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

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Culture rank

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Best Workplaces For Women

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Best Companies

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Compressed work weeks

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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

CEO/Top executive

Group headquarters

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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

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Good day, and welcome to the Vertex Pharmaceuticals Fourth Quarter twenty twenty four Earnings Call. All participants will be in a listen only mode. 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.

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 fourth quarter twenty twenty four financial results conference call. On tonight's call making prepared remarks, we have Doctor. Reshma Kewal Rahmani, Vertex's CEO and President Stewart Arbuckle, Chief Operating Officer and Charlie Wagner, Chief 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.

Thanks, Susie. Good evening, all, and thank you for joining us on the call today. Before diving into Q4 and full year earnings, I'd like to provide a quick update on some leadership changes planned for mid-twenty twenty five, as noted in our press release. Stuart Arbuckle will be retiring on July one of this year after an almost forty year career in biopharma and a stellar dozen plus years at Vertex, first as Chief Commercial Officer and then as COO. Stewart reimagined the Vertex Commercial Organization as the company transitioned from hepatitis C and in CVIC to establishing itself in CF.

And since then, he has led as Vertex's Chief Commercial Officer and Chief Operating Officer with great skill and innovation. Stuart has been at the helm through the launches and commercialization of all of our CFTR modulators, beginning with Kalydeco and all the way through to a Lyft track. He has also helped develop and lead the organization into this new era of commercial diversification with the launches of Kasevy and Journavix. Anyone who has had the privilege to work with Stuart, as I have, knows Stuart to be a consummate professional, an incredible leader, and an excellent developer of talent. He's uncommonly poised, leads with integrity, and always puts patients first.

As part of our carefully planned succession, Stewart is fully on board at Vertex until July, which will allow for a seamless transition. While we still have many months before he retires, I want to take this opportunity to convey my deep gratitude for his partnership and for all that Stewart has done for Vertex. We are very thoughtful and deliberate in how we plan for senior leader succession, and we always do so with a long time horizon in mind. Thanks to this careful planning, we have never been in a stronger position to pass the baton from Stuart to other experienced senior leaders, and we are very confident that the transition will enable us to execute seamlessly on the significant opportunities ahead. In that regard, I am very pleased to announce that Charlie Wagner, who joined as CFO in April of twenty nineteen and whom all of you know very well, will take on the additional role of COO on July 1.

I am equally pleased to announce that Duncan McKechnie, our longtime SVP and Head of the North American Commercial Team will be promoted to EVP and Chief Commercial Officer also on July 1. Duncan had over twenty years experience in the industry across a wide range of strategic, operational and commercial roles in multiple disease areas and geographies at both GSK and Novartis prior to joining Vertex twelve years ago. Duncan has been working side by side with Stuart since 2013, during which time he played an instrumental role architecting the successful launches of all of our CF medicines, as well as the KASCEV and Genomics launches in The U. S. In addition to his role as the commercial head of North America since 2022, Duncan has also led the global health economics, as well as the global value and access functions across the entire Vertex portfolio.

I'm proud of the deep bench of outstanding talent we have at Vertex, and I'm looking forward to working directly with Duncan as he joins the executive committee and steps into the CCO role, and as Charlie continues as CFO and adds COO responsibilities in July. Moving to earnings, fourth quarter performance wrapped up another strong year as the continued outstanding commercial execution in CF helped us drive double digit revenue growth for our tenth consecutive year and the launch of Kast Jebi set us on the course of revenue diversification. We continue to reach more patients and deliver $2,910,000,000 in revenue in the fourth quarter, representing 16% growth versus Q4 twenty twenty three. For the full year 2024, revenue reached a new milestone of just over $11,000,000,000 plus 12% versus 2023 and exceeded our full year product revenue guidance of $10,800,000,000 to $10,900,000,000 From the strong base in 2025, we are focused on driving a significant expansion in the patients we serve with the ongoing launch of KASGEBI and two recent US NDA approvals. Aliftrec, our next generation fifth CF medicine approved on December 20, and Journavix approved for moderate to severe QPain on January 30.

