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

Years on List

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Future 50

Overall Score

Culture rank

Process rank

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Best Workplaces For Women

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Founded

# Work Sites

Best Companies

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Subsidized childcare

Compressed work weeks

Option to work remotely

Minimum requirement in-office attendance (days per week)

Mental health coverage

Free mental health sessions (per year)

Free backup childcare time off (days)

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

Sites

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Profit Ratios

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Best Companies To Work For Europe

CEO/Top executive

Group headquarters

HQ location

GPTW national list

Woman CEO

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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

Q3 2025

Q2 2025

Q1 2025

Q4 2024

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

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Vertex Pharmaceuticals

vertex pharmaceuticals

Good day, and welcome to the Vertex Pharmaceuticals' third quarter of 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, ma'am.

Good evening, all. My name is Susie Lisa, and as the Senior Vice President of Investor Relations, it is my pleasure to welcome you to our third quarter 2025 financial results conference call. On tonight's call, making prepared remarks, we have Dr. Reshma Kewalramani, Vertex's CEO and President, Duncan McKechnie, Chief Commercial Officer, and Charlie Wagner, Chief Operating and Financial 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.

Thanks, Susie. Good evening, all, and thank you for joining us on the call today. Vertex delivered strong performance across the board in Q3, with $3.08 billion in revenue reflecting double-digit growth versus Q3 2024. As we continue to extend our leadership in CF, we're also diversifying our revenue base by product and by geography with the growing global momentum of CASGEVY and the broad uptake of Jurnavix in acute pain across a wide range of prescribers, pain types, and settings of care. Concurrently, we are forward planning for the fourth vertical of Vertex's growth, centered on renal diseases and povetacicept in multiple indications, starting with POVI in immunoglobulin A nephropathy, or IGAN. Moving to the pipeline and starting with CF, our long-standing goals in CF have been threefold. One, bring forward a medicine that can treat CF patients who make some amount of CFTR protein.

Two, bring forward a medicine that restores CFTR function to normal levels, as measured by sweat chloride, and to do so from as early in life as possible so patients have the potential to live a long and healthy life like people who carry just one CF allele. And three, bring forward a medicine for the last 5% of CF patients who do not make any CFTR protein at all. We are making progress on all three fronts. First, Aliftrack treats more mutations than Trikafta. The number of patients newly eligible for a CFTR modulator that treats the underlying cause of their disease is approximately 400 more patients in the U.S. and approximately 4,000 more patients in the E.U. than Trikafta. In total, 95% of all patients are eligible or will be eligible for Aliftrack as we make our way to lower age groups.

Second, Aliftrack, which launched in the U.S. late last year and is launching in Europe now, has seen a strong response from patients and physicians who are excited for a once-daily medicine that can bring sweat chloride levels down in patients ages six plus to the lowest levels achieved of any CFTR modulator in this age group. Two additional points to make on sweat chloride. We recently completed the pivotal study for Trikafta for the one to two-year-old patient population, and the results are remarkable. The study's primary endpoint was safety, and the data were consistent with the established safety profile of this medicine. The secondary endpoint was reduction in sweat chloride. The baseline sweat chloride was about 100 millimoles per liter, and over the course of the 24-week study, there was a mean reduction of more than 70 millimoles per liter from baseline through week 24.

Furthermore, nearly 70% of patients in the study achieved levels of sweat chloride below the 30 millimoles per liter threshold, the level considered normal. This magnitude of sweat chloride improvement is unprecedented and the largest reduction we have seen with any CFTR modulator in any population to date. We are on track to make global regulatory submissions for Trikafta in this population of one to two-year-olds in the first half of 2026. Additionally, as we serially innovate, we continue to develop new CFTR regimens with the aim of reaching our long-standing objective of bringing the majority of patients of any age with CF to normal levels of sweat chloride. As I just discussed with the Trikafta one to two-year-old study, we are already there in our youngest patients.

