Vera Therapeutics (NASDAQ:VERA) reported final efficacy results from its Phase III ORIGIN trial evaluating atacicept, marketed as TRUTAKNA, in adults with IgA nephropathy. The company presented the data at the American Society of Nephrology’s Kidney Week meeting in Denver, alongside publication in The New England Journal of Medicine.
The randomized, placebo-controlled global study evaluated weekly self-administered subcutaneous atacicept 150 mg in adults with IgA nephropathy who had persistent proteinuria despite optimized supportive care. According to Jonathan Barratt, Mayer Professor of Medicine at the University of Leicester, the enrolled population had an average estimated glomerular filtration rate, or eGFR, of about 65 mL/min and proteinuria of 2.2 grams per day. Most participants were receiving renin-angiotensin system inhibitors, while 60% to 65% were also using SGLT2 inhibitors.
Kidney Function and Composite Endpoint Results
Barratt said atacicept produced a placebo-adjusted eGFR difference of 5.6 mL/min at week 52 and 11.1 mL/min at week 104. The annualized placebo-adjusted difference in eGFR slope was 5 mL/min per year.
Patients receiving atacicept lost less than 1 mL/min of kidney function annually, according to Barratt, which he said is consistent with the treatment target outlined in KDIGO guidance. In contrast, he said patients in the placebo arm experienced substantially faster kidney-function loss.
The study also showed a 76% reduction through week 104 in the composite kidney disease progression endpoint, which included a sustained 30% or greater decline in eGFR, sustained eGFR below 15, chronic dialysis, kidney transplant, or death. Barratt said no atacicept-treated patient developed dialysis-dependent kidney failure, required a kidney transplant, or died during the study.
Vera and the FDA agreed to shift the study’s primary kidney-function assessment from week 104 to week 52 after results from an earlier Phase IIb study and concerns about continued placebo exposure, Barratt said. Participants are now transitioning to open-label atacicept for the remainder of the trial.
Proteinuria and Safety Findings
Atacicept treatment was associated with placebo-adjusted proteinuria reductions of 51% at week 52 and 60% at week 104. The company also reported reductions of 67% and 65%, respectively, in galactose-deficient IgA1, a pathogenic form of IgA. Hematuria resolved in 97% of atacicept-treated patients at week 104, according to the presentation.
Most adverse events were mild or moderate and resolved without treatment interruption or discontinuation, Barratt said. Injection-site reactions were also described as mild or moderate. The serious adverse-event rate was lower in the atacicept group than in the placebo group, and the company reported no clinically relevant hypogammaglobulinemia, opportunistic infections, or deaths in the atacicept group.
Although anti-drug antibodies were observed, Barratt said they did not have a clinically meaningful effect on pharmacokinetics, pharmacodynamics, safety, or efficacy in ORIGIN.
Commercial and Regulatory Plans
Chief Executive Officer Marshall Fordyce said TRUTAKNA received accelerated approval on July 7 and is being launched commercially in the United States. Vera plans to provide a commercial update alongside its third-quarter earnings release in November.
Fordyce said the company has started preparing a supplemental biologics license application to be submitted during the current quarter. Vera expects FDA review to potentially lead to full approval and an updated label in mid-2027. Barratt separately said a U.S. FDA submission supporting potential full approval is expected in 2027, with additional regional regulatory submissions planned afterward.
Fordyce said the company expects the ability to actively promote the full efficacy dataset after a potential full-approval label update. Chief Commercial Officer Matt Skelton said he expects “a nice inflection point” once the company can promote the comprehensive dataset.
Broader Treatment Discussion
During the question-and-answer session, Barratt said ORIGIN enrolled what he characterized as one of the highest-risk IgA nephropathy populations studied in a Phase III trial. He cautioned against direct comparisons with other studies because of differences in patient populations, follow-up duration, and composite endpoint definitions.
Barratt also said treatment approaches are shifting toward simultaneous management of disease biology and chronic kidney disease factors rather than a prolonged observation period following use of supportive therapies. He argued that treatment decisions should not rely solely on residual proteinuria, citing the kidney-function findings observed with atacicept.
Vera said it also presented data at Kidney Week involving adolescents with IgA nephropathy and planned to present initial data for atacicept in membranous nephropathy, another autoantibody-driven kidney disease.
About Vera Therapeutics (NASDAQ:VERA)
Vera Therapeutics, Inc is a clinical-stage biotechnology company focused on developing treatments for immunological diseases. The company’s research is centered on therapies that target the underlying causes of autoimmune conditions rather than primarily addressing their symptoms.
Vera’s lead product candidate is atacicept, a biologic designed to inhibit the B-cell survival factors BLyS and APRIL. The company has been evaluating atacicept in IgA nephropathy, an autoimmune kidney disease that can lead to progressive loss of kidney function, and has also investigated its potential in other immune-mediated diseases.