The Journavix approval is landmark as it represents the first oral non opioid pain signal inhibitor and the first new class of pain medicine in over twenty years. We see this approval as significant for millions of patients, for Vertex, and for society as an important option to support public health efforts to curb the opioid epidemic. Our R and D teams have worked on this program for many years, and it is indeed my privilege to acknowledge their efforts and also to thank the patients and healthcare providers who participated in the clinical trials and made this approval possible. With these two recent approvals for Liftrec and Journavix in hand and the continuing KASCEV global launch, we have a keen focus on commercialization and our teams are working to secure broad access and reimbursement for patients who are waiting. As I detailed in January, as the number of in line approved medicines grow and the late stage pipeline advances, we anticipate significantly expanding the number of patients we serve over the coming years.

In 2024, our transformative therapies have the potential to serve approximately one hundred and sixty thousand patients with CF, sickle cell disease, and transfusion dependent beta thalassemia. Now we can add eighty million acute pain patients to that reach, thanks to the approval of Genabix. And beyond moderate to severe acute pain, focusing just on the mid and late stage pipeline, we seek to serve more than five million more patients, including those with type one diabetes and certain renal diseases, and then another ten million plus patients with peripheral neuropathic pain in The U. S. Alone.

To give you a sense of our momentum, we are on track for key clinical development milestones in three pivotal studies this year. First, completing enrollment and dosing in the Zimylacel phase one, two, three study in type one diabetes, which would position us to file for regulatory approval once this cohort has follow-up with one year of insulin independence. Second, completing enrollment in the interim analysis cohort of popitastacept in IgAN, which would position us to file for potential US accelerated approval once that cohort reaches thirty six weeks of treatment. And third, completing enrollment in the interim analysis cohort for enaxopline for AMKD, which would position us to file for potential U. S.

Accelerated approval once that cohort reaches forty eight weeks of treatment. In addition, we continue to execute the phase three study of succetri gene in patients with diabetic peripheral neuropathy. We're also making strong progress with VX993, the next generation NAV one point eight inhibitor, in both moderate to severe acute pain and diabetic peripheral neuropathy. We also have ongoing trials of potentially transformative medicines like VX-six seventy in myotonic dystrophy type one, popatacept in a basket study in indications beyond IgAN, and expect to move VX-four zero seven for autosomal dominant polycystic kidney disease into phase two this summer. It's truly an exciting era of broad diversification at Vertex in terms of the revenue base, our pipeline and our geographic presence.

Given the detailed clinical update we provided in January, I'll focus the R and D updates tonight on CF and our clinical stage renal pipeline. Starting with CF, the U. S. Launch is underway for a lift track, the fifth vertex CFTR modulator regimen, while we are also working to secure approval in international regions. As we work to get a lift truck to patients around the globe, we are already in the clinic with our next generation CFTR modulator regimen.

With each CFTR modulator regimen that gains approval, we raise the bar ever higher for ourselves and the field as a whole as we continue our mission to bring all patients with CF to normal levels of CFTR function. We term Trikafta, CAFtrio, the next generation CFTR modulator or NG one point zero. A left track is NG two point zero. The NG three point zero regimen consists of VX828, a CFTR corrector, VX118, a CFTR potentiator, and tezacaftor. This NG three point zero triple combo regimen has shown even greater efficacy.

In other words, even greater improvement in CFTR dependent chloride transport than in LifTReq in our CF human bronchial epithelial cell assays, which have been shown to be highly predictive of clinical outcomes. We expect this regimen to be in the clinic in a study of CF patients this year. We also continue to enroll and dose the MAD portion of the phase onetwo study of VX five twenty two for the 5,000 plus patients who cannot benefit from our CFTR modulators. Results from the MAD portion of the study are expected later this year. Moving on now to what I see as a real renaissance in renal therapeutic drug development.

