Roche reports 43.1% reduction in urine protein in trial of experimental kidney drug
Key Facts
Roche announced on October 23, 2026, that its experimental drug sefaxersen reduced proteinuria by 43.1% compared with placebo at week 37, a statistically significant result from the ongoing Phase III IMAGINATION study. The trial is investigating primary immunoglobulin A nephropathy, known as IgAN, a disease that can lead to declining kidney function. The company’s announcement reported the trial’s primary outcome: the change in the urine protein-to-creatinine ratio after 37 weeks. Roche announced positive results from a prespecified interim analysis on September 23, but did not disclose the size of the effect at the time; the October update provided week 37 data. Roche licensed the drug from Ionis, and its October announcement did not mention a new agreement or disclose deal amounts.
The 95% confidence interval for the estimated reduction in proteinuria ranged from 32.5% to 52.0%, while the p-value was less than 0.0001, according to Roche’s statement. The study measured the indicator using the protein-to-creatinine ratio in a urine sample collected over 24 hours, the measurement method underlying the reported result. The 43.1% figure represents a relative reduction in proteinuria in the sefaxersen group compared with the placebo group, not an absolute decline of the same magnitude within the treatment group alone. The company described the result as statistically significant and said a reduction in this ratio is strongly associated with preserving kidney function over the long term. Kidney function itself remains under assessment in the trial, which is still blinded until the final measurement time point.
The IMAGINATION study enrolled 459 people and randomly assigned them in a 1:1 ratio to sefaxersen or placebo, with treatment planned for 105 weeks. Roche’s statement described the trial as multicenter, randomized, double-blind and placebo-controlled, with week 37 set as the primary endpoint for the change in the protein-to-creatinine ratio. In addition to the primary result, the company said a greater proportion of participants who had blood in their urine at baseline achieved resolution of hematuria by week 37 with sefaxersen than with placebo. The statement did not provide numerical rates for this secondary measure, but included it among the reported analysis results. Roche also said the treatment effect was consistent across all prespecified subgroups, no new safety signals emerged, and tolerability was consistent with what had been seen in the Phase II study.
Sefaxersen is an experimental antisense oligonucleotide drug designed to target the liver and inhibit the production of factor B in the complement system, according to Roche. The treatment was designed for once-monthly subcutaneous injection and self-administration, targeting a pathway associated with the disease investigated in the trial. IgA nephropathy affects at least 25 adults per million people annually worldwide, according to the company’s estimate. The disease may progress to end-stage kidney disease in up to 50% of patients within 20 years of diagnosis. In this context, the proteinuria result is an indicator measured by the study, while the treatment’s effect on kidney function remains part of ongoing follow-up.
The study is continuing, with blinding maintained to assess changes in kidney function through estimated glomerular filtration rate at week 105, Roche said, adding that it will share the data with health authorities. The official study registry estimates completion on March 31, 2029; this is an expected date, not an announced date for a regulatory decision on the drug. Under the licensing arrangements, Ionis is entitled to an upfront payment, license fees and development milestone payments, and may also receive payments upon achievement of regulatory and commercial milestones, as well as tiered royalties on net sales of sefaxersen. Ionis did not specify the amounts of these payments or royalties in its statement. The financial arrangement comes while the drug remains experimental and the trial continues to measure kidney function after the week 37 result.