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Vera Therapeutics Reports Positive Data from Phase 2 Extension Study in IgAN

January 25, 2024

Rare Daily Staff

Vera Therapeutics reported positive 72-week data from the open label extension period of its phase 2b ORIGIN clinical trial of atacicept in participants with IgA nephropathy.

Richard Lafayette, professor of Medicine, Nephrology and director of the Stanford Glomerular Disease Center at Stanford University Medical Center, said data from the open label extension show consistent and sustained improvements in participants with IgAN, which he said “represents an important potential advancement for IgAN patients and has potential implications for the future treatment paradigm in this disease.”

IgA nephropathy (IgAN), also known as Berger’s disease, is a serious and progressive autoimmune disease of the kidney, for which there remains a high unmet medical need. IgAN is driven by the production of immunogenic Gd-IgA1, which triggers autoantibodies that lead to the formation of pathogenic immune complexes, which become trapped in the kidney’s glomeruli, causing inflammation and progressive damage. In up to 50 percent of patients, IgAN can lead to end-stage renal disease (ESRD) or kidney failure, which has considerable morbidity and impact on patients’ lives.

Atacicept is an experimental recombinant fusion protein that contains the soluble transmembrane activator and calcium-modulating cyclophilin ligand interactor (TACI) receptor that binds to the cytokines B-cell activating factor (BAFF) and A proliferation-inducing ligand (APRIL). These cytokines are members of the tumor necrosis factor family that promote B-cell survival and autoantibody production associated with certain autoimmune diseases, including IgAN and lupus nephritis.

The phase 2b ORIGIN clinical trial of atacicept in IgAN met its primary endpoint and showed a statistically significant reduction in mean proteinuria versus baseline at weeks 24 and 36. Vera believes atacicept is positioned for best-in-class potential, targeting B cells and plasma cells to reduce autoantibodies and having been administered to more than 1,500 patients in clinical studies across different indications.

After completing the 36-week randomized, double-blind, placebo-controlled period of the phase 2b ORIGIN trial, all participants were eligible to receive atacicept 150 mg in the open label expansion study (OLE). Of the 116 randomized participants, 106 completed 72 weeks.

Participants treated with atacicept for 72 weeks demonstrated a 62 percent reduction in Gd-IgA1, a reduction in the percentage of participants with hematuria to 19 percent, and a 48 percent reduction in UPCR in the per-protocol (PP) analysis. Importantly, participants had consistent and stable eGFR with mL/min/1.73m2 change from baseline at 72 weeks. Of note, it has been shown that eGFR declines by approximately 1 mL/min/1.73m2 per year in the general population.

Participants who switched from placebo to atacicept demonstrated similar outcomes across each of the key indicators of IgAN as compared to participants originally randomized to atacicept during the first 36 weeks of the trial, including a 59 percent reduction in Gd-IgA1, a reduction in the percentage of participants with hematuria to 41 percent, and a 47 percent reduction in UPCR in the PP analysis.

In addition, eGFR stabilization was observed in participants who switched from placebo to atacicept with a -3.2 mL/min/1.73m2 change from baseline at 72 weeks compared to -4.9 mL/min/1.73m2 at 36 weeks.

Safety data in the open label extension were consistent with the randomized period and indicated that atacicept was generally well-tolerated. These data build upon the prior experience of atacicept in randomized, double-blind, placebo-controlled clinical trials in which atacicept was generally well-tolerated.

Vera’s ongoing pivotal ORIGIN 3 trial is currently underway, with enrollment on track to be completed in the second half of 2024.

“We believe these data further support our belief that atacicept has the disruptive potential to stand out as a disease-modifying treatment for patients with IgAN,” said Marshall Fordyce, CEO of Vera Therapeutics.

Photo: Marshall Fordyce, CEO of Vera Therapeutics

 

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