Ionis Pharmaceuticals' Phase 3 kidney trial meets proteinuria endpoint
Sefaxersen beat placebo on a week-37 urine protein measure, but Roche and Ionis have not disclosed the size of the effect or safety rates.
Adrian Kessler· Sep 23, 2026
Urine protein fell more on sefaxersen than on placebo at week 37, as Ionis Pharmaceuticals, Inc. NASDAQIONS said Wednesday that its partner's Phase 3 IMAgINATION trial met its primary endpoint in IgA nephropathy. The 459-person study remains blinded for a week-105 comparison of kidney function.
The Sept. 23 company release called the difference statistically significant and clinically meaningful. It gave neither group's change in urine protein, the p value or confidence interval, nor the number of patients in the interim analysis. The partners plan to present the data at a medical meeting and share them with health authorities, but named no meeting or filing date.
Ionis develops RNA-targeted medicines in California, with marketed drugs and a pipeline spanning neurological, cardiovascular and other diseases.
The announcement landed before Nasdaq's Wednesday regular session, leaving no share reaction to report at the time of the release. The iShares Biotechnology ETF NASDAQIBB closed at US$210.81 at 4 p.m. EDT on Sept. 22, before the readout.
The Size Of The Proteinuria Effect Is Still Undisclosed
Roche Holding AG SWXRO OTCMKTSRHHBY runs the study after licensing sefaxersen from Ionis. The partners say 459 adults were enrolled and randomly assigned 1:1 to sefaxersen or placebo. Roche's published study design specifies optimized supportive care, including an ACE inhibitor or angiotensin receptor blocker at the maximum tolerated dose.
The primary endpoint measures change in the urine protein-to-creatinine ratio from a 24-hour collection at week 37. The poster lists the slope of estimated glomerular filtration rate at week 105 as a secondary endpoint. That longer comparison remains blinded.
Roche scheduled injections on days 1, 15 and 29. Dosing then shifts to every four weeks. Its April 2024 study-design poster permits trained participants or caregivers to administer treatment at home or another suitable location only after the first eight doses. Sefaxersen lowers production of factor B in the liver, targeting a pathway involved in kidney inflammation.
The companies did not disclose adverse-event counts or rates by treatment arm, leaving the tolerability comparison for the fuller presentation.
"The safety and tolerability profile of sefaxersen was consistent with previously reported data, with no new safety signals identified," Ionis and Roche said in the Sept. 23 release.
The FDA's Nov. 25, 2025 decision on Voyxact shows how a similar urine-protein measure can support accelerated approval in IgA nephropathy, with longer-term kidney benefit still to be confirmed. Neither company disclosed FDA feedback on IMAgINATION's design or an application timetable for sefaxersen.
Approved Kidney Drugs Set The Comparison
Under the Roche licence, Ionis may receive regulatory and sales milestones and royalties if sefaxersen advances and sells. Ionis reported US$2.1 billion in cash and short-term investments at June 30 in its July 29 results filed with the SEC. Management still targeted cash-flow breakeven in 2028. Neither Sept. 23 release supplied a company cash-runway date.
The approved IgA nephropathy field already includes Novartis AG SWXNOVN NYSENVS, whose July 16 announcement said Fabhalta won traditional FDA approval after slowing kidney-function decline by 48 per cent against placebo over two years. Travere Therapeutics, Inc. NASDAQTVTX lists Filspari in its April 13 prescribing information as a treatment to slow kidney-function decline in adults with IgA nephropathy.
Sept. 23 regular U.S. trading is the first market test for Ionis shares after the readout. Roche has not dated the full interim presentation or a regulatory submission; its week-105 kidney-function comparison remains the trial's longer test.
