Genentech's sefaxersen reduces proteinuria in Phase III IgAN interim analysis

Phase III interim results

At a prespecified interim analysis of the Phase III IMAgINATION study, sefaxersen met the primary endpoint, delivering statistically significant and clinically meaningful reductions in proteinuria versus placebo at 37 weeks as measured by 24‑hour urine protein‑to‑creatinine ratio (UPCR). The safety and tolerability profile was consistent with prior data and no new safety signals were identified.

Mechanism and dosing

Sefaxersen is a liver‑directed antisense oligonucleotide given as a once‑monthly subcutaneous injection designed to inhibit production of complement factor B, thereby reducing activity of the alternative complement pathway and lowering serum factor B and proteinuria.

Study design and next steps

IMAgINATION is a multicenter, randomized, double‑blind, placebo‑controlled Phase III trial that enrolled 459 people with primary IgAN at high risk of progression, randomized 1:1 to sefaxersen or placebo for 105 weeks. The trial will continue blinded to evaluate change in kidney function (eGFR) at week 105; interim data will be presented at a medical congress and shared with health authorities.

Clinical context

IgA nephropathy is a chronic autoimmune glomerulonephritis typically diagnosed before age 40 and can lead to end‑stage kidney disease in up to 50% of patients within 20 years; reductions in proteinuria are strongly associated with preservation of long‑term kidney function.