shown is RUBY-3, the 80 mg RUBY-3 cohort that we showed at ASN in November. What you see there is there were actually no SAEs, none of infection. It doesn't matter what IgG level you look at, there were simply none. That's good news. There was a single patient with IgG levels of less than 300 mg. That was a threshold we used. It was not associated with any serious infection, and there was no severe infection either.

And on average, when you look at the IgG levels from the RUBY-3 IgAN study, the average value was within the normal limit range, so let's say, around 700 mg. When I look at that, I don't really see anything there. I think that when you look at the overall benefit risk, including IgG levels, but look at everything as a whole, it looks really very good. I hope that helps.

Very helpful. Yeah, very helpful. Thank you, Reshma.

The next question will come from Salveen Richter with Goldman Sachs. Please go ahead.

Good afternoon. Thanks for taking my question. With regard to the guidance here, is there any way you could help us understand what's baked into the guide for the CF component relative to ALYFTREK and TRIKAFTA? And on ALYFTREK in particular, you had a strong quarter, so walk us through the contributing factors here as we think of the trajectory for 2026. Thank you.

Salveen, I'm going to split that question and ask Charlie to go first on the guide, and then I'll ask Duncan to comment on the market dynamics that led to the Aly numbers we shared.

Yes, Salveen, no, no additional color on the guidance. Obviously, total revenue guidance of $1.295 billion-$1.301 billion, so 8%-9% for the year. Within that, a contribution, a non-CF contribution of $500 million or more. Within CF, we're not going to break it down further in terms of Aly versus other products. Maybe Duncan can comment on the dynamics in Aly that we're seeing right now.

Sure. Thanks for the question, Salveen. So I'd say the fourth quarter was buoyed by the international launch. So we, as you know, secured reimbursement in Europe, in countries like the U.K., Germany, Denmark, Ireland, Norway, in 2025. So that really helped drive some of the numbers that we saw in the latter part of 2025, and we expect that to continue obviously into 2026.

Thank you. The next question will come from Geoff Meacham with Citibank. Please go ahead.

Hey, guys. Thanks for the question. Just have a couple. The first one, you guys seem really excited about pove's potential as well as the renal space. I guess the question is, is there work to do on the payer side when you think about access and reimbursement and, and maybe cost benefit? When you look historically, rare renal hasn't been a category where you get higher realized value, but obviously a new MOA can help that. Then just a follow-up on Aly. Is there more interest in the US in, in using sweat chloride as a disease biomarker? And, and you mentioned the European launch. I mean, how would you characterize maybe the awareness and willingness to switch, to, to Aly compared to the U.S.? Thanks.

All right, Geoff, I'm going to ask Duncan to comment on both, but we'll take it in two parts. Let's do Aly first, Duncan. How do folks, how does the community think about sweat chloride, U.S. versus ex-U.S.? How do you see the uptake? And then let's get to pove. Geoff, you are absolutely right to detect a ton of enthusiasm in our voice on pove. It's not just about pove and IgAN, but it's pove in membranous nephropathy and in myasthenia gravis. And it is getting close to the time where we think we're going to have the results to share and close to the time where we think we're going to be able to file. So enthusiasm is certainly building internally. Duncan, on the pove question, it was about reimbursement and how you're seeing that.

Thanks for the question, Geoff. So as far as the interest in sweat chloride is concerned, in general terms, from a physician level, the level of sort of understanding and interest in the connection between sweat chloride and CFTR function is by and large, similar, in the U.S. to Europe. There are no major differences in that regard. In terms of your question about willingness to switch, as you know, there are some different dynamics with regard to the labeling, between the U.S. and Europe, meaning that there are fewer liver function and liver monitoring requirements in Europe, so that has an impact on the dynamic.

The other comment I would make as well is we've always seen more rapid uptake in naive patients, and as per the prepared remarks, there are, for example, 1,500 naive patients in Italy that have just been reimbursed for a CFTR modulator for the first time ever. So we would anticipate rapid uptake in that particular patient population. On the first part actually of your question, povetacicept and our engagements with payers and the payer community, I would make just a couple of comments. Firstly, we started engaging with the payers in July last year. We've, at this point, had 74 engagements with multiple payers that cover over 210 million lives, and I would say those conversations are going extremely well.

They are very well educated on IgAN, and they are very interested in the products that are coming to the market. So we feel really good about where we're at with our engagements with payers so far, and where those will go in the future.

The next question will come from Tazeen Ahmad with Bank of America. Please go ahead.

Hi, guys. Good afternoon. Thanks for taking my question. With relation to pove, can we talk about what you're expecting to show on proteinuria? Like, what results do you think would provide, in your mind, medically, clinically differentiated data versus competitors? Thanks.

Sure. Magnitude of proteinuria response. I think we've talked about this before, but in every study that we've done, the depth of proteinuria response, the greater the depth, the better it is in terms of long-term outcomes. Long-term outcomes being defined as death, dialysis, or time to transplantation. In this particular interim analysis, I would point you to the RUBY-3 80 mg IgAN results. I think it's the best analog to look at to sort of get a sense for what we could see from the RAINIER trial. I say that because it's very similarly designed in the inclusion and exclusion criteria, the proteinuria threshold, the GFR threshold for entry. It's the same exact dose, 80 mg, and the endpoint is exactly the same. In RUBY-3, the 36-week proteinuria data was a 56% reduction in proteinuria.

Vertex Pharmaceuticals (VRTX) Q4 2025 Earnings Call Transcript

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