Roche reports sefaxersen cut proteinuria 43.1% in Phase 3 IgAN trial

Ionis Pharmaceuticals (Nasdaq: IONS) disclosed that partner Roche presented late-breaking Phase 3 data showing sefaxersen achieved a statistically significant 43.1% reduction in proteinuria relative to placebo at 37 weeks in patients with IgA nephropathy. The results, presented at the American Society of Nephrology Kidney Week 2026, come from the IMAgINATION study, which is evaluating the antisense oligonucleotide in adults with primary IgA nephropathy who are receiving optimized standard of care.

Proteinuria, measured by the 24-hour urine protein-to-creatinine ratio, is a key indicator of kidney damage. The study reported a 95% confidence interval of 32.5 to 52.0 for the reduction, with a p-value of less than 0.0001. The data indicated that treatment effects were consistent across all prespecified patient subgroups. Among patients with baseline hematuria, a greater proportion achieved hematuria resolution at Week 37 with sefaxersen compared to placebo.

Sefaxersen is designed as a once-monthly subcutaneous injection for self-administration at home. The drug inhibits the production of complement factor B, a protein that is elevated in people with IgA nephropathy. By providing sustained control of the alternative complement pathway, sefaxersen aims to reduce kidney inflammation and slow disease progression. The Phase 3 trial reported that sefaxersen was well tolerated, with a safety profile consistent with previous Phase 2 findings and no new safety signals.

Ionis Pharmaceuticals (Nasdaq: IONS), which licensed sefaxersen to Roche for the treatment of complement-mediated diseases, highlighted the data in an 8-K filing. Brett P. Monia, Ph.D., chief executive officer of Ionis, stated that the results support the belief that sefaxersen is uniquely positioned to treat IgA nephropathy and offer the potential to help reduce the need for long-term dialysis or kidney transplantation.

The IMAgINATION study enrolled 459 people who were randomized 1:1 to receive either sefaxersen or placebo for 105 weeks. The primary endpoint was the change from baseline in the urine protein-to-creatinine ratio at 37 weeks. The trial will continue as a blinded study to evaluate changes in kidney function over two years, measured by estimated glomerular filtration rate at week 105. After week 105 or the common-close timepoint, whichever occurs first, investigators may allow participants to switch to open-label treatment.

Roche stated it will share data with health authorities with the goal of bringing the treatment to patients as soon as possible. IgA nephropathy, also known as Berger’s disease, is a chronic and progressive autoimmune condition that affects at least 25 adults per million worldwide each year. It is typically diagnosed before age 40 and can lead to end-stage kidney disease in up to 50% of patients within 20 years of diagnosis.