Roche's IgAN hopeful sefaxersen passes phase 3 test
Roche has staked a claim to the increasingly crowded IgA nephropathy (IgAN) category, which has seen half a dozen new therapies approved by the FDA in the last decade, with plenty more in late-stage development.
The Swiss pharma group has just reported topline results from the phase 3 IMAgINATION study of Factor B inhibitor sefaxersen (formerly IONIS-FB-LRx) in IgAN, a progressive kidney disease that generally emerges in young adults and can ultimately lead to kidney failure requiring dialysis and transplantation.
Roche, which licenses the antisense drug from Ionis, said the study met its primary endpoint with "statistically significant and clinically meaningful" reductions in proteinuria – a marker for kidney damage – with sefaxersen compared to placebo after 37 weeks of treatment.
Ionis and Roche reckon that sefaxersen's once-monthly administration by subcutaneous injection opens up the potential for at-home self-administration by patients and could help it compete with the current armamentarium of IgAN therapies.
A couple of IgAN medicines can be delivered subcutaneously, including Otsuka's APRIL inhibitor Voyxact (sibeprenlimab) and Vera Therapeutics' dual BAFF and APRIL inhibitor Trutakna (atacicept). Of these, Voyxact can be self-administered once a month, like Roche and Ionis' candidate, while Trutakna is dosed with an autoinjector once a week. Meanwhile, Novartis has an oral Factor B inhibitor Fabhalta (iptacopan) dosed twice-daily.
"Sefaxersen may […] offer a new treatment option to help slow disease progression and potentially reduce the long-term need for dialysis or kidney transplantation," said Levi Garraway, Roche's chief medical officer.
That sentiment was shared by Bonnie Schneider, director and co-founder of the US-based IgA Nephropathy Foundation, who said the positive results from the IMAgINATION study "give us hope that emerging therapies could help preserve kidney function and transform the treatment landscape."
The IMAgINATION study will continue as a blinded study to evaluate the change in kidney function over two years, as measured by estimated glomerular filtration rate (eGFR). Roche said it will share its interim analysis with health authorities to see if it could support regulatory filings.
Other IgAN candidates in late-stage clinical testing include Novartis' anti-APRIL antibody zigakibart, Takeda's anti-CD38 drug mezagitamab, AstraZeneca's complement C5 inhibitor Ultomiris (ravulizumab), Vertex Pharma's recently filed BAFF/APIL antagonist povetacicept, and Biogen's anti-CD38 antibody felzartamab.
Roche licensed rights to sefaxersen in 2022, paying Ionis $55 million, having taken an option on the drug in a deal worth up to $760 million in 2018, when its primary indication was eye disorder age-related macular degeneration (AMD) – an indication that was dropped in 2024.
