Roche sefaxersen hits Phase III primary endpoint in IgA nephropathy
Roche has announced positive prespecified interim results from its Phase III IMAgINATION study of sefaxersen in adults with primary IgA nephropathy (IgAN), with the trial meeting its primary endpoint of a statistically significant and clinically meaningful reduction in proteinuria compared with placebo at 37 weeks.
The measurement used was 24-hour urine protein-to-creatinine ratio (UPCR), a validated surrogate endpoint whose improvement is strongly associated with long-term preservation of kidney function. Roche has not yet released the absolute UPCR reduction figure, stating that full interim data will be presented at an upcoming medical congress and shared with health authorities.
The drug and the study
Sefaxersen is an antisense oligonucleotide (ASO) that targets complement factor B messenger RNA in the liver, reducing circulating levels of factor B and thereby suppressing overactivation of the alternative complement pathway, a central mechanism in IgAN-related kidney damage. It is designed for once-monthly subcutaneous self-administration, a practical advantage over infused biologics in a predominantly younger adult patient population.
The IMAgINATION study enrolled 459 patients randomised 1:1 to sefaxersen or placebo for 105 weeks. The interim analysis covered the 37-week primary endpoint; the study will continue blinded to assess estimated glomerular filtration rate (eGFR) at week 105, the harder measure of kidney function that regulators and clinicians regard as the more definitive readout. Roche licensed sefaxersen from Ionis Pharmaceuticals as part of its broader push into complement-mediated diseases.
Levi Garraway, Roche's Chief Medical Officer and Head of Global Product Development, said the results show sefaxersen "may offer a new treatment option to help slow disease progression and potentially reduce the long-term need for dialysis or kidney transplantation."
Market and competitive context
The IgAN treatment landscape has become one of the more active areas of nephrology drug development in recent years. Sparsentan, a dual endothelin and angiotensin receptor antagonist from Travere Therapeutics, received accelerated FDA approval in 2023 based on proteinuria data and is now enrolled in its confirmatory eGFR trial. AstraZeneca's iptacopan, a factor B inhibitor taken orally, gained FDA approval in 2024 for complement-3-glomerulopathy and is under evaluation in IgAN. In addition, targeted-release budesonide and several anti-APRIL biologics are either approved or in late-stage development, making the competitive field unusually crowded for a rare kidney disease indication.
Roche is positioning sefaxersen as having "best-in-class potential," a claim the company grounds in its liver-directed ASO mechanism and the depth and durability of complement factor B suppression seen in Phase I and II data. Whether that differentiation holds against a field that now includes both oral and injectable factor B inhibitors will depend largely on the absolute magnitude of the UPCR reduction and, ultimately, on the eGFR trajectory at week 105.
Updated KDIGO 2025 guidelines for IgAN explicitly call for therapies that address underlying immune-mediated drivers of disease alongside downstream kidney damage, a framing that aligns with Roche's complement-suppression rationale. If the eGFR data at week 105 are consistent with the proteinuria signal, sefaxersen would be well placed for an accelerated regulatory submission in both the United States and Europe. The company said it intends to engage health authorities as soon as the interim data are formally presented.