We are focused on advancing potential therapeutics that hold a promise to treat the underlying cause of disease in three different severe renal conditions. First, enaxiply for APOL1 mediated kidney disease or AMKD. As mentioned, we are working towards our goal of completing enrollment of the interim analysis cohort of the pivotal AMPLITUDE study this year. AMPLITUDE is a study of primary AMKD. That is to say patients with two APOL1 alleles and no additional renal comorbidities.

After completing enrollment, when this cohort reaches forty eight weeks of treatment, we'll conduct the interim analysis. If positive, we will be able to file for potential accelerated approval in The US. In addition, I'm pleased to announce that last month we initiated a new study, AMPLIFIED, which is a phase two proof of concept study of enaxoplin in patients with AMKD and other comorbidities, including type two diabetes. Second, povatastacept, a dual antagonist of the APRIL and BAF cytokines, which play key roles in the pathogenesis of B cell mediated autoimmune diseases. This stool inhibition mechanism of action, the preclinical and clinical data to date, plus po v's once monthly dosing frequency and small volume subcutaneous route of administration give us high confidence in its promise as a transformative medicine for patients with IgAN and other B cell mediated diseases.

As mentioned in January, we expect to complete enrollment of the interim analysis cohort of the Povis study in IgAN this year. To this end, I am pleased to report that we have now opened more than 100 clinical trial sites in more than 20 countries, including in The US, Europe, and Asia, and enrollment and dosing are well underway. Once this cohort has thirty six weeks of follow-up, we'll conduct the interim analysis. And if positive, it would support filing for a potential accelerated approval in The US. And third, an earlier stage renal program that represents an additional significant opportunity, VX401 in autosomal dominant polycystic kidney disease or ADPKD, where we are nearing completion of the phase one trial.

ADPKD is the most common severe monogenic disease amongst Caucasians, and the most common inherited cause of end stage renal disease in The US and globally. An estimated three hundred thousand people in The US and Europe are living with ADPKD, yet there are no treatments that address the underlying cause of disease. It is a life shortening disease that is characterized by the growth of numerous cysts that impair kidney function and can ultimately lead to kidney failure. Around half of patients with ADPKD experienced kidney failure by the age of 60. The majority of ADPKD cases are caused by variants in the PKD one gene, which encodes the polycysteine one or PC1 protein.

These inherited variants lead to the loss of PC1 function that leads to the proliferation of kidney epithelial cells, increased fluid secretion, and the formation and expansion of fluid filled cysts. The progressive cyst formation causes an increase in kidney size and decline in kidney function. VX four zero seven is a first in class small molecule protein folding corrector that is designed to target the underlying cause of ADPKD by correcting PC1 folding to restore function. This has the potential to arrest cyst growth. By way of its mechanism of action, VX-four zero seven has potential in a subset of patients with protein folding mutations of PKD1, estimated at up to thirty thousand patients or about ten percent of the overall ADPKD population.

As we're doing in CF, we seek to serially innovate, and over time reach the full three hundred thousand patients with ADPKD. For VX four zero seven, we expect to complete our phase one study soon. And if the results are supportive, advance to phase two later this year. With that review, I'll turn it over to Stuart for a commercial update.

Thank you very much, Reshma. While I admit to having very mixed emotions at retiring from Vertex in July, I know that the timing is right from both a professional and personal standpoint. It's been an amazing journey at Vertex over the last thirteen years as we've executed in our unique and differentiated strategy to develop and commercialize transformative medicines for patients with CF, sickle cell disease, beta thalassemia and pain. And I'm very confident we will successfully develop many more transformative medicines such as in diabetes, renal and autoimmune diseases from our broad late stage clinical pipeline. The business has never been in a better position scientifically and commercially than we are today.

