Roche: sefaxersen cuts proteinuria 43.1% in phase III IgAN trial
- Sefaxersen produced a 43.1% reduction in 24‑hour UPCR versus placebo at 37 weeks (95% CI 32.5–52.0; P<0.0001).
- The phase III IMAgINATION study enrolled 459 adults randomised 1:1 to sefaxersen or placebo for 105 weeks; primary endpoint was UPCR change at 37 weeks.
- Sefaxersen is a liver‑directed antisense oligonucleotide that inhibits complement factor B and is administered once‑monthly by subcutaneous self‑injection.
- Treatment effects were consistent across prespecified subgroups; more patients with baseline haematuria achieved haematuria resolution at Week 37, and no new safety signals were observed.
Key results
In the phase III IMAgINATION study, investigational sefaxersen reduced proteinuria (24‑hour urine protein‑to‑creatinine ratio) by 43.1% versus placebo at Week 37 (95% CI 32.5–52.0; P<0.0001). Results presented at ASN Kidney Week 2026 also reported a higher proportion of haematuria resolution at Week 37 among patients with baseline haematuria. Treatment effects were consistent across all prespecified patient subgroups.
Safety
Sefaxersen was reported to be well tolerated with a safety profile consistent with prior phase II data and no new safety signals observed in the interim analysis.
Mechanism and administration
Sefaxersen is a liver‑directed antisense oligonucleotide that inhibits production of complement factor B to modulate the alternative complement pathway; it is designed for once‑monthly subcutaneous dosing to enable self‑administration.
Study design and next steps
IMAgINATION is a randomized, double‑blind, placebo‑controlled phase III trial of 459 patients (1:1 randomisation) planned for 105 weeks. The study will remain blinded to assess change in kidney function via eGFR at Week 105, and data will be shared with health authorities.
Source: Roche