Vertex Reports Published Results for IgA Nephropathy Drug Ahead of FDA Decision

Rare Daily Staff

Vertex Pharmaceuticals said its experimental drug povetacicept substantially reduced protein in the urine in a phase 3 study of people with IgA nephropathy, a progressive kidney disease.

The results, published in the New England Journal of Medicine and presented at the American Society of Nephrology’s Kidney Week meeting, showed that povetacicept reduced protein in the urine by 49.8 percent compared with placebo after 36 weeks. The study is continuing to determine whether the treatment preserves kidney function over two years.

The U.S. Food and Drug Administration has set a November 30 target date to act on the company’s application for accelerated approval of povetacicept.

IgA nephropathy (IgAN) develops when abnormal immune complexes accumulate in the kidneys, triggering inflammation and scarring. The damage can allow protein and blood to leak into the urine and progressively impair the kidneys’ ability to filter waste.

Povetacicept blocks two immune-signaling proteins, BAFF and APRIL, that support the activity and survival of B cells. These immune cells contribute to the production of the antibodies involved in the disease. By blocking both signals, the treatment is intended to reduce the formation of damaging immune complexes.

The global RAINIER trial enrolled 605 adults across its main and exploratory groups to evaluate injections of povetacicept every four weeks against placebo, both given alongside standard care. The newly published findings come from a planned interim analysis at 36 weeks.

Participants receiving povetacicept had a 52 percent reduction from their starting levels of protein in the urine, measured using the urine protein-to-creatinine ratio, or UPCR. The reduction compared with placebo was 49.8 percent, meeting the study’s primary endpoint.

The study also found that 42.2 percent of participants receiving povetacicept reached a UPCR below 0.5 grams per gram, compared with 6.2 percent receiving placebo. Lower levels indicate less protein leaking through the kidneys.

The benefits occurred alongside optimized supportive care in both groups. Nearly two-thirds of participants (65.8 percent) were taking SGLT2 inhibitors, a class of medicines used to help protect kidney function.

Povetacicept also met two secondary endpoints. Levels of galactose-deficient IgA1, an abnormal form of an antibody involved in the disease, fell 77.4 percent from baseline in the treatment group, compared with a 9.1 percent increase in the placebo group. Among participants who had blood in their urine at the start of the study, it resolved in 85.1 percent receiving povetacicept, compared with 23.4 percent receiving placebo.

Vertex said most adverse events were mild or moderate. Upper respiratory tract infections occurred in 18.3 percent of participants receiving povetacicept and 11.4 percent receiving placebo. Injection-site reactions occurred in 14.5 percent and 2.2 percent, respectively.

The company reported no serious adverse events attributed to povetacicept, no opportunistic infections, and no deaths. No participants discontinued treatment because of infections.

If approved, Vertex plans to offer povetacicept as an at-home injection every four weeks using an autoinjector containing less than 0.5 milliliters of medicine. The company is also studying povetacicept in primary membranous nephropathy, another immune-mediated kidney disease, and generalized myasthenia gravis. Those programs remain separate from the pending IgAN application.

“At just 36 weeks 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,” said Carmen Bozic, chief medical officer of Vertex.

Photo: Carmen Bozic, chief medical officer of Vertex.