Vertex Shows Promising Phase 1/2 Data for Povetacicept in IgA Nephropathy and Primary Membranous Nephropathy at ASN Kidney Week 2025

Vertex Pharmaceuticals updated the nephrology community at the 2025 ASN Kidney Week with new Phase 1/2 data from their RUBY-3 clinical trial evaluating Povetacicept in adults with two severe kidney diseases: IgA nephropathy (IgAN) and primary membranous nephropathy (pMN). Povetacicept is a novel fusion protein that uniquely targets and inhibits both BAFF (B cell activating factor) and APRIL (a proliferation-inducing ligand), molecular drivers involved in pathogenic antibody production in these autoimmune-related kidney disorders.

The RUBY-3 study is an open-label trial where patients receive subcutaneous doses of Povetacicept every four weeks. The updated 48-week data encompasses 21 IgAN patients and 10 pMN patients treated at the 80 mg dose level with follow-up completion in the majority.

In IgAN patients, Povetacicept treatment resulted in a remarkable 64% mean reduction in 24-hour urine protein to creatinine ratio (UPCR), a key marker of kidney damage. Kidney function as measured by estimated glomerular filtration rate (eGFR) remained stable with a slight mean increase, indicating preservation of renal function. Hematuria resolution, a measure of blood in urine and an inflammation sign, was achieved in 90% of patients who had moderate or large blood presence at baseline. Clinical remission, defined as UPCR below 0.5 g/g, absence or minimal hematuria, and less than 25% decline in eGFR, was observed in 53% of treated patients.

Among patients with pMN, an even greater 82% reduction in UPCR was reported at 48 weeks. Kidney function remained stable with negligible eGFR change. Clinical remission, defined similarly to IgAN but adapted for pMN, was achieved in 40% of participants. Povetacicept was well tolerated in both patient groups, with mild to moderate adverse events and no serious events attributed to the drug.

The efficacy and safety profile from RUBY-3 reinforces povetacicept’s potential as a best-in-class therapy in these two immune-mediated kidney diseases where treatment options remain limited. This dual BAFF/APRIL inhibition targets pathogenic B cell mechanisms believed to underlie disease progression.

Regulatory milestones include the FDA granting Breakthrough Therapy Designation for Povetacicept in IgAN. Vertex plans to submit a rolling Biologics License Application (BLA) for accelerated approval and intends to use a priority review voucher to expedite evaluation. The pivotal Phase 3 RAINIER trial for IgAN is fully enrolled. For pMN, Vertex has Fast Track designation and is progressing the pivotal Phase 2/3 OLYMPUS trial.

James Tumlin, M.D., Principal Investigator of RUBY-3 and Professor at Emory University, highlighted that the data demonstrate the transformative potential of BAFF+APRIL inhibition in treating serious kidney diseases, with two-thirds of IgAN patients achieving complete response at 48 weeks per KDIGO guidelines

Richard Lafayette, M.D., Steering Committee Member for the RAINIER trial and Professor at Stanford University Medical Center, emphasized the urgent need for effective treatments in IgAN and pMN, noting the rapid RAINIER enrollment and excitement for povetacicept’s dual BAFF+APRIL approach supported by RUBY-3 data.

Overall, these updated RUBY-3 results presented as a late-breaking oral presentation at ASN Kidney Week 2025 highlight substantial clinical benefits with sustained proteinuria reduction, kidney function preservation, and remission induction, positioning Povetacicept as a promising treatment in IgAN and pMN.