In our Alyftrek phase 3 study of six to 11-year-olds, more than 50% of patients got to normal levels of sweat chloride. VX-828, our next-gen 3.0 CFTR corrector, is the most efficacious we have ever studied in vitro to enter the clinic. I am pleased to share we have now initiated the CF cohort in the VX-828 study. And third, regarding our final goal, VX-522, which we're developing for the 5,000 or so patients who cannot benefit from our CFTR modulators, we have resumed enrollment and dosing in the MAD portion of that phase 1/2 study. Moving then to pain. In acute pain, during the quarter, we completed enrollment in two phase 4 trials evaluating Jurnavix, initiated preoperatively and as part of multimodal approaches to acute pain management.

The interim analysis for one study will be shared at a medical conference later this week, and top-line results for Jurnavix show safety and efficacy consistent with the pivotal program, accompanied by substantial reductions in opioid use following aesthetic or reconstructive procedures, with approximately 90% of participants being opioid-free compared to less than 10% after similar procedures, per the literature. In neuropathic pain, the first DPN phase three study is well underway, and we have completed work that sets up the initiation of the second DPN phase three study later this month. Transitioning now to the kidney portfolio. Renal medicine is experiencing a renaissance in drug development, and Vertex seeks to be a leader in the field. With our differentiated R&D approach, grounded in causal human biology, validated targets, and biomarkers that translate, we have a broad portfolio of innovative therapies with transformative potential for patients with serious kidney diseases.

Our clinical pipeline has first-in-class or best-in-class assets for four kidney diseases, three of which are already in or approaching pivotal development: VX-407 for autosomal dominant polycystic kidney disease, or ADPKD. Inaxaplin for APOL1-mediated kidney disease, or AMKD. POVI for IGAN. And POVI for primary membranous nephropathy. Starting with VX-407 for ADPKD, where the phase 2 proof of concept study was initiated earlier this quarter. Recall there are approximately 300,000 patients with ADPKD in the U.S. and Europe. These patients have limited treatment options and no approved therapies that treat the underlying cause of this disease. We believe that up to 10% of patients with ADPKD may be eligible for treatment with VX-407, a first-in-class, small-molecule protein-folding corrector. VX-407 is designed to target the root cause of ADPKD by restoring PC1 protein function.

This phase 2 proof of concept study is a single-arm trial of 24 patients that evaluates the effect of VX-407 on height-adjusted total kidney volume. The second kidney program to highlight is Inaxaplin for primary AMKD, a disease that affects 150,000 patients in the U.S. and EU. Enrollment in the interim analysis cohort of the Amplitude pivotal study has completed. The patients in this cohort are now being treated for 48 weeks, after which we will conduct the interim analysis, and if positive, we will be poised to submit for potential accelerated approval in the U.S. Additionally, we are running the Amplified study, which is a phase 2 proof of concept study of Inaxaplin in patients with AMKD with moderate proteinuria or patients with AMKD and diabetes, populations not being studied in the Amplitude trial. Amplified is on track to complete enrollment by the end of this year.

Now turning to povetacicept. The lead and first indication for POVI is IGAN, a disease impacting more than 300,000 diagnosed patients in the U.S. and Europe and over 1 million patients globally. There are four points to highlight in this program. First, we completed enrollment of the interim analysis cohort of the Rainier phase three trial earlier this year. Second, the FDA has granted POVI breakthrough therapy designation and rolling review for our BLA. Third, we have completed the studies to support the launch of POVI for at-home self-administration with a subcutaneous autoinjector. Lastly, the new news I'm very pleased to share tonight is that we have completed full enrollment in the Rainier phase three trial. The trial enrolled approximately 600 patients in approximately 15 months, the fastest of any contemporary phase three study in IGAN, and is a testament to the significant opportunity ahead for POVI.

Here's the outlook when you put these four major milestones together. With the rolling review that the FDA has granted, we will begin our submission for potential accelerated approval before the end of this year. Once the interim analysis cohort completes 36 weeks of treatment, assuming the results are positive, we will complete our BLA submission for potential accelerated approval in the U.S. in the first half of 2026. We have used a priority review voucher, and thus we have certainty that POVI's BLA in the IGAN indication will receive an expedited priority review in the U.S. That is a six-month review versus a traditional 10-month review. Next, and consistent with this pipeline and product potential, we are pleased to have initiated the pivotal study for the second potential renal indication for POVI in primary membranous nephropathy.

