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. Third quarter performance extended our strong momentum for the year, with continued outstanding commercial execution in both CF and the early launch of CASGEVY, as well as launch preparedness for two potential near-term approvals in early 2025.
We also continue to rapidly progress programs in our clinical pipeline and achieved a significant milestone with three new programs advancing into Phase 3 clinical trials in just the last quarter. In CF, we are reaching more patients and delivered $2.77 billion in revenue, representing 12% growth this quarter versus Q3 2023. Based on the strong growth year-to-date and our Q4 outlook, we are increasing our full-year product revenue guidance to $10.8 billion to $10.9 billion, while maintaining our previous operating expense guidance.
With CASGEVY, the early launch is going very well. The enthusiasm from patients and physicians remains high and we are pleased with the ATC and patient cell collection metrics. I'm particularly pleased to share that in Q3, the first patient received commercial CASGEVY, resulting in the first revenue recognition for this medicine.
With respect to the overall pipeline, we remain on track to deliver our January 2023, five in five ambition with five new product launches over five years as we advance into this new era of revenue diversification. Specifically, in addition to the CASGEVY launches in sickle cell disease and beta thalassemia, we are preparing for potential third and fourth product launches in early 2025, the vanzacaftor triple in CF globally and suzetrigine in moderate-to-severe acute pain in the US.
Beyond that, the programs in Phase 3 development inaxaplin in APOL1-mediated kidney disease, suzetrigine in diabetic peripheral neuropathy, povetacicept in IgA nephropathy, and VX-880 in Type 1 diabetes are all progressing nicely. And we're also making strong progress in our mid-stage clinical pipeline with potentially transformative medicines VX-993 in acute and peripheral neuropathic pain, VX-670 in myotonic dystrophy type 1 or DM1 and povetacicept in indications beyond IgA nephropathy.
Tonight, I'll focus my R&D comments on CF and four additional programs that have made notable advancements this quarter. First, in CF, our four marketed medicines are treating the underlying cause of disease in more than 68,000 patients around the world. This includes children as young as one month with KALYDECO, as young as one year with ORKAMBI and as young as two years with TRIKAFTA. We are poised for the potential approval of the vanzacaftor triple, our fifth medicine for people with cystic fibrosis, six years of age and older. We have a PDUFA date of January 2 in the US and we have also completed submissions in the EU, the UK, Canada, Australia, New Zealand and Switzerland. Reviews in these jurisdictions are underway. We have also already initiated the clinical trial in children with CF ages two to five.
Finally, in CF, VX-522, our CFTR mRNA therapy in development with our partners at Moderna has completed the single ascending dose portion of the Phase 1/2 study and continues in the multiple-ascending dose or MAD portion. This therapy seeks to provide treatment for the more than 5,000 people with CF who do not make any CFTR protein and we expect to share both safety and efficacy results from the MAD in the first half of 2025.
Next, in type 1 diabetes, VX-880 is the stem-cell derived fully differentiated islet cell investigational therapy for people with type 1 diabetes and impaired hypoglycemic awareness, who experienced severe hypoglycemic events or SHEs despite optimal medical care. I am very pleased to share that we have completed our end of Phase 2 meetings with FDA, EMA and MHRA. And following the successful regulatory interactions, we have reached agreement with regulators to advance the current Phase 1/2 VX-880 study to pivotal development and convert the trial into a Phase 1/2/3 study. This trial will include a total of 50 patients with difficult-to-control diabetes and severe hypoglycemic events despite optimal medical management.
In this Phase 1/2/3 study, the primary endpoint is the proportion of patients achieving insulin independence with the absence of severe hypoglycemic events. We are excited to be in pivotal development for this groundbreaking potentially curative therapy for patients suffering from the most severe form of type 1 diabetes. It is particularly noteworthy that the first ever pivotal trial of an allogeneic regenerative cell therapy for type 1 diabetes is beginning less than a year-after we received the first-ever approval for CRISPR/Cas9 gene-edited cell therapy with CASGEVY. We are proud of the progress represented by these advancements in the cell and gene therapy space.
To close-out on the VX-880 program, I'll provide a quick recap on the data presented at EASD this September. These remarkable data form the basis of our recent regulatory discussions and included more patients with longer duration of follow-up compared to the ADA presentation. These data showed four patients had 12 months of follow-up and all four achieved the primary and secondary endpoints. Specifically, they had elimination of severe hypoglycemic events, achieved insulin independence and achieved the ADA recommended hemoglobin A1c levels of less than 7%. Also at EASD, we shared that an additional five patients were off exogenous insulin as they progressed toward the 12-month primary endpoint evaluation. Safety and tolerability with this latest data cut were consistent with the June ADA presentation.
Beyond VX-880, our [Indecipherable] device or VX-264 program encapsulates the same VX-880 cells in a proprietary device designed to eliminate the need for immunosuppressants. We are currently enrolling and dosing patients in Part B, which is at the full target dose with the stagger between patients. The next stage Part C of the trial is at the full target dose without a stagger. We expect to share data from Parts A and B of the VX-264 study in 2025.
