Vera Therapeutics reported its experimental therapy atacicept met its primary endpoint in the phase 2b ORIGIN clinical trial in people with the rare and progressive autoimmune condition immunoglobulin A nephropathy.
Photo: Marshall Fordyce, CEO of Vera Therapeutics
Immunoglobulin A 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 galactose-deficient IgA1 (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 or kidney failure, which has considerable morbidity and impact on patients’ lives.
Atacicept is an investigational recombinant fusion protein that contains the soluble transmembrane activator and calcium-modulating cyclophilin ligand interactor receptor that binds to the cytokines B lymphocyte stimulator and a proliferation-inducing ligand. These cytokines are members of the tumor necrosis factor family that promote B-cell survival and autoantibody production associated with certain autoimmune diseases, including IgA nephropathy and lupus nephritis. Atacicept showed a dose-dependent effect on key biomarkers and clinical markers in a phase 2a clinical study. Vera believes atacicept is positioned for best-in-class potential, targeting B cells and plasma cells to reduce autoantibodies and has been administered to more than 1,500 patients in clinical studies across different indications.
“IgAN is a serious and progressive autoimmune disease of the kidney that can severely impact quality of life as up to half of patients develop end-stage kidney disease, requiring dialysis or kidney transplant within 20 years of diagnosis,” said Jonathan Barratt, The Mayer Professor of Renal Medicine, University of Leicester, U.K. “The positive topline results from the ORIGIN clinical trial demonstrate atacicept’s ability to reduce Gd-IgA1, the source of this disease, which in turn leads to clinically meaningful reductions in proteinuria at an early, 24-week time point, and is strongly supportive of a long-term benefit on kidney function.”
The primary endpoint analysis, change in proteinuria as evaluated by urine protein creatinine ratio at week 24 of the pooled 75/150 mg dose groups, achieved statistical significance and showed a 31 percent mean reduction versus baseline. Statistical significance was also achieved in the individual 150 mg dose group with a 33 percent mean reduction in proteinuria versus baseline and the all-atacicept group versus placebo.
Safety results indicated that atacicept was generally well-tolerated and were consistent with the previously observed safety profile of atacicept, including a 1 percent discontinuation rate due to adverse events and comparable rates of infection compared to placebo. Serious treatment-emergent adverse events were observed in 2 percent of patients in all atacicept arms and in 9 percent of patients in the placebo arm. These results build upon the prior integrated analysis of atacicept in randomized, double-blind, placebo-controlled clinical trials in more than 1,500 patients to date—in which atacicept was well-tolerated.
As a result of these positive data, Vera plans to advance atacicept into pivotal phase 3 development in the first half of 2023, subject to and following discussions with the U.S. Food and Drug Administration. The full data sets from the ORIGIN clinical trial will be presented at a future medical meeting.
“This is an important milestone not only for Vera but for the entire IgAN community,” said Marshall Fordyce, CEO of Vera Therapeutics. “Atacicept could be a transformational treatment for patients with IgAN who currently have limited treatment options.”
Author: Rare Daily Staff
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