Roche’s sefaxersen reduces proteinuria in phase III IMAgINATION trial

Phase III interim results

Prespecified interim analysis from the phase III IMAgINATION study showed that sefaxersen achieved statistically significant and clinically meaningful reductions in proteinuria versus placebo at 37 weeks, measured by 24‑hour urine protein‑to‑creatinine ratio (UPCR). The safety and tolerability profile was consistent with prior trials and no new safety signals were identified.

Mechanism and dosing

Sefaxersen is a liver‑directed antisense oligonucleotide that inhibits production of complement factor B, targeting the alternative complement pathway implicated in IgA nephropathy (IgAN). It is administered once monthly by subcutaneous injection and is designed for self‑administration; earlier phase I/II data showed reductions in proteinuria and plasma factor B and general tolerability.

Study design and next steps

IMAgINATION is a global, randomised, double‑blind, placebo‑controlled phase III study that enrolled 459 participants randomised 1:1 to sefaxersen or placebo for 105 weeks. The primary endpoint was change in UPCR at 37 weeks; the blinded study will continue to assess change in estimated glomerular filtration rate (eGFR) at week 105. Interim data will be presented at an upcoming medical congress and shared with health authorities.

Disease context

IgAN is a chronic autoimmune kidney disease typically diagnosed in young adults; up to 50% of patients progress to end‑stage kidney disease within 20 years. Proteinuria is a key surrogate for kidney damage and its reduction is associated with preservation of long‑term kidney function. Updated KDIGO guidance highlights the need to address both immune drivers and downstream kidney injury in IgAN.