There are approximately 150,000 patients with membranous nephropathy in the U.S. and Europe and nearly 500,000 globally. Today, there are no approved therapies that treat the underlying cause of this disease, leaving a significant patient population with high unmet need. POVI was recently granted Fast Track designation by the FDA in membranous nephropathy, and our phase 2/3 adaptive study Olympus is now underway. One final note in R&D regarding Zamylacell in Type 1 Diabetes. While we have completed enrollment in the pivotal trial for T1D, we have temporarily postponed completion of dosing while we work through an internal manufacturing analysis. As this is an ongoing pivotal trial, it is critical to maintain study integrity, and so we won't be providing any additional detail. I look forward to updating you once dosing is complete.

In closing, Vertex now has seven commercialized medicines, five programs in phase three development, and an exciting earlier stage R&D pipeline. Accordingly, as we drive to achieve our R&D milestones, we're executing on the concurrent work of getting our approved medicines to more patients around the globe and preparing for additional near-term potential launches. To tell you more about our commercial efforts, I'll now turn over the call to Duncan.

Thanks very much, Reshma. I will focus my comments tonight on the CF franchise, global launches of Aliftrack and Casgevy, the U.S. launch of Jurnavix, and commercial planning for our potential launches in four serious kidney diseases, the first of which will be POVI in IGAN. Beginning with CF, our CF franchise delivered strong double-digit growth this quarter as we continue to grow the number of eligible patients taking our CFTR modulators.

This reflects the ongoing launch of Alyftrek, progress with younger patients and patients with rare mutations, enhanced survival benefits of our therapies, and expansion into new geographies such as Brazil and Turkey. Focusing on Alyftrek, our fifth therapy approved to treat the underlying cause of CF. We believe Alyftrek is the best CFTR modulator available for eligible patients, given that when compared to standard of care Trikafta, Alyftrek provides further improvements in CFTR function, as measured by sweat chloride, is indicated for additional rare mutations, and offers the convenience of once-daily dosing. The U.S. launch of Alyftrek is progressing well across all patient groups. We have seen particularly rapid uptake in those patients who are naive to CFTR modulators, and the vast majority of previously untreated patients in the U.S. have now been initiated on Alyftrek.

We also see continued uptake by those patients who have previously discontinued one of our other CFTR modulators. Lastly, the pace of transition patients, primarily those switching from Trikafta, remains steady and represents the majority of patients on Aliftrack in the quarter. Outside the U.S., the early launch of Aliftrack is off to a strong start in multiple European countries where patients have reimbursed access: England, Ireland, Germany, and Denmark. And the feedback has been very positive, both in terms of the clinical profile and once-daily dosing. And as Reshma mentioned, there are nearly 10 times as many newly eligible patients in Europe with rare mutations for Trikafta and Aliftrack than in the U.S., and no additional liver monitoring requirements.

Overall, we are pleased with the response to Aliftrack and continue to expect that the majority of patients around the globe will transition to Aliftrack over time, given its multiple benefits. Moving to Casgevy, our transformative one-time treatment for patients with severe sickle cell disease and beta thalassemia. The momentum continues to build as we enter the last few months of 2025. As a result, we have a clear line of sight to over $100 million in Casgevy revenue this year and significant growth in 2026. Importantly, we have seen continued progress in securing access to Casgevy around the world, with the notable recent addition of reimbursement in Italy for TDT and SCD. Italy has the second-largest population in the world of TDT patients, at approximately 5,000 patients, about half of whom are eligible for Casgevy.

As further evidence of Casgevy building momentum across all three regions, the U.S., Europe, and the Middle East, I'm pleased to report that since launch and through the end of quarter three 2025, nearly 300 patients have been referred by their physicians to an ATC to initiate the treatment process. More than 160 patients now have had their first cell collection. This includes 110 in the first nine months of 2025, double our full year 2024 total, and a total of 39 patients have received their infusions of Casgevy-edited cells, including 10 patients in the third quarter of 2025. We see continued growth in ATCs onboarding and initiating patients in the U.S., Europe, and the Middle East as the treatment teams become more familiar with the process.

