IgA nephropathy drug meets key phase 3 goal

Roche announced positive prespecified interim results from the phase 3 IMAgINATION trial, reporting that investigational sefaxersen met the study's primary endpoint by achieving statistically significant and clinically meaningful reductions in proteinuria compared with placebo at 37 weeks, as measured by 24-hour urine protein-to-creatinine ratio (UPCR).

The findings are notable because proteinuria is a major indicator of kidney damage and an established surrogate marker associated with future kidney function decline. IgA nephropathy (IgAN) is a chronic autoimmune kidney disease that can progress to kidney failure in up to 50% of patients within 20 years of diagnosis. If ongoing data confirm preservation of kidney function, the therapy could emerge as a new option aimed at slowing disease progression and reducing the future need for dialysis or transplantation.

Sefaxersen is a liver-directed antisense oligonucleotide and the first mRNA-targeted therapy being developed for IgAN. It is designed to reduce production of complement factor B, a key component of the alternative complement pathway implicated in IgAN-related kidney injury. By targeting an upstream driver of disease, the therapy aims to address underlying disease mechanisms rather than primarily managing downstream consequences.

Sefaxersen is being developed as a once-monthly subcutaneous injection that patients can self-administer at home. Roche reported that the safety and tolerability profile was consistent with previous studies, with no new safety signals identified during the interim analysis.

While the current results focus on proteinuria reduction, the study remains ongoing and blinded. Investigators are continuing to evaluate whether these early benefits translate into preservation of kidney function, with changes in estimated glomerular filtration rate (eGFR) at 105 weeks serving as a key long-term outcome measure.

Detailed data are expected to be presented at a forthcoming medical meeting and shared with regulatory authorities. If longer-term kidney function benefits are confirmed, sefaxersen could become an important addition to the evolving treatment landscape for IgAN.

Source: Roche. (2026 Sep 22). Positive interim data shows Roche's sefaxersen significantly reduces proteinuria in people with IgA nephropathy (IgAN)