Reshma Kewalramani
Chief Executive Officer and President at Vertex Pharmaceuticals
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-2025, as noted in our press release. Stuart Arbuckle will be retiring on July 1 of this year-after an almost 40-year career in biopharma and a stellar dozen-plus years at Vertex, first as Chief Commercial Officer and then as COO. Stuart 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 Kaleidico and all the way through to. He has also helped develop and lead the organization into this new era of commercial diversification with the launches of and. Anyone who has had the privilege to work with Stewart, as I have, knows Stewart to be a consummate professional, an incredible leader and an excellent developer of talent. He is 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 Stuart 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 Stewart 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 the CFO in April of 2019 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, 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 20 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 12 years ago. Duncan has been working side-by-side with Stewart since 2013, during which time he played an instrumental role architecting the successful launches of all of our CF medicines as well as the and Gernamics launches in the US. 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. 4th-quarter performance wrapped up another strong year as the continued outstanding commercial execution in CF helped us drive double-digit revenue growth for our 10th consecutive year and the launch of set us on the course of revenue diversification. We continue to reach more patients and delivered $2.91 billion in revenue in the 4th-quarter, representing 16% growth versus Q4 2023. For the full-year 2024, revenue reached a new milestone of just over $11 billion, plus 12% versus 2023 and exceeded our full-year product revenue guidance of $10.8 billion to $10.9 billion.
From this strong base in 2025, we are focused on driving a significant expansion in the patients we serve with the ongoing launch of and two recent US NDA approvals,, our next-generation fifth CF medicine approved on December 20th and Genavix approved for moderate-to-severe acute pain on January 30th. The approval is landmark as it represents the first oral non-opioid pain signal inhibitor and the first new class of pain medicine in over 20 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&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 Liftrek and Genavix in-hand and the continuing 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 160,000 patients with CF, sickle cell disease and transfusion-dependent beta-thalassemia.
Now we can add 80 million acute pain patients to that reach, thanks to the approval of Gernabix. And beyond moderate-to-severe acute pain, focusing just on the mid and late-stage pipeline, we seek to serve more than 5 million more patients, including those with type 1 diabetes and certain renal diseases and then another 10 million-plus patients with peripheral neuropathic pain in the US 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 cell Phase 1/2/3 study in Type 1 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 in IgAN, which would position us to file for potential US accelerated approval once that cohort reaches 36 weeks of treatment. And third, completing enrollment in the interim analysis cohort for for AMKD, which would position us to file for potential US accelerated approval once that cohort reaches 48 weeks of treatment. In addition, we continue to execute the Phase-3 study of gene in-patients with diabetic peripheral neuropathy. We're also making strong progress with VX993, the next-generation NAV1.8 inhibitor in both moderate-to-severe acute pain and diabetic peripheral neuropathy.
We also have ongoing trials of potentially transformative medicines like VX670 in myotonic dystrophy type 1, in a basket study in indications beyond IgAN and expect to move VX-407 for autosomal dominant polycystic kidney disease into Phase-2 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&D updates tonight on CF and our clinical-stage renal pipeline. Starting with CF, the US launch is underway for, the fifth Vertex CFTR modulator regimen, while we are also working to secure approval in international regions. As we work to get 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 raised 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 1.0. The left trek is NG 2.0. The NG NG3.0 regimen consists of VX-828, a CFTR corrector, VX-118 is CFTR potentiator and tezacaftor. This NG3.0 triple combo regimen has shown even greater efficacy, in other words, even greater improvement in CFTR dependent chloride transport than in Liftrek 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 1/2 study of VX-522 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, for APO1 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. 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 48 weeks of treatment, treatment will 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-2 proof-of-concept study of in-patients with AMKD and other comorbidities, including type-2 diabetes. Second, povitacept, a dual antagonist of the April and BAF cytokines, which play key roles in the pathogenesis of B-cell-mediated autoimmune diseases. This dual inhibition mechanism-of-action, the preclinical and clinical data to date, plus POVI'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 POVI 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 36 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, VX-407 in autosomal dominant polycystic kidney disease or ADPKD, where we are nearing completion of the Phase-1 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 300,000 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 experience kidney failure by the age of 60. The majority of ADPKD cases are caused by variance in the PKD1 gene, which encodes the polycystine 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-407 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 growth. By way of its mechanism-of-action, VX-407 has potential in a subset of patients with protein folding mutations of PKD1, estimated at up to 30,000 patients or about 10% of the overall AD/PKD population. As we're doing in CF, we seek to serially innovate and over-time reach the full 300,000 patients with ADPKD. For VX-407, we expect to complete our Phase-1 study soon. And if the results are supportive, advance to Phase-2 later this year.
With that review, I'll turn it over to Stuart for a commercial update.