Through the end of September, 25 ATCs had initiated more than five patients, and at least one ATC in each of the three regions had initiated 20 or more patients. Given the very well-understood duration of the treatment journey and the fact that we now have significant numbers of patients at every stage in the process, Casgevy has a strong outlook, and we are excited to serve the growing numbers of patients through the end of this year, into 2026, and beyond. Now shifting to the launch of Jurnavix in moderate to severe acute pain. We continue to see a very positive reaction to this novel, non-opioid option for the treatment of moderate to severe acute pain. As a reminder, our goals in 2025 were firstly, secure broad payer coverage. Secondly, ensure hospital and health system access through P&T reviews and formulary adoption.

And thirdly, drive broad usage of Jurnavix across a range of physician and pain types with a seamless experience for physicians and patients alike. We're executing well on all fronts, and I'll now provide some details. We continue to make good progress with payers. As of mid-October, across commercial and government payers, over 170 million lives have reimbursed access to Jurnavix, up from the 150 million we discussed on our Q2 call. With commercial payers, our negotiations continue to progress favorably. We have formal coverage under two of the three large national PBMs and are working to add the third. In Medicare, we continue to engage with plans to secure coverage. And for Medicaid patients, through mid-October, we now have a total of 19 states, up from 16 last quarter, that are providing access to Jurnavix without prior authorization or step edit requirements.

We continue to expect that coverage across commercial, Medicare, and Medicaid payers will expand through the balance of 2025 and into 2026. Note that even after national payers grant formal coverage for Jurnavix, it can take time to ensure that all lives are covered in their downstream plans. Therefore, we plan to extend our patient support program, or PSP, into 2026 to ensure that if a physician makes the decision to prescribe Jurnavix for their patient with acute pain, the patient will receive the medicine. Recall, the PSP only kicks in for those patients without coverage or with highly restricted coverage, so if a patient's plan reimburses Jurnavix, the PSP program is not triggered. Secondly, we're making excellent progress with P&T committees at the approximately 150 healthcare systems and 2,000 hospitals we're targeting.

More than 750 hospitals and approximately 90 of the 150 targeted large healthcare systems have now added Jurnavix to their formularies, protocols, or order sets. Thirdly, we continue to see broad adoption of Jurnavix by a wide range of physicians, including orthopedic surgeons, plastic surgeons, anesthesiologists, pain specialists, and dentists. They are using Jurnavix in a wide range of pain settings, including surgical and non-surgical procedures such as joint replacement and repair, shoulder surgeries, fractures and sprains, and dental procedures. In hospital systems and clinics that have adopted Jurnavix, we have received impressive feedback from physicians in terms of very significantly reduced or eliminated opioid usage, consistent with the phase four study results Reshma mentioned earlier. Reports from patients also continue to be very positive in terms of how well Jurnavix managed their pain, in addition to being well tolerated.

We also continue to see that Jurnavix is promotionally responsive to our field representative calls, as well as our digital engagement with physicians. There is a clear correlation between frequency of calls and depth of prescription writing by physicians. For these reasons, and as we discussed last quarter, we're planning to add 150 additional representatives in the first quarter of 2026, which will enable us to increase our frequency of calls with existing prescribers and expand our coverage to additional physicians, and to raise awareness of Jurnavix among consumers, we have a wide range of communication initiatives ongoing, including a partnership with basketball superstar Jayson Tatum, as he shares his Jurnavix treatment journey experience post his Achilles injury during the playoffs last season.

Finally, as evidence of the growing reception in the marketplace, there have now been more than 300,000 prescriptions filled for Jurnavix across the retail and hospital settings as of mid-October. We continue to have high confidence that there is a significant unmet need for an effective non-opioid option to treat moderate to severe acute pain, and we're in the early days of creating another multi-billion dollar franchise for Vertex. I'll close with some comments on our commercial planning for our potential launches in renal medicine, where we have begun the build-out of our commercialization team. We expect that our renal franchise will become a significant growth driver and value generator for Vertex over the next several years. I'll focus my comments this evening on our first step in that direction, POVI in IGAN. We believe that POVI offers a unique combination of attributes with a compelling clinical and patient profile.