I'm also highly confident that we have developed the right talent to maximize these significant opportunities. I'm thrilled to transition leadership of our outstanding commercial organization to Duncan as the new CCO. I've known Duncan for decades and recruited him to Vertex. He brings a rare combination of outstanding strategic thinking, results focused operational excellence and people management skills, and I have every confidence he will help lead the company to even greater heights. Although I will see many of you between now and July, I'd like to take this opportunity to thank all our shareholders and analysts for your support and engagement over the years, And I look forward to helping you get to know Duncan over the coming months.

With that, I will focus my comments tonight on our three recent launches, including the early U. S. Launch of a lift truck, the continuing global launch of Kaschevy building on the foundation we established in 2024 and the initial launch of Jonavix in acute pain. Starting with CF. Once again, we delivered strong CF results for the quarter and the full year as we further grew the number of eligible patients taking our CFTR modulators.

We made rapid regulatory and reimbursement progress in 2024, enabling us to expand to younger patients, patients with rare mutations and patients in new geographies. Aliftrec is now our fifth CFTR modulator approved to treat the underlying cause of CF. We were pleased with the early approval of Aliftrec, which in clinical trials has demonstrated non inferiority on lung function to Trikafta, the current standard of care for eligible patients with CF. Aliftrec clinical trials also demonstrated further improvements in CFTR function as measured by sweat chloride. We believe this profile along with the convenience of once daily dosing sets the stage for Aliftrec potentially become the new standard of care in CF.

Aliftrec is also approved for an additional thirty one mutations that are not covered by the Trikafta label. And finally, Aliftrec carries a meaningfully lower royalty burden for Vertex and extends our composition of matter patent protection from 02/1937 for Trikafta into 02/1939 for Aliftrec. We have received positive feedback from physicians and patients for Aliftrec. Early insights show enthusiasm for a new option that offers the convenience of once daily dosing to simplify treatment and expanded eligibility for many patients who are today not being treated with a CFTR modulator, including those who have one of the 31 rare mutations that are not responsive to our other CFTR modulators. In these early days of the launch, centers are familiarizing themselves with the data and the liver monitoring requirements to frame conversations about initiation with naive, discontinued and potential SWIT patients.

We have seen interest in a lift track from all of these groups of eligible patients. And I'm pleased to report that the first patients have already initiated treatment with a lift track. As we think about the uptake of a Liftrec, we are confident that CF patients will seek the best medicine for them. And we believe that for the majority of patients, that is a Liftrec. We expect that the short term liver monitoring requirements to initiate a Liftrec will be considered in the context of the potential for a lifetime of improved CFTR function and the benefits of once daily dosing.

Outside The U. S, regulatory reviews are underway for a lift track, including in The United Kingdom, European Union, Canada, Switzerland, Australia and New Zealand. We look forward to the potential approvals of this best in class medicine in these markets in 2025. Now turning to KASCEV, our transformative one time treatment for patients with sickle cell disease and beta thalassemia. It is just over a year since the historic approval of KASCEV, which has been enthusiastically received by patients, physicians, payers and policymakers and the launch is gathering momentum across all regions.

Two important markers of our launch progress are ATC activations and patient cell collections. As we reported in January, we exited 2024 with more than 50 authorized treatment centers, well on our way to our goal to activate approximately 75 total ATCs globally. Approximately 50 patients across all regions have their first cell collections in 2024 and patient infusions of KASGEWI edited cells have already occurred in both The Middle East and The U. S. We continue to make exciting progress in The Middle East.

In November of twenty twenty three and January of twenty twenty four, we secured regulatory approvals in Bahrain and KSA respectively. And on 12/31/2024, we secured regulatory approval in The United Arab Emirates. We are working to expand further in the region with anticipated filings in Kuwait and Qatar later this year. In this region, we now have national reimbursement in Bahrain, hospital based coverage in Saudi Arabia, and are working towards coverage in The United Arab Emirates. Continuing with the payer landscape, we recently reached a reimbursement agreement with NHS England for the treatment of patients with sickle cell disease.

