Roche's sefaxersen, a liver-directed antisense oligonucleotide (ASO) targeting complement factor B, met its primary endpoint in a Phase III trial in IgA nephropathy (IgAN), reporting statistically significant and clinically meaningful reductions in proteinuria versus placebo at 37 weeks. Roche and its licensing partner Ionis Pharmaceuticals (Nasdaq: IONS) said the interim data will be shared with health authorities and presented at an upcoming medical congress, signaling a potential path toward regulatory submission.
Sefaxersen works by binding to complement factor B mRNA in hepatocytes, triggering its degradation and reducing hepatic synthesis of factor B, thereby suppressing the alternative complement pathway — a key driver of glomerular inflammation and kidney damage in IgAN. The once-monthly subcutaneous formulation is designed for self-administration.
The IMAgINATION study enrolled 459 adults with primary IgAN at high risk of progression, randomized 1:1 to sefaxersen or placebo for 105 weeks. The prespecified interim analysis at 37 weeks measured change from baseline in 24-hour urine protein-to-creatinine ratio (UPCR). Roche described the improvement as statistically significant and clinically meaningful but did not disclose numerical values; detailed efficacy data are reserved for the medical congress presentation. The safety profile was consistent with previously reported data, with no new safety signals identified. The study remains blinded and continues to assess change in eGFR at week 105.
The IgAN treatment landscape has expanded substantially since 2021, with six FDA-approved therapies now available, spanning oral agents — budesonide (Tarpeyo), sparsentan (Filspari), iptacopan (Fabhalta), and atrasentan (Vanrafia) — and subcutaneous biologics sibeprenlimab (Voyxact) and atacicept-vymj (Trutakna). Sefaxersen's most direct mechanistic overlap is with Novartis' Fabhalta, an oral small molecule that also inhibits factor B of the alternative complement pathway; sefaxersen reduces factor B at the mRNA level via monthly subcutaneous injection, a different modality and dosing schedule. Vertex Pharmaceuticals' dual APRIL/BAFF blocker povetacicept has a BLA accepted by the FDA with a PDUFA date of November 30, 2026.