Firstly, POVI is a fusion protein specifically engineered for better tissue penetration and to deliver optimized, targeted dual inhibition of the BAFF and APRIL cytokines. In the Ruby 3 clinical data we've seen to date, POVI delivers substantial reductions in Gd-IgA1, hematuria, and proteinuria. Secondly, among the APRIL-only or dual BAFF-APRIL inhibitors, POVI has the most convenient dosing and administration for patients. Every four weeks, at-home administration via a subcutaneous autoinjector and the lowest dosage volume of less than 0.5 milliliters. Thirdly, POVI is the only dual BAFF-APRIL inhibitor in pivotal trials for multiple serious kidney diseases, IGAN and PMN. We believe POVI has a superior mechanism of action, a superior clinical profile, and will deliver a superior patient experience. In short, we believe POVI holds best-in-class potential.

We're excited to build out our renal franchise and prepare for commercialization in our fifth disease area with POVI as a potential best-in-class treatment for IGAN. I'll now turn the call over to Charlie to review the financials.

Thanks, Duncan. Vertex's Q3 2025 double-digit revenue growth demonstrates our consistent, strong performance and attractive growth profile. Third quarter 2025 total revenue increased 11% year-over-year to $3.08 billion. U.S. revenue growth of 15% year-over-year was driven in CF by ongoing patient demand and favorable net pricing versus prior year, as well as contributions from Aliftrack, Casgevy, and Jurnavix. Revenue outside the U.S. grew 4% year-on-year, including mid-single-digit CF growth and a contribution from Casgevy. Included in Q3 2025 total global revenue and the regional growth rates was $17 million of Casgevy revenue and $20 million from Jurnavix.

Third quarter 2025 combined non-GAAP R&D, acquired IP R&D, and SG&A expenses were $1.28 billion, compared to $1.08 billion in the third quarter of 2024. Non-GAAP operating expenses increased 19% year-on-year, driven primarily by the continued advancement of our broad later-stage pipeline, including the acceleration of POVI development programs, as well as the build-out of commercial capabilities in pain. Acquired IP R&D expenses were $55 million, compared to $15 million in the third quarter of 2024. Third quarter 2025 non-GAAP operating income was $1.38 billion, compared to $1.31 billion in the third quarter of 2024. Third quarter 2025 non-GAAP effective tax rate was 17.6%, including benefits from R&D tax credits as a result of last year's Alpine acquisition. Third quarter 2025 non-GAAP net income was $1.24 billion, compared to $1.14 billion in Q3 of 2024.

Third quarter 2025 non-GAAP earnings per share were $4.80, an increase of 10% compared to $4.38 in the third quarter of 2024. We ended the quarter with $12 billion in cash and investments after deploying approximately $1.1 billion to repurchase more than 2.7 million shares in the third quarter. Year to date, we have spent over $1.9 billion to repurchase approximately 4.5 million shares. Our priorities for cash deployment remain unchanged. Innovation and growth fueled by investments, both internal and external, with a second priority of share repurchases. Now switching to guidance. With only one quarter remaining in 2025, we are updating our financial guidance for revenue, operating expenses, and taxes. We now expect 2025 total revenue to be in a range of $11.9-$12 billion versus prior guidance of $11.85-$12 billion, representing growth of approximately 8%-9% for the full year at current exchange rates.

This outlook reflects our expectation for continued growth from our portfolio of CF medicines, including the ongoing launch of Aliftrack in the U.S. and recent launches in Europe. As Duncan mentioned, full-year revenue guidance also includes over $100 million of CASGEVY revenue as we treat more patients in geographies where we have secured regulatory approval and reimbursement. In addition, guidance reflects further contribution from Jurnavix in the fourth quarter due to growing prescription volumes. We are also refining guidance for combined non-GAAP R&D, acquired IP R&D, and SG&A expenses, and now expect operating expenses of approximately $5-$5.1 billion versus prior guidance of $4.9-$5 billion for the full year. This is primarily due to the acceleration in POVI development programs across multiple indications and increased investment in commercial and marketing activities to support the launch of Jurnavix.

