RANIER: Povetacicept Achieves Primary and All Secondary Endpoints for IgAN

Povetacicpet met its primary and secondary endpoints in RANIER, an ongoing phase 3 trial evaluating in adults with IgA nephropathy (IgAN), according to a 36-week interim analysis.1

Vertex Pharmaceuticals Incorporated announced the positive results on March 9, 2026, where povetacept showed a 52.0% reductio in urine protein to creatinine ratio (UPCR) compared to baseline, with a statistically significant and clinically meaningful 49.8% UPCR reduction compared to placebo (P < .0001)1

“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,” said Reshma Kewalramani, MD, Chief Executive Officer and President of Vertex, in a statement. “These results are important for patients with IgAN and also bring us one step closer to realizing povetacicept’s pipeline-in-a-product promise”1

Povetacicept is an engineered fusion protein and dual inhibitor of the B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) cytokines. APRIL primarily supports plasma cell survival and function, and BAFF regulates early pathogenic B-cell development, activates pathogenic T cells and innate immune cells, and contributes to mesangial cell proliferation and podocyte injury.1

Previously evaluated in phase 1/2 RUBY-3 trial, povaticept led to substantial, sustained UPCR reductions with stable eGFR, significant Gd-IgA1 reductions, hematuria resolution, clinical remission, with favorable safety in IgAN and primary membranous nephropathy (pMN), according to data presented at the American Society of Nephrology (ASN) Kidney Week 2025. Povetacicept has received Breakthrough Therapy Designation from the US Food and Drug Administration (FDA) for the treatment of IgAN, along with a rolling review for the Biologic License Application (BLA).1,2

Accordingly, the randomized, double-blind, placebo-controlled pivotal phase 3 RANIER trial evaluated the efficacy of povetacicept in reducing proteinuria and preserving renal function. The study included 605 patients who were randomized to receive 80 mg povetacicept administered subcutaneously every four weeks on top of standard care or placebo.1

For the interim analysis, the trial’s primary endpoint is the change in 24-hour UPCR, and the 2 alpha-controlled secondary endpoints are the change in serum galactose-deficient IgA1 (Gd-IgA1) and the proportion of patients to achieve hematuria resolution at week 36. Additionally, the exploratory endpoints included the proportion of patients with 24-hour UPCR <0.5 g/g, in line with the most recent Kidney Disease: Improving Global Outcomes (KDIGO) guidelines.1

For the first secondary endpoint, patients treated with povetacicept demonstrated a 77.4% reduction in Gd-IgA1 compared to an increase of +9.1% in the placebo group, yielding a reduction of 79.3% compared to placebo (P <.0001) from baseline.1

For the second secondary endpoint, in patients with baseline hematuria, 85.1% achieved hematuria resolution in the povetacicept treatment group compared to 23.4% in the placebo group, resulting in hematuria resolution of 61.7% compared to placebo (P <.0001).1

Overall, povetacicept was generally safe and well-tolerated and the majority of adverse events (AEs) were mild to moderate.1

RAINIER is the largest trial conducted in IgAN so far, having achieved full enrollment faster than any contemporary one. If povetacicept is approved by the FDA, Vertex plans to launch povetacicept in a low-volume (<0.5 mL) subcutaneous auto-injector delivered once every 4 weeks via at-home administration.1

The RAINIER Phase 3 trial will continue with final analysis at 2 years of treatment, and a primary endpoint of total estimated glomerular filtration rate (eGFR) slope through Week 104.1

References

1. Vertex Announces Positive Week 36 Interim Analysis Results for Primary and All Secondary Endpoints in the RAINIER Phase 3 Trial of Povetacicept in Adults With IgA Nephropathy | Vertex Pharmaceuticals Newsroom. Vertex Pharmaceuticals Newsroom. Published 2026. Accessed March 9, 2026. https://news.vrtx.com/news-releases/news-release-details/vertex-announces-positive-week-36-interim-analysis-results

2. Tumlin J. Povetacicept Data Validate APRIL/BAFF Inhibition in IgAN and pMN, With James Tumlin, MD. Hcplive.com. Published November 13, 2025. Accessed March 9, 2026. https://www.hcplive.com/view/povetacicept-data-validate-april-baff-inhibition-igan-pmn-tumlin