Vera Therapeutics (VERA) Study update summary

Trial design and rationale

• Atacicept blocks BAFF and APRIL, targeting B-cell and plasma-cell activity linked to pathogenic IgA production and immune-complex injury in IgA nephropathy.

• ORIGIN 3 randomized 428 high-risk adults to weekly 150 mg subcutaneous TRUTAKNA or placebo; participants were at risk of progression despite optimized supportive care.

• Baseline disease was high risk: mean eGFR ~65 mL/min, proteinuria 2.2 g/day, near-universal renin-angiotensin system inhibitor use, and 60%-65% SGLT2 inhibitor use.

• With FDA agreement, the eGFR endpoint moved from week 104 to week 52 to limit placebo exposure; annualized eGFR slope used data through week 104.

Efficacy and kidney outcomes

• At week 52, mean eGFR change was -0.1 vs -5.7 mL/min/1.73 m² with placebo (difference 5.6; 95% CI 3.7–7.5; p<0.0001).

• At week 104, mean eGFR change was -1.8 vs -12.8 mL/min/1.73 m² (difference 11.1; 95% CI 7.7–14.4; nominal p<0.0001).

• Annualized eGFR slope through week 104 was -0.6 vs -5.6 mL/min/1.73 m²/year (difference 5.0; 95% CI 3.6–6.5; p<0.0001); treated patients lost less than 1 mL/min/year.

• Through week 104, composite kidney progression risk fell 76% (HR 0.24; 95% CI 0.12–0.48; p<0.0001); all composite events first involved sustained ≥30% eGFR decline.

• Placebo-adjusted UPCR reductions were 51% at week 52 and 60% at week 104; Gd-IgA1 reductions were 67% and 65%, respectively, and hematuria resolved in 97% of treated patients at week 104.

Safety and follow-up

• Serious adverse events occurred in 7% with TRUTAKNA vs 15% with placebo; adverse events leading to discontinuation occurred in 2% vs 10%.

• Infections occurred in 51.4% vs 52.3%; serious or severe infections in 3% vs 4%. No opportunistic infections or clinically relevant hypogammaglobulinemia were reported; no deaths occurred in the TRUTAKNA group.

• ORIGIN 3 participants are transitioning to open-label atacicept, with follow-up through week 156; longer-term monitoring is planned.