This means that eligible sickle cell disease and beta thalassemia patients now have access to KASCEV in England. In The US, both SCD and TDT patients have access either through private insurance, where over two fifty million lives are covered, or through single case agreements. And in the Medicaid segment, as of last month, states may now begin to apply to participate in the CMMI cell and gene therapy access model, which we believe will further expand access for eligible patients as states may then subsequently opt in to the CMS negotiated agreements. We are focused on leveraging the foundation we established for Kastyaevi in 2024 to build momentum in 2025 and beyond for this multibillion dollar opportunity as we work to get this transformative therapy to more and more patients around the world. Shifting now to Genavix in acute pain as we are currently ten days post the milestone approval of this first selective oral non opioid pain signal inhibitor.

The approval is so critical because Genavix represents the first new class of pain medicine in over twenty years. It combines effective pain relief with a favorable safety profile and based on its MOA, it does not have addiction potential. It is indicated for use across all types of moderate to severe acute pain. For example, post surgery, broken bones, sports injuries, and has the potential to establish a new standard of care for the eighty million patients who seek a prescription therapy to treat moderate severe acute pain each year in The US. Half of those seeking help for their acute pain or approximately forty million Americans each year are prescribed opioids, which although effective, have significant safety and tolerability concerns and addictive potential.

In fact, tragically, an estimated eighty five thousand people each year will develop opioid use disorder within the first year of being prescribed an opioid for acute pain. We believe we now have the opportunity to transform how acute pain is treated in The U. S. And to build another multi billion dollar franchise for Vertex. We were launch ready for the PDUFA date and have now begun commercialization of Genavix.

Our focus for 2025 is to engage with healthcare professionals, formulary decision makers and payers to establish the conditions for rapid patient access that will deliver long term commercial success for our pain franchise. To that end, while still just a few days into the launch, we believe that the incredibly broad positive media coverage JONAVICS has received since approval is one measure of the high unmet need and an indication of the societal importance of providing both physicians and patients with a new non opioid option for the treatment of acute pain. We've already seen tremendous interest and requests for information from both doctors and patients, and we look forward to being able to serve them. Our 150 person sales force is actively engaging with healthcare providers and physicians on the compelling efficacy and safety data of generics and its role in all types of moderate to severe acute pain. In the institutional setting, we are engaging with roughly 2,000 high volume hospitals and approximately 150 related health systems.

We have line of sight to accelerate the typical P and T committee processes in many network to support the use of generics in this setting. We are advancing our discussions with national and regional payers and group purchasing organizations to provide access to generics, building on our work preapproval to accelerate formula reviews and limit inappropriate utilization management controls. And lastly, with retail pharmacies, we are working to secure broad stocking agreements at national retail pharmacies and regional chains to ensure availability of genomics for patients across the country. We have also now begun our non personal promotional initiatives to physicians and patients to promote broad awareness of the first oral non opioid pain signal inhibitor for moderate to severe acute pain, such as embedded content in relevant websites like Medscape for Physicians and WebMD for Consumers, along with point of care marketing. Furthermore, we continue to see momentum and interest by policymakers, both on the federal and the state level in providing equal access to non opioid options for pain relief.

The No Pain Act launched on January and provides a Medicare add on payment for non opioids used in the hospital outpatient or ambulatory surgery center settings. We expect JONAVICS to be added near term to the list of medicines approved for this add on payment. The Alternatives to Pain Act had 78 cosponsors from both parties last year and is expected to be reintroduced in the new Congress with similar and growing support. Additional federal and state initiatives also continue to progress. For example, just six weeks into 2025, '17 states have already introduced legislation to support the use of non opioid options, adding to the seven states that enacted legislation for Medicaid and state regulated plans in 2024.

