Vertex Pharmaceuticals is making significant strides in its clinical pipeline, with multiple programs advancing into Phase 3 trials and positive data readouts across various therapeutic areas. The company's third-quarter performance reflects strong momentum, driven by continued growth in cystic fibrosis (CF) and the early launch of CASGEVY for sickle cell disease and beta-thalassemia. Vertex is also preparing for potential near-term approvals in early 2025, including the vanzacaftor triple in CF and suzetrigine in moderate to severe acute pain.
Cystic Fibrosis
Vertex's four marketed medicines are currently treating the underlying cause of CF in more than 68,000 patients worldwide. The company is poised for potential approval of the vanzacaftor triple, its fifth medicine for people with CF ages six years and older, with a PDUFA date of January 2 in the U.S. Submissions have also been completed in the EU, the U.K., Canada, Australia, New Zealand, and Switzerland.
VX-522, Vertex's CFTR mRNA therapy in development with Moderna, has completed the single ascending dose portion of the Phase 1/2 study and continues in the multiple ascending dose portion. This therapy seeks to provide treatment for the more than 5,000 people with CF who do not make any CFTR protein, and the company expects to share both safety and efficacy results from the MAD in the first half of 2025.
Type 1 Diabetes
VX-880, a stem cell-derived fully differentiated islet cell investigational therapy for people with type 1 diabetes and impaired hypoglycemic awareness, is advancing to pivotal development. Following successful regulatory interactions with the FDA, EMA, and MHRA, the current Phase 1/2 study will be converted into a Phase 1/2/3 study, including a total of 50 patients with difficult-to-control diabetes and severe hypoglycemic events despite optimal medical management. The primary endpoint is the proportion of patients achieving insulin independence with the absence of severe hypoglycemic events.
Data presented at EASD this September showed that four patients had 12 months of follow-up and all four achieved the primary and secondary endpoints, including elimination of severe hypoglycemic events, insulin independence, and ADA-recommended hemoglobin A1c levels of less than 7%. An additional five patients were off exogenous insulin as they progressed toward the 12-month primary endpoint evaluation.
IgA Nephropathy and Primary Membranous Nephropathy
Povetacicept (Pove), a dual antagonist of the BAFF and APRIL cytokines, is showing promise as a transformative medicine for patients with IgA nephropathy and potentially additional B-cell-mediated diseases. The global Phase 3 RAINIER study of Pove in patients with IgA nephropathy has begun, evaluating Pove 80 milligrams versus placebo on top of standard of care. The trial is designed with a preplanned interim analysis to evaluate proteinuria, which could support a potential accelerated approval in the U.S.
Updated Phase 2 data on patients with IgA nephropathy who received 80 milligrams of povetacicept demonstrated a mean 66% reduction from baseline in UPCR at 48 weeks with stable renal function. These results were accompanied by a 63% achievement of clinical remission. Emerging data from another renal B-cell mediated disease, primary membranous nephropathy, showed that treatment with Pove resulted in a mean 62% reduction from baseline in UPCR at 24 weeks, and two of the three patients achieved partial clinical remission.
Acute and Peripheral Neuropathic Pain
The FDA review of suzetrigine in moderate to severe acute pain is underway, with a PDUFA date of January 30, 2025. Phase 3 data from two RCTs and a single-arm safety and effectiveness trial were presented at the recent American Society of Anesthesiology Annual Meeting. In diabetic peripheral neuropathic pain, Vertex has initiated a Phase 3 pivotal program for suzetrigine and a Phase 2 study with the oral formulation of VX-993. In lumbosacral radiculopathy, the Phase 2 trial has been completed, and results are expected by the end of the year.
Myotonic Dystrophy Type 1
The Phase 1/2 clinical study of VX-670 in myotonic dystrophy type 1 (DM1) has accelerated, with the SAD portion of the trial completed and the MAD portion initiated. In the MAD, both safety and efficacy data will be collected, with the primary endpoint of safety and the secondary endpoint being the change from baseline in the splicing index on muscle biopsy.
