Swiss pharmaceutical company Roche announced on October 23, 2026, that its experimental medication sefaxersen reduced proteinuria by 43.1% compared to a placebo in adults with primary immunoglobulin A nephropathy (IgAN), a chronic autoimmune kidney condition. The interim data from the ongoing Phase 3 IMAgINATION study, presented during a late-breaking oral session at the American Society of Nephrology (ASN) Kidney Week 2026, met its primary endpoint after 37 weeks of treatment. For patients facing progressive kidney damage, the results indicate that targeting liver proteins to calm immune activity may help preserve renal health over time.

Key Findings from the IMAgINATION Study

The global, randomized, double-blind, placebo-controlled Phase 3 IMAgINATION trial evaluated sefaxersen in adults with primary IgAN who were at high risk of disease progression despite receiving optimized standard-of-care therapy. At week 37, researchers measured the 24-hour urine protein-to-creatinine ratio (UPCR), a standard measure used to track kidney damage. According to Roche and a regulatory filing from development partner Ionis Pharmaceuticals reproduced by Stock Titan, the 43.1% reduction relative to placebo carried a 95% confidence interval of 32.5% to 52.0% (P<0.0001).

Secondary medical coverage has varied slightly in how it characterizes the trial data. While some reports refer broadly to a 43.1% drop in urine protein, HCPLive and Roche emphasize that this figure represents a treatment effect relative to the placebo group rather than an absolute within-patient reduction. Reports also cite different population figures for the ongoing study: MarketChameleon notes a total enrollment of 459 participants, while Europe Says reports 438 patients in the primary analysis cohort. The interim announcement from the manufacturer does not reconcile those two denominators.

In addition to the primary proteinuria findings, investigators observed that among participants who entered the study with hematuria (blood in the urine), a greater proportion achieved resolution at week 37 when treated with sefaxersen compared to placebo. Company researchers noted via RTTNews that the protein-lowering effects remained consistent across all prespecified patient subgroups, though subgroup consistency does not guarantee a benefit for every individual patient. According to Fierce Biotech, the drug was well tolerated and showed no new safety signals, maintaining a safety profile consistent with an earlier Phase 2 trial.

Understanding IgA Nephropathy and Complement Factor B

IgA nephropathy, also known as Berger's disease, is a chronic, progressive autoimmune condition and the most common form of primary glomerulonephritis—inflammation of the tiny filtering structures inside the kidneys. Typically diagnosed before the age of 40, the condition affects at least 25 adults per million worldwide each year. In people with IgAN, immune deposits accumulate inside the kidney filters, allowing blood and protein to leak into the urine. Up to 50% of patients develop end-stage kidney disease within 20 years of diagnosis, eventually requiring long-term dialysis or a kidney transplant.

Sefaxersen (also known as RG-6299) is designed as a once-monthly subcutaneous injection that patients can self-administer. It is an antisense oligonucleotide (ASO) that specifically targets the liver to inhibit the production of complement factor B. People with IgAN typically have elevated serum levels of complement factor B, a protein that drives overactivity in the alternative complement pathway of the immune system. By reducing the production of this protein in the liver, the medication aims to calm inflammation inside the kidneys and slow down structural damage.

"These phase III results demonstrate the potential for sefaxersen to meaningfully reduce protein in the urine, a key indicator of kidney damage, in people with IgA nephropathy," said Levi Garraway, MD, PhD, Roche's Chief Medical Officer and Head of Global Product Development, in the company's announcement. "By inhibiting complement factor B in the liver, sefaxersen may offer a novel approach to slow disease progression in IgAN, potentially helping patients delay or avoid long-term dialysis or kidney transplantation."

What This Means for Patients and Next Steps

While reducing protein in the urine is strongly associated with preserving renal health, the week 37 proteinuria readout is an interim milestone rather than proof of a cure or confirmed long-term kidney preservation. To determine whether the drug slows the actual loss of kidney function over a longer period, the IMAgINATION study is continuing as a blinded trial. Researchers will evaluate the change in estimated glomerular filtration rate (eGFR)—a primary measure of how well the kidneys filter waste from the blood—at week 105.

Roche stated it will share the interim Phase 3 findings with global health authorities as it works toward regulatory submissions. Full assessment of the medication's risk-benefit profile will require complete trial datasets detailing specific adverse event rates, study discontinuations, and the two-year kidney function outcomes.

What did the interim study show regarding absolute UPCR changes and safety?

The initial announcement provided the 43.1% placebo-relative reduction in 24-hour UPCR at week 37, along with a 95% confidence interval of 32.5% to 52.0%. Detailed figures regarding baseline proteinuria levels, exact absolute UPCR reductions in each study arm, and specific adverse event percentages were not included in the initial release and await full publication of the dataset.

Will the study prove that sefaxersen prevents long-term kidney failure?

Proteinuria reduction is a widely recognized surrogate marker for slowing kidney disease, but confirming long-term preservation of kidney function requires further testing. The IMAgINATION trial remains ongoing and blinded to track patients' estimated glomerular filtration rate (eGFR) through week 105, which will provide direct evidence on how well the drug slows functional decline.

When could sefaxersen become available to patients?

Sefaxersen remains an investigational therapy and has not yet been approved by regulatory agencies such as the U.S. Food and Drug Administration. Roche plans to submit the interim week 37 proteinuria data to health authorities, while continuing to collect two-year eGFR data to support full regulatory evaluation.

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