We expect more states to join this movement. On the pricing front, we have priced Genavix at $15.5 per pill or $31 per day at list price. We believe this price strikes a balance between ensuring broad access with the benefits it brings to patients and society, including the cost offsets that Genavix may provide. It also recognizes our twenty plus year investment in pain. And significantly, we feel that this pricing enables us to continue to invest so that we can be the leader in serving patients with acute and chronic pain for decades to come.

As previously discussed, in the early months of the launch, we are strategically investing in initiatives, including financial assistance programs for eligible patients that enable smooth, rapid access for patient prescribed genomics, which is critical given the acute nature of the condition. And lastly, we expect to start shipping GenaVix to wholesalers by the end of this month with retail availability a few days later. To conclude, we had a very strong commercial execution throughout 2024 and are already executing on the multiple launches and growth opportunities ahead of us in 2025. We are in a new and exciting era of commercial diversification with the ongoing global launch of Kashchevy, the launch of a lift track in CF and JONAVICS in moderate to severe acute pain in The U. S.

I'll now turn the call over to Charlie to review the financials.

Thanks, Stewart. Vertex's excellent results in the fourth quarter of twenty twenty four demonstrate once again our consistent strong performance and attractive growth profile. Fourth quarter twenty twenty four total product revenue increased 16% year over year to $2,910,000,000 including revenue growth of 17% in The U. S. And 14% outside The U.

S. The exceptional U. S. CF revenue growth in the quarter resulted from continued strong patient demand and the effect of the January 2024 price increase as well as a favorable gross to net dynamic. Ex U.

S. Revenue growth was driven by strong CF performance in many established markets as well as in newer markets where we have recently transitioned to long term reimbursement agreements. Revenue in the quarter also benefited from certain non recurring items. Full year revenue of $11,020,000,000 represents 12% growth versus 2023, our tenth consecutive year of double digit growth. Fourth quarter twenty twenty four combined non GAAP R and D acquired IP R and D and SG and A expenses were $1,300,000,000 an increase of 29% compared to $1,000,000,000 in the fourth quarter of twenty twenty three.

The most significant areas of increased investment versus prior year included the pivotal studies for Type one diabetes, IgAN, AMKD and DPN, as well as the build out of capabilities for both our expanding pipeline and ongoing commercial launches. Also included in Q4 twenty twenty four results are $88,000,000 of acquired IPR and D expenses, including for the Orna collaboration to develop next generation in vivo therapeutics for sickle cell disease and beta thalassemia. This compares to $18,000,000 of such charges in the fourth quarter of twenty twenty three. Full year 2024 combined non GAAP R and D, acquired IPR and D and SG and A expenses were $8,820,000,000 compared to $4,240,000,000 in 2023. Included in full year 2024 results are $4,630,000,000 of acquired IPR and D charges with the vast majority resulting from the Alpine Immune Sciences acquisition.

Acquired IP R and D charges were $527,000,000 for the full year 2023. The year over year increase in R and D expenses was driven by continued investment in our pipeline, including four ongoing pivotal studies. The year over year increase in SG and A costs was primarily driven by investments in our commercial organization to support the launches of Jernavix and KAS Jevi. Fourth quarter twenty twenty four non GAAP operating income was $1,200,000,000 compared to $1,150,000,000 in non GAAP operating income in the fourth quarter of twenty twenty three. Full year 2024 non GAAP operating income was $696,000,000 compared to $4,370,000,000 in 2023.

Recall that full year 2024 non GAAP operating income reflects a 4,400,000,000 charge for acquired IPR and D from the acquisition of Alpine. Fourth quarter twenty twenty four non GAAP effective tax rate of 21.3% was in line with our expectations, while our 16.3% tax rate in Q4 'twenty three benefited from higher U. S. R and D tax credits. Our full year 2024 effective tax rate of 91% reflects the nondeductibility of the Alpine acquired IPR and D charge.