There is no change to our estimate of approximately $100 million in projected IP R&D charges for the full year, including the recently announced collaboration with Enlaza. We continue to expect an immaterial cost impact from tariffs in 2025, based on what we know today, due to our significant U.S. presence and our geographically diverse supply chain. Of course, given the dynamic nature of the tariff situation, including the potential for sector-specific tariffs, this outlook is subject to change. And finally, we are lowering our expected full-year 2025 non-GAAP effective tax rate guidance from a range of 20.5%-21.5% to a revised range of 17%-18% to incorporate several one-time tax benefits. These benefits include those recognized in Q3 from Alpine-related R&D tax credits, as well as anticipated recognition in Q4 2025 of previously deferred tax benefits.

In closing, Vertex yet again delivered strong results in Q3 2025, growing and diversifying our revenue with the launch of two new products in the U.S., Aliftrack and Jurnavix, the launch of Aliftrack in Europe, and the continued global launch of CASGEVY. We also made significant pipeline progress across the portfolio in mid and late-stage clinical development, including POVI's pipeline and product potential and continued advancement. These and other anticipated milestones of continued progress in multiple disease areas are detailed on slide 17. We look forward to updating you on our progress on future calls. I'll now ask Susie to begin the Q&A.

Thanks, Charlie, and apologies, we understand there were issues with the webcast, and for that, we're sorry. We're working with our vendor for this call. We'll also look to get the transcript out as soon as possible. Chuck, can you please give the Q&A instructions?

Yes, ma'am. We will now begin the question-and-answer session. To ask a question, you may press Star then One on your touch-tone phone, and if you're using a speakerphone, please pick up your handset before pressing the keys. To withdraw your question, please press Star, then Two. And at this time, we'll pause momentarily to assemble our roster. And the first question will come from Geoff Meacham with Citigroup. Please go ahead.

Hey, guys. Afternoon. Thanks for the question. Just have two quick ones. On Aliftrack, just wanted to get maybe a bit of a status update. Do you think you're hitting a tipping point with regard to kind of patient switching or those that are maybe kind of new starts? And just curious about the monitoring requirement, whether that's sort of eased a little bit. And then the second thing is, as you guys look forward, Reshma, I know you're a nephrologist by training, so as you get closer to the POVI data set, maybe just help us with kind of how you're thinking about the differentiation here versus the many BAFF-APOL1 type of assets here. I know, obviously, it's data-dependent. I want to get your high-level comments. Thank you.

You bet. Jeff, let me ask Duncan to take the question on Aliftrack, and I'll come back for POVI.

Good afternoon, Jeff. So yes, as far as Aliftrack is concerned, I would say that the vast majority of the newly eligible patients in the U.S. have now started on Aliftrack, and we're seeing the discontinued and transition patients transition nicely over to Aliftrack as physicians are navigating the monitoring requirements over the first few months.

The patient transitions remain steady, and we're very happy with the progress. Outside the U.S., we're also seeing strong uptake in those countries with access. And I would add that in the 10 months since the launch of Alyftrek, it's generated close to $500 million of sales in revenue. So overall, we're pretty happy with the pace of progress on Alyftrek.

Jeff, on povetacicept acceptance, let me focus my comments on IGAN. It is really very exciting. The data that we're going to share at the ASN, which is this coming week, is more patients' worth of data and longer follow-up. And you should look for the endpoints of proteinuria, hematuria. You should also look for the pharmacodynamic marker in IGAN, which is called Gd-IgA1. I am very, very excited about these results.

To me, if you think about IGAN and what it means, it is a chronic disease that unfortunately results in death, dialysis, or transplantation. That's what ends up happening to our patients. And so what we're really trying to do here is get those autoantibodies under control in order to mitigate that endpoint. If you look at the disease, it's a disease of elevated APRIL levels and elevated BAFF levels. It's not the case that just one of those two cytokines is elevated. So it makes all the sense in the world to me to inhibit both, which is what POVI does. The next thing to look at is the preclinical data. And you've heard me say before, the reason we were so excited about Alpine and POVI is because it was specifically engineered for higher tissue distribution, potency, and binding affinity.