Moving now to the povetacicept program. Pove is a dual antagonist of the BAFF and APRIL 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 pove's once monthly dosing frequency with small volume subcutaneous route of administration give us high confidence in the promise of povetacicept as a transformative medicine for patients with IgA nephropathy and potentially additional B cell-mediated diseases.
Pove recently hit multiple milestones. First, I'm very pleased to share that we began the global Phase 3 RAINIER study of pove in patients with IgA nephropathy. The study is a randomized double-blind trial of pove 80 milligrams versus placebo on top of standard of care. The trial is underway with screening, enrollment and dosing ongoing across multiple clinical sites globally. Importantly, the trial is designed with a pre-planned interim analysis to evaluate proteinuria when a certain number of patients reach the 36-week time point. This pre-planned interim analysis could support a potential accelerated approval in the US. For full approval, the study will continue through week 104 and assess GFR.
Second, the recently initiated RAINIER Phase 3 study was supported by positive data that we shared at the recent American Society of Nephrology Meeting. In IgA nephropathy, updated Phase 2 data on patients with IgA nephropathy who received 80 milligrams of povetacicept continue to demonstrate pove's best-in-class potential with a mean 66% reduction from baseline in UPCR at 48 weeks with stable renal function. These results were accompanied by a 63% achievement or five out of the eight study participants of clinical remission, defined as UPCR of less than 0.5 grams per gram negative hematuria and stable renal function. We are very excited about these results and the potential they represent for IgAN patients globally, including the approximately 130,000 patients diagnosed in the US.
Third, at ASN, we shared emerging pove data from another renal B cell mediated disease, primary membranous nephropathy, a disease that affects 60,000 patients in the US with no approved targeted therapies. These data are from three patients who receive pove at 80 milligrams subcutaneously every four weeks. On proteinuria, at 24 weeks, treatment with pove resulted in a mean 62% reduction from baseline in UPCR and two of the three patients achieved partial clinical remission defined as UPCR of less than 3.5 grams per gram and greater than 50% reduction in UPCR from baseline. In addition, anti-PLA2R antibodies, a biomarker of disease activity declined by a mean of 87% at week 20 in these patients.
Across the renal studies, pove was well-tolerated and most adverse events were mild or moderate. We look forward to updating you as the pove programs progress.
Shifting gears now from pove to the pain portfolio and starting with acute pain. The FDA review of suzetrigine in moderate-to-severe acute pain is well underway with the PDUFA date of January 30, 2025. The Phase 3 data from the two RCTs and the single-arm safety and effectiveness trial that formed the basis of the acute pain regulatory submission were presented for the first time at the recent American Society of Anesthesiology Annual Meeting. There was very strong physician interest and positive feedback to the presentation of this data set and we now look-forward to the completion of the regulatory review, potential approval and launch of suzetrigine. Stuart will provide more detail on the acute pain launch readiness.
As suzetrigine progresses through its regulatory review, additional assets in the pain portfolio are also advancing through clinical development. Our next generation NaV1.8 inhibitor VX-993 is being studied in two acute pain studies, a Phase 2 study post bunionectomy with the oral formulation and a Phase 1 study with the IV formulation. We also continue to make strong preclinical progress with our NaV1.7 pain signal inhibitor program that may be used alone or in combination with NaV1.8 inhibitors.
In peripheral neuropathic pain or PNP, in diabetic peripheral neuropathic pain, which is one type of PNP for which an estimated 2 million Americans seek a prescription pain medicine annually, I am very pleased to share two updates. First, we have initiated the Phase 3 pivotal program for suzetrigine. Second, we have also initiated a Phase 2 study with the oral formulation of VX-993.
And in lumbosacral radiculopathy or LSR, another type of PNP that impacts more than 4 million Americans each year and for which there are no specifically approved medicines in the US, we have completed the Phase 2 trial. We remain on track to share Phase 2 results from this study by the end of this year. As a reminder, this is a 12-week trial of about 200 patients randomized to either suzetrigine 69 milligrams or placebo. The primary endpoint is the within group change in the NPRS score from baseline to the end-of-the 12-week study. The design allows for an efficient evaluation of the magnitude of the treatment effect for suzetrigine as well as the placebo group, so that we may appropriately size a potential Phase 3 trial if the Phase 2 data support advancement.
To wrap-up the discussion on the pipeline today, a brief update on the myotonic Dystrophy Type 1 or DM1 program. DM1 is the most prevalent type of muscular dystrophy impacting 110,000 patients in the US and Europe and for which there are no approved therapies. Our Phase 1/2 clinical study of VX-670 initiated late last year and I am pleased to share that the program has accelerated. The SAD portion of the Phase 1/2 clinical trial has completed dosing and we have initiated the MAD portion of the study.
In the MAD, we will be collecting both safety and efficacy data. The primary endpoint is safety and the secondary endpoint is the change from baseline in the splicing index on muscle biopsy. We are excited about the progress and potential for VX-670 and look forward to providing updates on this program as it advances.
With that review of the R&D highlights, I'll now turn it over to Stuart for a commercial update.
