Vera Therapeutics (VERA) Study Result summary

Study background and design

• ORIGIN Phase IIb was a multinational, randomized, placebo-controlled trial evaluating atacicept in high-risk adults with IgA nephropathy, using weekly subcutaneous injections and including an open-label extension up to 96 weeks.

• Participants had biopsy-proven IgAN, persistent proteinuria despite optimized standard of care, and eGFR ≥30 mL/min/1.73m²; about 25% were on SGLT2 inhibitors at baseline, and use of RAASI was allowed.

• The primary endpoint was change in urine protein-to-creatinine ratio (UPCR) at week 24, with secondary endpoints including UPCR at week 36, eGFR change up to week 96, and hematuria resolution.

• 116 participants were randomized, with over 90% completing atacicept treatment through 96 weeks.

• Atacicept is a dual inhibitor of BAFF and APRIL, targeting B-cell activation central to IgAN pathology.

Efficacy results

• Atacicept led to sustained and substantial reductions in Gd-IgA1, proteinuria (mean -66% at 96 weeks), and hematuria, with significant improvements as early as week 36.

• Hematuria resolved in a majority of participants, and Gd-IgA1 levels decreased by up to 64%.

• The annualized eGFR decline was 0.6 mL/min/1.73m² per year, closely matching healthy individuals and far outperforming other therapies.

• The eGFR profile contrasts with the typical decline seen in IgAN, suggesting disease modification and potential to prevent kidney failure.

• Atacicept provides the longest duration data for a B-cell modulator in IgAN to date.

Safety and tolerability

• Atacicept was well-tolerated over 96 weeks, with a favorable safety profile and over 90% patient retention.

• Most treatment-emergent adverse events were mild to moderate, with injection site reactions being the most common drug-related events.

• Serious TEAEs were infrequent and included isolated cases such as pneumonia and acute kidney injury; no deaths were reported.

• Infection rates, including during the COVID era, were similar between atacicept and placebo groups, and patients maintained robust vaccine responses.

• No significant hypogammaglobulinemia or concerning safety signals emerged over two years of treatment.