Analysis of week 36 data from Phase 2b ORIGIN study shows atacicept 150 mg substantially reduces serum Gd-IgA1 and resolves hematuria in the majority of patients.
Additional poster presentations provide further safety analysis of Phase 2b and details of pivotal Phase 3 clinical trial design, which is currently enrolling.
BRISBANE, Calif., Nov. 04, 2023 (GLOBE NEWSWIRE) -- Vera Therapeutics, Inc. (Nasdaq: VERA), a late-stage biotechnology company focused on developing and commercializing transformative treatments for patients with serious immunological diseases, today announced the presentation of three posters – including an additional analysis of week 36 data from the Phase 2b ORIGIN study demonstrating resolution of hematuria in the majority of patients – on the Company’s product candidate atacicept in patients with immunoglobulin A nephropathy (IgAN) at the American Society of Nephrology (ASN) Kidney Week 2023, in Philadelphia, PA.
Hematuria is an important indication of IgAN activity representing active inflammation of glomeruli. At week 36 of the ORIGIN Phase 2b study of atacicept in patients with IgAN, hematuria resolved in 80% of patients (n=12/15) receiving atacicept 150 mg compared to 5% (n=1/19) in the placebo group.
High serum levels of galactose-deficient IgA1 (Gd-IgA1) are associated with greater risk of end-stage renal disease or death. Patients on atacicept 150 mg achieved durable and significant Gd-IgA1 reduction over 36 weeks where regardless of baseline quartile, 82% of patients (n=27/33) achieved reduction to the lowest risk quartile. Gd-1gA1 reduction was also correlated with improvement in hematuria at week 36 (r=0.35, p=0.0003).
“Today’s finding that hematuria – clinical evidence of active nephritis – resolves in the majority of patients receiving atacicept, supports an additional therapeutic benefit of targeting the source of this disease through atacicept’s dual inhibition of BAFF and APRIL,” said Marshall Fordyce, M.D., Chief Executive Officer of Vera Therapeutics. “We look forward to presenting open-label extension eGFR and proteinuria data throughout the first half of 2024 and are on track with enrollment of our pivotal Phase 3 ORIGIN 3 trial.”
An additional poster presented at Kidney Week 2023 details further safety results from the randomized, placebo-controlled period of the Phase 2b ORIGIN trial, which are consistent with the previously observed safety profile of atacicept. This analysis assessed vaccine response and immunity with atacicept in an IgAN population.
Through the randomized, placebo-controlled period, infections were balanced between atacicept and placebo in both the Phase 2a JANUS and Phase 2b ORIGIN studies. Additionally, atacicept treatment was associated with continued protective immunity to diphtheria and tetanus in the JANUS study, as measured at day 1, week 48 and week 72. In the Phase 2b ORIGIN study, the atacicept and placebo groups had similar rates of overall and COVID-19 infections, and most COVID-19 infections were mild in severity and did not cause any study discontinuations.
- Phase 2b open-label extension data, including eGFR and UPCR, expected in 1H 2024
- Phase 3 enrollment expected to complete in 2H 2024
The posters presented at ASN Kidney Week 2023 will be available on the Company’s website at https://veratx.com/publications/.
About the Phase 2b ORIGIN clinical trial
The Phase 2b ORIGIN clinical trial (NCT04716231) is a global, multicenter, randomized, double-blind, placebo-controlled 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 urine protein to creatinine ratio (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 Phase 2b ORIGIN clinical trial evaluated three dose strengths of atacicept versus placebo, administered weekly by prefilled syringe. 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 offered open-label atacicept 150 mg for an additional 60 weeks.
The trial met its primary and key secondary endpoints, with statistically significant and clinically meaningful proteinuria reductions and stabilization of eGFR versus placebo through week 36. Safety was comparable between atacicept and placebo.
For more information about the Phase 2b ORIGIN clinical trial, please visit www.clinicaltrials.gov.
About the Pivotal Phase 3 clinical trial (ORIGIN 3)
The ORIGIN 3 clinical trial (NCT04716231) is a global, multicenter, randomized, double-blind, placebo-controlled Phase 3 trial evaluating the safety and efficacy of atacicept 150 mg in 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 RASi (ACEi or ARB) for at least 12 weeks that is the maximum labeled or tolerated dose. The objectives of the trial are to determine the effect of atacicept on proteinuria and preservation of renal function compared to placebo.
The Phase 3 trial is composed of up to a 4-week screening period, a 104-week double-blind treatment period, a 52-week open-label extension and 26 weeks of follow-up. Participants will be randomized 1:1 to atacicept 150 mg once weekly subcutaneous injections (N=188) or placebo once weekly subcutaneous injections (N=188) for 104 weeks, followed by a 52-week open-label extension. The primary endpoint is the change from baseline in proteinuria as evaluated by urine protein to creatinine ratio (UPCR) at week 36. The key secondary endpoint is annualized rate of change in estimated glomerular filtration rate (eGFR) up to week 104. Additional secondary endpoints are the change in Gd-IgA1, change in eGFR up to week 52, and time from randomization to first occurrence of composite kidney failure endpoint event.
For more information about the ORIGIN 3 clinical trial, please visit www.clinicaltrials.gov.
About IgA nephropathy (IgAN), or Berger’s disease
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 (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-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 IgA nephropathy 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.
Vera Therapeutics is a late-stage biotechnology company focused on developing treatments for serious immunological diseases. Vera’s mission is to advance treatments that target the source of immunologic diseases in order to change the standard of care for patients. Vera’s lead product candidate is atacicept, a fusion protein self-administered as a subcutaneous injection once weekly that blocks both B-cell activating factor (BAFF) and A proliferation-inducing ligand (APRIL), which stimulate B cells and plasma cells to produce autoantibodies contributing to certain autoimmune diseases, including IgA nephropathy (IgAN), also known as Berger’s disease, and lupus nephritis. In addition, Vera is evaluating additional diseases where the reduction of autoantibodies by atacicept may prove medically useful. Vera is also developing MAU868, a monoclonal antibody designed to neutralize infection with BK Virus, a polyomavirus that can have devastating consequences in certain settings such as kidney transplant. Vera retains all global developmental and commercial rights to atacicept and MAU868. For more information, please visit www.veratx.com.
Statements contained in this press release regarding matters, events or results that may occur in the future are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements include statements regarding, among other things, Vera’s anticipated poster presentations at the American Society of Nephrology Kidney Week 2023, atacicept being positioned for best-in-class potential, Vera’s expectations regarding completing enrollment of the pivotal Phase 3 ORIGIN 3 trial, the design and management of such trial, expectations regarding reporting longer term results from Vera’s Phase 2b ORIGIN clinical trial and Vera’s product candidates, strategy, and regulatory matters. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Words such as “potential,” “will,” “plan,” and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based upon Vera’s current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, which include, without limitation, risks related to the regulatory approval process, results of earlier clinical trials may not be obtained in later clinical trials, preliminary results may not be predictive of topline results, risks and uncertainties associated with Vera’s business in general, the impact of macroeconomic and geopolitical events, and the other risks described in Vera’s filings with the Securities and Exchange Commission. All forward-looking statements contained in this press release speak only as of the date on which they were made and are based on management’s assumptions and estimates as of such date. Vera undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made, except as required by law.