Vera's Trutakna Stabilizes eGFR and Cuts IgAN Progression Risk 76% in Final ORIGIN 3 Analysis
核心洞察
Vera Therapeutics reported that Trutakna (搜索) met all prespecified endpoints in the final ORIGIN 3 analysis of 428 adults with primary IgA nephropathy (搜索) at risk of progression.
Annualized eGFR slope through 104 weeks was -0.6 mL/min/1.73m2/year with Trutakna (搜索) versus -5.6 with placebo, a 5.0 mL/min/1.73m2/year treatment effect (p<0.0001).
Composite kidney disease progression events occurred in 11 Trutakna (搜索) patients versus 38 on placebo, a 76% risk reduction (hazard ratio 0.24; 95% CI 0.12, 0.48).
Vera Therapeutics reported that TRUTAKNA (搜索) (atacicept-vymj (搜索)) met all prespecified endpoints in the final efficacy analysis of the Phase 3 ORIGIN 3 trial in adults with primary IgA nephropathy (搜索) (IgAN) at risk for disease progression, with topline results from the final analysis set of 428 patients showing stabilization of kidney function and a 76% reduction in the risk of composite kidney disease progression events through 104 weeks.
The company said the eGFR results align with the KDIGO treatment goal of reducing the rate of kidney function decline to the physiologic rate of less than 1 mL/min/1.73m2/year. TRUTAKNA (搜索) is the first and only FDA-approved BAFF (搜索) and APRIL (搜索) inhibitor, and Vera plans to submit a supplemental Biologics License Application to the FDA in the fourth quarter of 2026 for full approval, with potential full approval anticipated in 2027.
Kidney Function and Progression Endpoints
Mean eGFR change from baseline at 52 weeks was -0.1 mL/min/1.73m2 (95% CI -1.4, 1.2) with TRUTAKNA (搜索) versus -5.7 mL/min/1.73m2 (95% CI -7.0, -4.4) with placebo, a treatment effect of 5.6 mL/min/1.73m2 (95% CI 3.7, 7.5; p<0.0001).
The annualized eGFR slope through 104 weeks was -0.6 mL/min/1.73m2/year (95% CI -1.6, 0.4) with TRUTAKNA (搜索) compared with -5.6 mL/min/1.73m2/year (95% CI -6.6, -4.6) with placebo, a treatment effect of 5.0 mL/min/1.73m2/year (95% CI 3.6, 6.5; p<0.0001).
Composite kidney disease progression events through 104 weeks occurred in 11 patients in the TRUTAKNA (搜索) group versus 38 in the placebo group, corresponding to a hazard ratio of 0.24 (95% CI 0.12, 0.48) and a 76% risk reduction (p<0.0001). No patients receiving TRUTAKNA experienced dialysis lasting at least 30 days, kidney transplantation, or death through 104 weeks, compared with eight patients in the placebo group.
TRUTAKNA (搜索) also achieved statistically significant reductions in the hierarchically tested endpoints of proteinuria, galactose-deficient IgA1 (Gd-IgA1), and hematuria.
Safety Profile Comparable to Placebo
Vera reported that TRUTAKNA (搜索) was well tolerated with a favorable safety profile generally comparable to placebo, consistent with previous results from the ORIGIN program. Rates of overall adverse events and infections or infestations were similar between the TRUTAKNA and placebo groups, and there were no opportunistic infections or clinically relevant hypogammaglobulinemia.
In clinical trials, infections were reported in 32% of TRUTAKNA (搜索) patients compared with 28% of placebo patients. The most common adverse reactions (≥5%) in patients treated with TRUTAKNA and placebo, respectively, were infections (32% vs 28%) and local administration reactions (30% vs 5%). The most common infection was upper respiratory tract infection (12% vs 9%), and the most common local administration reactions were injection site reaction (19% vs 2%) and injection site erythema (6% vs 1%).
TRUTAKNA (搜索) is contraindicated in patients with serious hypersensitivity to atacicept-vymj (搜索) or any excipients of TRUTAKNA. Because it suppresses the immune system by reducing antibody production, it may increase the risk of infections; patients with chronic or recurring infections may have an increased risk of serious infection. Live vaccines are not recommended within 30 days prior to initiation or during treatment with TRUTAKNA, and age-appropriate immunizations should be completed before initiating treatment. The safety and effectiveness of TRUTAKNA in pediatric patients have not been established, and available data on use in pregnant women exposed during clinical trials are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes.