And then you translate that to the early data that we see in the clinic through Ruby 3, and it looks really good. Last thing I'll say is for patients who have this as a chronic disease, the important thing is that they have a medicine, a biologic that they can take over time that is best for them. And from all of the data, not only in market research for IGAN patients, but you look at biologics in the marketplace, it's about the dosing, small volume. It's about having an autoinjector and monthly dosing, which are key, and that's what we have with POVI. Last thing to say, I do think nephrologists are also going to be interested in the fact that we've already started our phase two, three trial in membranous. So all in all, it's pretty neat.

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

Good afternoon. Thanks for taking my question. Just to follow up on Jeff's here with the POVI data. With all those markers that we're going to look at in the longer-term phase 2 data, maybe put that in context for us about how to think about the read-through to eGFR benefit and just kind of overall positioning as we look to these other two drugs that are out there or more. And then secondly, on the pain franchise, you've talked for a bit about getting that third PBM on board prior to really opening up distribution. Could you just help us understand what's being finalized on that end? Thank you.

Yeah. Let me take the POVI question first, Salveen, and then I'll ask Duncan to comment on the last of the three PBMs.

So Salveen, in many renal diseases, including in IGAN, there is a very strong association of correlation between reduction in proteinuria and stabilization in GFR. And I expect that that will hold up in all of these phase 3 data that we see. I think the important thing to note, though, is that while the final endpoint, that's to say even for traditional approval, is GFR showing the stabilization of GFR, what we're really trying to do for our patients is to prevent those long-term complications of death, dialysis, and transplantation. It's just that the endpoint, if we measure that, would take too long. So the agency has accepted GFR slope stabilization of that as the final endpoint.

And so when you look at all of the evidence that's been generated over the course of time, the medicine that has the best reductions in proteinuria, in hematuria, in this Gd-IgA1, I think that's the medicine that's going to be best for patients if you think about the long-term outcome. But I do think that the association of proteinuria and GFR will hold, and I expect that you will see that. Duncan.

Salveen. So I think it's important to note that we're building a long-term pain franchise here where clearly we want to secure broad access for patients, but we also want to ensure long-term value of our medicines. So we feel very happy with the progress we've made so far in securing 170 million lives for Jurnavix in a relatively short period of time.

I would say that we're in productive ongoing conversations with the third PBM, and obviously, we'll keep you updated as we have news there, and as you know, in the meantime, patients who are not covered can get Jurnavix through the patient support program, so overall, we're pleased with the access progress to date. It will continue to expand over the balance of 2025 and 2026, and in the meantime, of course, a key performance indicator is continued physician uptake and prescription growth while we secure access, and on that point, although you didn't ask, I would just reference the prescription growth. We saw 10,000 prescriptions in quarter one, 90,000 prescriptions in quarter two, 170,000 prescriptions in quarter three, and of course, several thousand in October, so we're very happy with the acceleration we're seeing in prescriptions while we finalize access.

The next question will come from Jessica Fye with J.P. Morgan. Please go ahead.

Hey, guys. Good afternoon. Thanks for taking my question. I was wondering if you could just touch on what your current priorities are as it relates to capital allocation and specifically on the business development front. Is there a phase of development you feel is the sweet spot for assets that Vertex brings in? Thank you.

Yeah. Just no change in our priorities for capital allocation. We've said for some time now our top priority is to reinvest in the business, both internally and externally, to drive innovation and growth. That continues to be true. We are investing in our pipeline right now in commercialization. We are making capital investments in support of the business as well, and that remains the top priority. A secondary priority for us is share buybacks.

We were very active in the third quarter, taking advantage of the volatility in the stock price after the last earnings call. So we were out there buying aggressively in the quarter at prices that we think are quite attractive. And so that combination of reinvestment in the business as well as share buybacks will continue to be the priority going forward. In terms of whether we are looking for assets of any specific stage of development, I think you know with our sandbox approach, we are always looking for the best technology and the best assets in any of the disease areas where we are focused. That sometimes takes the form of enabling technology. Sometimes it takes the form of programs that are either preclinical or in the clinic. We were certainly very happy with the Alpine acquisition last year.

If we could find something like that again, we would certainly be interested. But we are open to all types of deals that move our strategy forward in our different disease areas.

Vertex Pharmaceuticals (VRTX) Q3 2025 Earnings Call Transcript

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