Vera Releases 36 Week Interim Analysis of Phase 2b Trial of Atacicept for the Treatment of IgA Nephropathy
January 30, 2023
Rare Daily Staff
Vera Therapeutics reported results from a prespecified per-protocol analysis of the phase 2b ORIGIN clinical trial of atacicept in patients with IgA nephropathy after reporting topline results on January 3, 2023.
IgA nephropathy (IgAN), or 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 (ESRD) or kidney failure, which has considerable morbidity and impact on patients’ lives.
Atacicept is Vera’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 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.
The ORIGIN clinical trial 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).
In the topline results published on January 3, 2023, all treated patients were included in the results as the intent-to-treat (ITT) population. In the prespecified PP analysis, the population was defined as patients who had completed treatment according to protocol, where 14 patients who had protocol violations identified by a blinded third-party CRO were excluded.
In the PP analysis, at Week 24, the atacicept 150 mg dose group achieved a 41 percent mean reduction in proteinuria versus baseline and a 34 percent delta versus placebo. With interim data at Week 36, the atacicept 150 mg dose group achieved a 47 percent mean reduction in proteinuria from baseline and a 48 percent delta 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 (AEs) and comparable rates of infection compared to placebo. Serious treatment-emergent AEs 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.
“We believe the PP analysis represents a more accurate assessment of treatment efficacy when compared to the ITT analysis, as it minimizes potential confounders for proteinuria measure. Our confidence in the promising clinical potential of atacicept is further bolstered by this analysis and we are rapidly advancing atacicept’s development as a potentially transformative therapy for patients with IgAN,” said Marshall Fordyce, CEO of Vera Therapeutics.
Vera is continuing to rapidly advance atacicept into pivotal phase 3 development, which is anticipated in the first half of 2023, subject to and following discussions with the FDA. The full data sets from the ORIGIN clinical trial will be presented at upcoming medical congresses. Vera plans to prioritize and focus current resources on the advancement of atacicept in IgAN into a pivotal phase 3 trial, extending cash runway to the fourth quarter of 2024. This updated cash runway guidance assumes a delay in enrollment in the pivotal phase 3 trial for lupus nephritis, and a delay of commitment of resources to the MAU868 program until regulatory agreement is reached regarding the pivotal phase 3 program for the treatment of BK viremia in kidney transplant recipients.
Photo: Marshall Fordyce, CEO of Vera Therapeutics
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