Our non GAAP effective tax rate in 2023 was 19.4%. Fourth quarter twenty twenty four non GAAP earnings per share were $3.98 compared to $4.2 in the fourth quarter of twenty twenty three, largely as a result of lower interest income and the tax rate differential previously noted. Full year 2024 non GAAP earnings per share were $0.42 compared to $15.23

and D charge equates to roughly zero point priorities for cash deployment remain unchanged as we continue to prioritize investment in innovation, including external innovation via business development. We also continued our share repurchase program and deployed approximately $1,200,000,000 to repurchase 2,700,000.0 shares over the course of 2024, including 961,000 shares in the fourth quarter. Now switching to guidance. For 2025, we expect total revenue in a range of $11,750,000,000 to $12,000,000,000 representing growth of approximately 8% at the midpoint at current exchange rates with The U. S.

As the main driver of total revenue growth. This outlook reflects our expectation for continued growth from our portfolio of CF medicines, including The U. S. Launch of Aliftrec. Note that ex U.

S. CF revenue growth will be impacted by a reduction of revenue in one country outside our core markets where certain intellectual property rights are being violated. This impact will be most pronounced in Q1 as the increases in international channel inventory that occurred in Q1 of twenty twenty four will not repeat in Q1 twenty twenty five. Guidance also includes a continued ramp up in KASCEV revenue as we treat more patients in approved geographies. Given the very recent approval of Jynavix, guidance also reflects a contribution from this launch in The U.

S. Primarily in the back half of the year. We expect Jernavix volumes to ramp up ahead of revenue as a result of financial assistance programs that are designed to provide eligible patients with immediate access while we work to secure broad sustainable payer coverage. To give you context on the launch progress of Jernavix, we will provide metrics on total covered lives and prescription data over the course of 2025. Also note that the expected benefit to lift track will largely be offset by the higher cost of goods on our other new product launches as they scale towards their long term margins.

For combined non GAAP R and D, acquired IP R and D expenses and SG and A, we project a range of $4,900,000,000 to $5,000,000,000 for the full year 2025. This guidance includes approximately $100,000,000 in currently anticipated IP R and D charges. We will continue to invest a majority of our operating expenses into R and D given the momentum in our multiple mid and late stage clinical development programs. The cost for four Phase III studies were a driver of increased investment in Q4 twenty twenty four and this trend will continue over the course of 2025 with the four Phase three studies continuing and multiple Phase 2s ongoing as well. The increase in commercial costs in 2025 supports our increasingly diversified commercial portfolio and reflects a full year of investments to support the launch of Dernavix as well as targeted spending on commercial capabilities for future potential multibillion dollar opportunities in renal therapies and Zomyelocel, for example.

Given our differentiated business model and focus on specialty markets, we can make these targeted investments while maintaining attractive profitability and cash flow. Our full year 2025 non GAAP effective tax rate is expected to be in the range of 20.5% to 21.5%. In closing, Vertex delivered excellent results yet again in 2024, achieving strong revenue growth, advancing our Kast Jebi launch and gaining important regulatory approvals that position us for commercial launches, all while continuing to make significant pipeline progress across the portfolio. We are now launching two new products in The U. S, driving the KASCEV global launch and enrolling four Phase three studies, with three of them expected to reach significant enrollment milestones this year.

These and other anticipated milestones of continued progress in multiple disease areas are detailed on Slide 16. We look forward to updating you on our progress on future calls and I'll now ask Susie to begin the Q and A period.

We will now begin the question and answer session. And our first question will come from Salveen Richter with Goldman Sachs. Please go ahead.

Good afternoon. Thanks for taking my questions. On Jornevax and actually Stuart, we really are going to miss you and Duncan welcome here. Maybe just going back to my question on Jornevax, can you further elaborate on pre launch efforts in the retail pharmacies and the P and T Committee review processes and how you can work to accelerate these aspects? And then secondly, on your mRNA program in cystic fibrosis, maybe frame for us how you think of success here?

Vertex Pharmaceuticals (VRTX) Q4 2024 Earnings Call Transcript

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