Why it matters: The missing number makes it difficult to assess Roche’s claim that the drug has “best-in-class potential” in an IgAN field where several competitors have already produced placebo-adjusted proteinuria reductions of around 40%-50%.
- The prespecified interim analysis of the 459-patient IMAgINATION trial met its primary endpoint at week 37, with sefaxersen producing a statistically significant and clinically meaningful reduction in 24-hour urine protein-to-creatinine ratio (UPCR) versus placebo. Roche said there were no new safety signals.
How it works: Sefaxersen is a liver-directed antisense oligonucleotide designed to reduce production of factor B. Roche licensed the drug from Ionis and is developing it as a once-monthly subcutaneous injection that patients could self-administer.
The catch: Roche did not disclose the magnitude of the reduction.
- That matters because the efficacy bar in IgAN has risen quickly. Otsuka’s APRIL inhibitor sibeprenlimab reduced UPCR by 51.2% versus placebo at nine months in Phase 3, while Vertex’s BAFF/APRIL inhibitor povetacicept achieved a 49.8% placebo-adjusted reduction at week 36. Vera Therapeutics’ atacicept delivered a 41.8% between-group reduction at week 36.
Zoom in: The closest comparison is Novartis’ iptacopan. Like sefaxersen, it targets complement factor B, although through a different mechanism. Iptacopan reduced proteinuria by 38.3% versus placebo at nine months and has since shown significantly slower loss of kidney function over two years.
What’s next: IMAgINATION remains blinded and will continue to week 105, when Roche will assess whether the proteinuria benefit translates into preservation of kidney function measured by eGFR. The company plans to present the interim data at an upcoming medical meeting and share them with health authorities.
Bottom line: Until those numbers are released, Roche has shown that sefaxersen works on the surrogate endpoint, but not yet how it stacks up against an increasingly competitive IgAN field.
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