Roche Phase III data show sefaxersen cut proteinuria 43% in IgAN
Roche has presented interim Phase III data showing its investigational antisense oligonucleotide (ASO) sefaxersen achieved a statistically significant 43.1% reduction in proteinuria relative to placebo at 37 weeks in adults with primary IgA nephropathy (IgAN), meeting the primary endpoint of the IMAgINATION study. The 95% confidence interval ran from 32.5% to 52.0%, with a p-value below 0.0001. Results were presented as a late-breaking oral at ASN Kidney Week 2026 in Denver.
The 459-patient trial, which randomises participants 1:1 to sefaxersen or placebo on top of optimised standard of care, also showed a higher rate of haematuria resolution at week 37 among sefaxersen-treated patients who had blood in the urine at baseline. The treatment effect was consistent across all prespecified subgroups. Roche said the safety profile aligned with the earlier Phase II study, with no new signals emerging.
How sefaxersen works
Sefaxersen is designed as a once-monthly subcutaneous injection intended for self-administration. It acts in the liver to inhibit production of complement factor B, a protein elevated in IgAN patients, thereby suppressing the alternative complement pathway that drives kidney inflammation and glomerular damage. Roche licensed the asset from Ionis Pharmaceuticals, the US ASO specialist whose platform underpins several approved medicines including inclisiran and eplontersen.
Levi Garraway, Roche's Chief Medical Officer and Head of Global Product Development, said the results demonstrated sefaxersen's "potential to meaningfully reduce protein in the urine" and that, by targeting complement factor B in the liver, it "may offer a novel approach to slow disease progression in IgAN, potentially helping patients delay or avoid long-term dialysis or kidney transplantation."
The IMAgINATION study will continue blinded to assess eGFR change at week 105, the principal long-term kidney-function readout. Roche said data would be shared with health authorities with the aim of advancing the programme to regulatory submission.
Market context and competitive landscape
IgAN affects at least 25 adults per million worldwide annually and is typically diagnosed before the age of 40. Up to half of patients reach end-stage kidney disease within 20 years of diagnosis, making it one of the more consequential primary glomerular diseases in terms of population burden. The updated KDIGO 2025 guidelines explicitly call for therapies that address both the underlying immune-mediated cause and downstream kidney damage, framing the unmet need sefaxersen is positioned to fill.
The IgAN competitive landscape has changed rapidly. Sparsentan received accelerated approval from the FDA in 2023, and the selective endothelin and angiotensin receptor antagonist budesonide formulation Nefecon is now approved in both the US and EU. Most recently, iptacopan, a factor B inhibitor from Novartis administered orally twice daily, received FDA approval in 2024, making it a direct mechanistic comparator to sefaxersen. Roche's ASO approach differentiates through its once-monthly subcutaneous dosing and liver-directed mechanism, though head-to-head data against iptacopan do not exist, and physicians will weigh the convenience of oral dosing against self-injection in practice. The full two-year eGFR dataset, expected from IMAgINATION at week 105, will be central to any reimbursement argument given that proteinuria reduction, while accepted as a surrogate endpoint, is not universally accepted as a stand-alone basis for full approval in all jurisdictions.