A Vertex Pharmaceuticals immunology drug in clinical testing for a rare kidney disease is catching up to others that work in a similar way, but the company contends its therapy can be best in its class. Vertex is building that case with fresh Phase 3 data showing the experimental treatment significantly cut levels of a protein that’s a biological sign of the disease, setting up plans to seek an accelerated FDA approval that could bring this drug to the market by the end of 2026.
The Vertex drug, povetacicept, is in development for immunoglobulin A nephropathy (IgAN), a disease in which the body produces autoantibodies that damage the kidney. After Monday’s market close, Vertex reported that a pre-specified interim analysis of the Phase 3 study at 36 weeks showed monthly dosing of the drug led to a 52% reduction, from baseline, in the levels of urine proteins that indicate kidney disease, meeting one of the main study goals. Relative to placebo, this reduction was 49.8%.
The study’s other main goal is measuring estimated glomerular filtration rate, a test of how well kidneys filter waste. Vertex said this measure will be announced at week 104, when the study ends. The study drug was safe and well tolerated, with the majority of adverse events reported to be mild to moderate.
Povetacicept came from Vertex’s $4.9 billion acquisition of Alpine Immune Sciences in 2024. The drug is a fusion protein engineered to inhibit BAFF and APRIL, two signaling proteins that drive IgAN. At the time of the deal, Alpine was also exploring applications of its drug to other immunological disorders driven by BAFF and APRIL. Vertex aims to top other companies going after one or both of those targets.
Otsuka Pharmaceuticals’ Voyxact, an antibody designed to block APRIL, won accelerated FDA approval in IgAN last November. In its pivotal test, the once-monthly injected Otsuka drug showed a 51% placebo-adjusted reduction in urine proteins indicative of the disease.
Vera Therapeutics might be next to reach the IgAN market with atacicept, a fusion protein engineered to block both APRIL and BAFF. In its pivotal test, the drug led to a 42% placebo-adjusted reduction in urine proteins measured at week 36. The FDA is currently reviewing this drug, which faces a July 7 target date for a regulatory decision. Meanwhile, Vor Biopharma is also developing a fusion protein that blocks APRIL and BAFF, but has prioritized other autoimmune indications.
In a research note, Leerink Partners analyst David Risinger said povetacicept’s dosing and administration profile is more convenient compared to competitors. The Vertex drug is administered monthly via a small-volume auto-injector that patients can do at home. Otsuka’s drug may also be self-administered monthly, but it comes in a larger-volume pre-filled syringe, and Risinger noted that Vertex management has said the smaller-volume dose could be a differentiator. Meanwhile, Vera’s IgAN drug is administered as a weekly injection.
William Blair sees the povetacicept data as “a clear win for Vertex,” analyst Myles Minter said in a research note. Acknowledging that Vertex will enter the IgAN market behind Otsuka and likely Vera, he said povetacicept’s superior risk/benefit profile and once-monthly dosing via an autoinjector will ensure class-leading potential. The bank has modeled $2.1 billion in peak povetacicept sales, which assumes only a 17% peak penetration rate into the IgAN population. William Blair also noted the drug’s potential to treat other autoinflammatory disorders; a Phase 2 study in generalized myasthenia gravis is expected to start in the first half of this year.
Povetacicept’s biologics license application has been submitted to the FDA on a rolling basis and Vertex said the full submission seeking accelerated approval will be complete by the end of the month. The company added that it will use a priority review voucher to cut the review time from 10 months to six, which could lead to a regulatory decision in the fourth quarter of this year. In a prepared statement, Vertex CEO Reshma Kewalramani said povetacicept’s results establish renal medicine as Vertex’s fourth therapeutic area of focus, alongside cystic fibrosis, hematology, and acute pain.
“As a nephrologist, I am struck by the rapid, deep and sustained response to povetacicept, as well as the consistency of benefit across all subgroups,” she said. “These results are important for patients with IgAN and also bring us one step closer to realizing povetacicept’s pipeline-in-a-product promise.”
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