Sefaxersen cut proteinuria by 43.1% against placebo at 37 weeks in a Phase 3 trial in IgA nephropathy, according to data Ionis Pharmaceuticals Inc. (IONS) released on October 23.

Roche Holding AG, which licensed the drug from Ionis, announced the figures, which came from a late-breaking oral presentation at the American Society of Nephrology's Kidney Week 2026. Ionis filed its release with an 8-K the same day.

The number fills a gap. When Roche said on September 23 that the IMAgINATION study had met its primary endpoint at an interim analysis, it gave no size for the effect. It called the improvement statistically significant and clinically meaningful, and stopped there.

What the 43.1% reduction measures

The primary endpoint is the change from baseline in the 24-hour urine protein-to-creatinine ratio at week 37. Protein leaking into urine is a key marker of kidney damage. Ionis said a fall in this ratio tracks closely with kidneys holding their function over the long run.

• Proteinuria reduction versus placebo: 43.1%.
• 95% confidence interval: 32.5% to 52.0%.
• P value: below 0.0001.
• Patients enrolled: 459, randomized one to one.
• Planned treatment period: 105 weeks.

Ionis said the effect held across all prespecified subgroups. Among patients who had blood in their urine at the start, more on sefaxersen than on placebo saw it clear by week 37. The release gave no percentages for that measure, and it reported no new safety signals.

How the drug works and how Ionis gets paid

Sefaxersen is an antisense oligonucleotide directed at the liver. It blocks production of complement factor B, a protein that Ionis said is elevated in people with IgA nephropathy. The drug is designed as a once-monthly injection that patients give themselves at home.

"These data support our belief that sefaxersen is uniquely positioned to treat IgA nephropathy," Ionis chief executive Brett Monia said in the release.

Roche holds the license. Ionis has already received an upfront payment, a license fee and development milestones, and it is eligible for regulatory and sales milestones plus tiered royalties on net sales. Neither company has disclosed the dollar amounts.

The open question is kidney function at two years

The study stays blinded until week 105, when it measures kidney function through estimated glomerular filtration rate. Roche said it will share the data with health authorities. Neither Roche nor Ionis has put a date on a regulatory filing.