Vera Therapeutics Gains FDA Breakthrough Status for Atacicept in IgAN

Vera Therapeutics, Inc., a biotechnology firm based in Brisbane, California, has announced that the U.S. Food and Drug Administration (FDA) has awarded Breakthrough Therapy Designation to their drug atacicept for treating IgA nephropathy (IgAN). This designation indicates the FDA’s belief that atacicept shows significant promise over existing therapies for IgAN, based on data from the Phase 2b ORIGIN clinical trial.

Marshall Fordyce, M.D., the CEO of Vera Therapeutics, expressed optimism about the potential of atacicept to improve kidney function in IgAN patients, measured by estimated glomerular filtration rate (eGFR). He highlighted the upcoming release of long-term 96-week results from the Phase 2b ORIGIN trial later this year and the expected results from the pivotal Phase 3 ORIGIN 3 trial in the first half of 2025. These results are anticipated to support the regulatory approval submission for atacicept in IgAN.

The FDA’s Breakthrough Therapy Designation aims to expedite the development and review processes for drugs that treat serious conditions and have shown preliminary clinical evidence of substantial improvement over existing therapies. The Phase 2b ORIGIN trial demonstrated the stabilization of eGFR over 72 weeks of treatment with atacicept. Initially, participants received atacicept in a 36-week double-blind period, followed by an additional 36 weeks of open-label follow-up where they continued to self-administer 150 mg of atacicept subcutaneously once a week at home. The stabilization of eGFR in patients was more consistent with the general population compared to those with IgAN, indicating a substantial improvement over current therapies.

The Phase 2b ORIGIN clinical trial was a global, multicenter, randomized, double-blind, placebo-controlled study evaluating the safety and efficacy of atacicept in 116 patients with IgAN who had persistent proteinuria despite being on a stable regimen of renin-angiotensin-aldosterone system inhibitors (RAASi) for at least 12 weeks. The trial assessed three doses of atacicept against a placebo, with participants randomized into different groups. The primary endpoint was measured by changes in proteinuria by urine protein to creatinine ratio (UPCR) at week 24, while the secondary endpoint was measured at week 36. The trial met its primary and secondary endpoints, showing significant reductions in proteinuria and stabilization of eGFR compared to placebo, with a comparable safety profile.

The Phase 3 ORIGIN 3 trial is another global, multicenter, randomized, double-blind, placebo-controlled study designed to evaluate the safety and efficacy of 150 mg atacicept in IgAN patients. Participants will undergo a 4-week screening period, a 104-week double-blind treatment, followed by a 52-week open-label extension and 26 weeks of follow-up. The primary endpoint focuses on changes in proteinuria at week 36, while the key secondary endpoint examines the annualized rate of change in eGFR up to week 104.

IgAN, also known as Berger’s disease, is a serious autoimmune kidney disorder that lacks effective treatments. It is characterized by the production of immunogenic Gd-IgA1, triggering autoantibodies that form pathogenic immune complexes, leading to kidney inflammation and damage. Up to 50% of IgAN patients may progress to end-stage kidney disease (ESKD) or kidney failure.

Atacicept is an investigational recombinant fusion protein targeting B-cell Activating Factor (BAFF) and A Proliferation-Inducing Ligand (APRIL), which promote B-cell survival and autoantibody production in autoimmune diseases like IgAN and lupus nephritis. Vera Therapeutics is also developing MAU868, a monoclonal antibody to neutralize BK virus infections, particularly in kidney transplant settings. Vera Therapeutics retains all global developmental and commercial rights to both atacicept and MAU868, focusing on advancing these treatments to address significant unmet medical needs in immunological diseases.