Injection therapy reduces kidney damage marker in IgAN trial
Povetacicept lowers excess protein in urine, interim results from Phase 3 trial show
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Trial data showed povetacicept may lower urine protein. (Photo by iStock)
The experimental injection therapy povetacicept is superior to a placebo at reducing excess protein in urine (proteinuria), a marker of kidney damage, in adults with immunoglobulin A nephropathy (IgAN).
That’s according to interim results from the global Phase 3 RAINIER clinical trial (NCT06564142), which showed that the study met both the main and secondary goals of its initial, eight-month analysis.
The findings were published in The New England Journal of Medicine in a study titled, “Interim Analysis of a Phase 3 Trial of Povetacicept in IgA Nephropathy,” and presented last week at the American Society of Nephrology Kidney Week 2026. The work was funded by Vertex Pharmaceuticals, the company developing povetacicept.
“At just 36 weeks [eight months] of treatment, povetacicept has delivered impressive efficacy results, together with favorable safety and convenient dosing at-home every 4 weeks in a low-volume auto-injector that can fit into the lives of IgAN patients, underscoring the potential of povetacicept to substantially impact and redefine expectations for disease control in IgAN,” Carmen Bozic, MD, executive vice president of global medicines development and medical affairs and chief medical officer at Vertex, said in a company press release.
Richard Lafayette, MD, the study’s senior author, Stanford University Medical Center professor, and co-chair of the RAINIER steering committee, said the results “are among the most compelling I have seen in IgAN and highlight the potential of povetacicept to become an important new treatment option for patients living with this chronic progressive disease.”
FDA decision on accelerated approval expected this month
Vertex said the results support its U.S. Food and Drug Administration application seeking accelerated approval of povetacicept for adults with IgAN, and the company said it is on track to receive a decision by Nov. 30.
Accelerated approval allows an experimental therapy to be marketed based on preliminary evidence from clinical trials supporting its therapeutic potential — in povetacicept’s case, the observed reduction in proteinuria. To achieve full approval, the company would have to submit additional clinical trial results confirming the therapy’s benefits.
IgAN is a rare autoimmune disorder in which an abnormal antibody, galactose-deficient IgA1 (Gd-IgA1), triggers the formation of molecular clusters called immune complexes. These complexes build up in the kidneys, driving damaging inflammation. These disease-driving antibodies are produced by B-cells, a type of immune cell.
Administered once a month via under-the-skin injection, povetacicept is designed to block APRIL and BAFF, two signaling molecules that promote B-cell activation. The therapy is therefore expected to reduce the production of disease-driving antibodies.
“Povetacicept was specifically designed as a high-potency, high-affinity [B-cell-targeting] fusion protein with broad tissue distribution to deliver this dual [suppression] in order to target upstream [disease-driving] immune complex production,” Lafayette said.
The RAINIER study is testing povetacicept against a placebo in more than 600 adults with IgAN over two years. The trial’s main goal at 36 weeks was to see if povetacicept was superior to the placebo at reducing proteinuria, as measured with a standardized value called the urinary protein-to-creatinine ratio (UPCR).
This goal was met, with povetacicept-treated patients showing a 52% mean UPCR reduction, compared with a 4.3% reduction in those on the placebo, reflecting a 49.8% difference between the groups.
In addition, nearly half (42.2%) of patients on the therapy and 6.2% of those given the placebo had UPCR levels below 0.5 g/g, the threshold aligned with current kidney care guidelines for low risk of kidney disease progression.
The study also met its two secondary goals at 36 weeks. Povetacicept led to significantly greater decreases in Gd-IgA1 levels relative to the placebo and helped significantly more patients resolve their hematuria, or blood in urine (85% vs. 23%).
“Importantly, these findings were observed on top of optimized supportive [kidney] care in both treatment arms, including sodium-glucose co-transporter 2 (SGLT2) inhibitor use in 65.8% of participants,” the company said.
Safety data were positive overall. A few serious safety issues were documented, but none was judged to be related to the therapy, and only one patient on povetacicept discontinued treatment due to safety issues.
“In this planned interim analysis of a phase 3 trial, adults with IgA nephropathy who received povetacicept had rapid and significant reductions in proteinuria, galactose-deficient IgA1 levels, and hematuria, which are considered to be key markers of kidney-function preservation” in this patient population, the researchers wrote.
If povetacicept is approved, Vertex plans to launch the therapy as an autoinjector, a device that is held against the skin and injects a therapy at the touch of a button. With a traditional syringe, it’s necessary to physically insert a needle through the skin and then push the plunger to administer a drug.
According to Vertex, interviews with 25 IgAN patients living in the U.S. found that all but one preferred an autoinjector to a traditional syringe.
The company also announced the launch of a Phase 3b trial, PAVANT (NCT07890909), designed to assess user experience with povetacicept’s autoinjector compared with Voyxact (sibeprenlimab-szsi), an IgAN-approved therapy administered via a prefilled syringe. The study is expected to enroll up to 40 adults with IgAN.
