Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) announced updates on its kidney disease pipeline, which includes treatments for IgA nephropathy (IgAN), primary membranous nephropathy (pMN), and APOL1-mediated kidney disease (AMKD). These updates highlight the transformative potential of Vertex’s investigational therapies and include promising new data on povetacicept, a dual inhibitor of the BAFF and APRIL pathways, presented at the American Society of Nephrology (ASN) Kidney Week Congress, held from October 23-27 in San Diego, California.
“We are excited about the expansion of our innovative pipeline in renal medicine, which now encompasses programs for AMKD, IgAN, pMN, and polycystic kidney disease,” said Carmen Bozic, M.D., Executive Vice President of Global Medicines Development and Medical Affairs and Chief Medical Officer at Vertex. “The new data presented at ASN reinforce povetacicept’s potential as a best-in-class therapy and illustrate its promise as a pipeline-in-a-product. We are also advancing treatments for AMKD and autosomal dominant polycystic kidney disease (ADPKD), targeting the underlying causes of these conditions.”
Povetacicept in IgAN
Vertex presented data on 54 patients with IgAN who received povetacicept at doses of 80 mg or 240 mg subcutaneously every four weeks. The 80 mg dose demonstrated a significant mean reduction of 66% in the urine protein to creatinine ratio (UPCR) at 48 weeks (n=8), with stable renal function as measured by estimated glomerular filtration rate (eGFR). By week 48, 63% (5 out of 8) of participants achieved clinical remission, defined as UPCR <0.5 g/g, negative hematuria, and stable renal function (<25% reduction in eGFR from baseline).
The 240 mg dose also showed similar benefits in reducing proteinuria while maintaining stable renal function. Both doses were well tolerated, with most adverse events (AEs) being mild or moderate, and no serious adverse events (SAEs) related to povetacicept were reported.
Vertex has initiated the RAINIER global Phase 3 clinical trial of povetacicept 80 mg for IgAN.
A poster titled “Results from Longer Follow-Up with Povetacicept, an Enhanced Dual BAFF/APRIL Antagonist, in IgA Nephropathy (RUBY-3 Study)” was presented on October 25 during the poster session from 10:00 a.m. to 12:00 p.m. PDT.
Povetacicept in pMN
Emerging data were also shared for patients with pMN receiving povetacicept 80 mg SC Q4W, with three patients having completed at least 24 weeks of treatment. The treatment resulted in a mean 62% reduction in UPCR at 24 weeks, alongside stable renal function. By week 24, 67% (2 out of 3) of participants achieved partial clinical remission, defined as UPCR <3.5 g/g and a >50% reduction from baseline. Anti-PLA2R1 autoantibodies, a disease activity marker, decreased by an average of 87% at week 20.
Povetacicept was well tolerated, with AEs that were primarily mild or moderate, and no SAEs associated with the treatment.
A poster titled “Updated Results with Povetacicept, an Enhanced Dual BAFF/APRIL Antagonist, in Primary Membranous Nephropathy (RUBY-3 Study)” was presented on October 24 from 10:00 a.m. to 12:00 p.m. PDT.
AMKD
Vertex is developing inaxaplin, a potential first-in-class oral small molecule inhibitor of APOL1, targeting the underlying cause of AMKD. Enrollment and dosing are ongoing in the Phase 3 portion of the pivotal AMPLITUDE clinical trial.