Mechanism and Administration
TRUTAKNA (搜索) is a B-cell activating factor (BAFF (搜索)) and A proliferation-inducing ligand (APRIL (搜索)) inhibitor, a soluble recombinant fusion protein containing the human transmembrane activator and calcium-modulating cyclophilin ligand interactor (TACI) receptor that binds to the cytokines BAFF and APRIL. BAFF and APRIL are key cytokines that activate B cells and drive IgAN pathophysiology; in IgAN, activated B cells produce both the antigen and associated antibodies that result in the production of damaging IgA immune complexes. The overlapping roles of BAFF and APRIL in activating B cells support the potential for TRUTAKNA as a disease-modifying therapy.
The therapy is self-administered as an at-home, small-volume (1 ml), 150 mg once-weekly autoinjector.
Regulatory Status and Investigator Commentary
TRUTAKNA (搜索) is currently approved under the FDA's accelerated approval pathway to reduce proteinuria in adults with primary IgAN at risk for disease progression. The indication is approved based on reduction of proteinuria, and it has not been established whether TRUTAKNA slows kidney function decline over the long term in patients with IgAN; continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory clinical trial. The drug was first FDA approved on July 7, 2026.
"The ORIGIN 3 final analysis, demonstrating a significant reduction in risk of composite kidney disease progression, true stabilization of eGFR, and a favorable safety profile through two years, marks a milestone in IgAN treatment," said Richard Lafayette, M.D., F.A.C.P., Professor of Medicine, Nephrology and Director of the Glomerular Disease Center at Stanford University Medical Center, and a principal investigator for ORIGIN 3. "Prevention of kidney failure or kidney-related death is the ultimate goal. We now have evidence suggesting that TRUTAKNA (搜索) may help patients avoid dialysis, transplantation, or kidney-related death over the long term."
"We believe that upstream inhibition of BAFF (搜索) and APRIL (搜索) with TRUTAKNA (搜索) achieves results that reflect the potential for comprehensive disease modification in IgAN. ORIGIN 3 is the first reported Phase 3 IgAN trial to reach alignment with the FDA on an earlier final efficacy analysis, offering patients randomized to placebo an earlier opportunity to transition to open-label TRUTAKNA," said Marshall Fordyce, M.D., Founder and CEO of Vera Therapeutics. "The final results support this alignment and we plan to submit the supplemental BLA in the fourth quarter of this year. We look forward to the potential full approval of TRUTAKNA in 2027."
Detailed results from the final efficacy analysis will be shared at an upcoming scientific congress.
Commercial Launch Momentum
Vera reported that more than 350 patient start forms were generated in the first ten weeks following launch. "We are seeing paid claims and are pleased with initial payer policies. The early momentum of the TRUTAKNA (搜索) launch is very encouraging," said Matt Skelton, Chief Commercial Officer of Vera Therapeutics.
The company also operates TRUTAKNA (搜索) TRU SUPPORT, a patient support program offering insurance coverage assistance, financial assistance options for eligible patients, and educational resources; eligible commercially insured patients may pay as little as $0 out of pocket through a copay assistance program.
Disease Burden in IgA Nephropathy
IgAN is a serious, progressive, immune-mediated kidney disease and a leading cause of chronic kidney disease and kidney failure worldwide. Approximately 2.5 adults per 100,000 worldwide are diagnosed with IgAN each year, most often between 30 and 40 years of age. Over time, IgAN can lead to irreversible kidney damage and may ultimately require dialysis or kidney transplantation, and at least 50% of patients may progress to kidney failure or death within 10 to 20 years of diagnosis.
Competitive Landscape
Other agents are advancing in the IgAN space. In the Phase III VISIONARY trial (NCT05248646), eGFR was stabilized with an annualized eGFR slope of 0.3 mL/min/1.73 m2/year with Voyxact compared with a 4.2 mL/min/1.73 m2/year reduction with placebo, meeting the study's key secondary endpoint. In February 2026, Novartis presented final data from its Phase III ALIGN trial of Vanrafia (atrasentan) in IgAN, showing a 2.39 mL/min/1.73m2 difference in eGFR change from baseline versus placebo at week 136, four weeks after ending treatment. In March 2026, Vertex announced it would seek approval of povetacicept, an engineered fusion protein and dual inhibitor of the BAFF (搜索) and APRIL (搜索) cytokines, after the Phase III RAINER trial (NCT06564142) met its primary endpoint. More established therapies include Calliditas Therapeutics' Tarpeyo (budesonide), which gained accelerated approval in 2021, and Travere Therapeutics' Filspari (sparsentan), which gained accelerated approval in 2023; the two drugs subsequently won full approvals in December 2023 and September 2024, respectively.