Vera Therapeutics, Inc. announced that it will host a virtual key opinion leader (KOL) event featuring Jonathan Barratt, PhD, FRCP, from the University of Leicester, who, together with Vera Therapeutics management, will provide an update on atacicept's ORIGIN Phase 2b data in IgA nephropathy (IgAN). Atacicept is the Company's potential best-in-class, disease-modifying dual inhibitor of the cytokines B lymphocyte stimulator (BLyS) and a proliferation-inducing ligand (APRIL). ORIGIN is a multinational, randomized, double-blind, placebo-controlled clinical trial (n=116) evaluating the efficacy and safety of atacicept in patients with IgAN who continue to have persistent proteinuria and remain at high risk of disease progression despite available ACE or ARB therapy.

Dr. Barratt leads the Renal Research Group within the College of Life Sciences, University of Leicester. His research is focused on a bench to bedside approach to improving understanding of the pathogenesis of IgAN, a common global cause of kidney failure. Jonathan is the IgAN Rare Disease Group lead for the UK National Registry of Rare Kidney Diseases (RaDaR), and a member of the steering committee for the International IgAN Network.

He works closely with pharmaceutical companies interested in new treatments for IgAN, is Chief Investigator for a number of international randomized controlled Phase 2 and 3 clinical trials in IgAN, and was a member of the FDA and American Society of Nephrology Kidney Health Initiative: Identifying Surrogate Endpoints for Clinical Trials in IgAN Workgroup. The ORIGIN clinical trial (NCT04716231) is a global, multicenter, randomized, double-blind, placebo-controlled Phase 2b trial evaluating the safety and efficacy of atacicept in 116 patients with IgAN who continue to have persistent proteinuria and remain at high risk of disease progression despite being on a stable prescribed regimen of RAASi for at least 12 weeks that is the maximum labeled or tolerated dose. The objectives of the study are to determine the effect of atacicept on proteinuria and preservation of renal function compared to placebo to determine the appropriate dose(s) for further clinical development.

The primary endpoint is the change in proteinuria as evaluated by UPCR at week 24 and the key secondary endpoint is the change in proteinuria as evaluated by UPCR at week 36. Additional exploratory endpoints include change in proteinuria as evaluated by UPCR at weeks 12, 48, and 96; change in estimated glomerular filtration rate (eGFR); change in serum immunoglobulin levels, and serum Gd-IgA1 levels; safety and tolerability; and serum pharmacokinetics (PK). The ORIGIN clinical trial evaluated three dose strengths of atacicept versus placebo, administered weekly by prefilled syringe, and their impact on the reduction of proteinuria as evaluated by urine protein to creatinine ratio (UPCR).

Patients were randomized 2:2:1:2 to atacicept 150 mg, atacicept 75 mg, atacicept 25 mg, or matching placebo. Upon completion of the 36-week blinded treatment period, all patients are being offered open-label atacicept 150 mg for an additional 60 weeks. 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% 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 investigational recombinant fusion protein that contains the soluble transmembrane activator and calcium-modulating cyclophilin ligand interactor (TACI) receptor that binds to the cytokines B lymphocyte stimulator (BLyS) 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 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 having been administered to more than 1,500 patients in clinical studies across different indications.