At 36 weeks, atacicept delivered a 46% reduction from baseline in 24-hour urine protein-to-creatinine ratio and a 42% reduction versus placebo (p<0.0001) in adults with IgA nephropathy. Secondary signals moved in the same direction, with a 68% decrease in Gd-IgA1 and hematuria resolution in 81% of participants who entered with hematuria. Safety appeared comparable to placebo across the program; in the ORIGIN 3 complete analysis set, serious adverse events were reported in 0.5% on atacicept versus 5% on placebo, with no deaths and no immunosuppression signal. The readout is from the ongoing, global, double-blind Phase 3 ORIGIN 3 trial, which randomized 431 patients 1:1 to weekly subcutaneous atacicept 150 mg or placebo. The analysis presented at Kidney Week and published in the New England Journal of Medicine reflects the pre-specified proteinuria endpoint at week 36, with consistent efficacy across age, sex, race, region, baseline proteinuria, baseline eGFR, and SGLT2 inhibitor use. The blinded study continues to assess kidney function over two years via eGFR, with completion expected in 2027. Vera plans a U.S. BLA in Q4 2025 seeking Accelerated Approval, positioning for a potential 2026 PDUFA. The company is also running an extension study and exploring additional autoimmune kidney indications. Strategically, this is a bid to establish a B-cell–directed backbone in IgA nephropathy, distinct from steroidal approaches and hemodynamic modifiers. Dual BAFF/APRIL inhibition targets autoantibody biology upstream, a different bet than endothelin or renin-angiotensin modulation, and a step beyond APRIL-only programs. The timing and design align with recent regulatory precedent that accepts proteinuria as a surrogate for accelerated pathways in IgAN, while reserving eGFR slope for conversion to traditional approval. The safety profile will be central to differentiation, as regulators and prescribers have grown cautious about chronic immunomodulation. Operationally, a once-weekly at-home injection simplifies delivery compared with infusion-based biologics and may lower site burden. For sites and CROs, the near-term lift shifts from intensive visit schedules to adherence, drug accountability, and lab logistics to sustain a blinded, two-year eGFR readout. Retention, centralized labs for proteinuria and eGFR monitoring, and management of background standard-of-care therapies will be critical as SGLT2 inhibitor uptake grows and practice patterns evolve. Sponsors and payers will scrutinize positioning relative to existing options such as targeted-release budesonide and endothelin antagonism, including sequencing and potential combinations for residual proteinuria. Regulators will home in on subgroup consistency, durability of the proteinuria effect, and confirmation of the eGFR slope to support label breadth. For patients, a non-steroidal, B-cell–modulating option with fewer serious adverse events could shift treatment dynamics, assuming long-term safety holds. The key unknown is the translation to kidney function: whether a robust proteinuria signal sustains and translates into a clinically meaningful eGFR benefit over 2 years. Competitive pressure is building from APRIL-only antibodies and other immune and complement-pathway assets, raising questions about class effects, safety differentials, and eventual combination logic. Execution risks include maintaining blinded conduct through 2027, avoiding background therapy drift, scaling manufacturing and cold-chain distribution for home use, and designing post-marketing commitments that satisfy regulators across regions. Near-term milestones to watch are FDA interactions around the Accelerated Approval package, any interim eGFR trends, and head-to-head or indirect comparative data that clarify where a dual BAFF/APRIL inhibitor fits in an increasingly crowded IgAN toolkit.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
