CARLSBAD, Calif. — October 23, 2026
Ionis Pharmaceuticals announced new Phase 3 data from its partner Roche showing that investigational sefaxersen significantly reduced proteinuria in adults with primary immunoglobulin A nephropathy (IgAN). Results from the ongoing IMAgINATION study, presented during a late-breaking oral session at the 2026 American Society of Nephrology (ASN) Kidney Week meeting, demonstrated a 43.1% reduction in proteinuria relative to placebo at Week 37. The treatment effect was statistically significant, with a 95% confidence interval of 32.5%–52.0% and a P value below 0.0001. Proteinuria, measured using the 24-hour urine protein-to-creatinine ratio (UPCR), is a key indicator of kidney damage, and reductions in urinary protein levels are associated with the preservation of long-term kidney function. The findings also showed consistent treatment effects across all prespecified patient subgroups. Among participants who had hematuria, or blood in the urine, at baseline, a greater proportion achieved hematuria resolution by Week 37 with sefaxersen than with placebo. Sefaxersen is an investigational, liver-directed antisense oligonucleotide (ASO) designed to inhibit production of complement factor B, a protein involved in the alternative complement pathway that contributes to inflammation in IgAN. The therapy is intended to be administered as a once-monthly subcutaneous injection, with a design intended to support convenient self-administration at home. The treatment was well tolerated in the Phase 3 study, with a safety profile consistent with previously reported Phase 2 findings and no new safety signals. The trial will continue to assess kidney function over the longer term, with estimated glomerular filtration rate (eGFR) evaluated at Week 105. Although the interim results demonstrate a significant reduction in proteinuria, additional follow-up will be important to determine whether this effect translates into sustained preservation of kidney function.
Sefaxersen Targets Complement Factor B Production
Sefaxersen is being developed as a targeted RNA-based treatment for IgA nephropathy, a chronic kidney disease driven by immune processes and inflammation. In people with IgAN, immune complexes containing immunoglobulin A accumulate in the kidneys and activate the alternative complement pathway. This process contributes to inflammation and damage in the glomeruli, the tiny filtering structures within the kidneys. Complement factor B is a component of this pathway, and its levels are elevated in people with IgAN. Sefaxersen is designed to reduce factor B production in the liver, potentially providing sustained control of alternative complement pathway activity. As an antisense oligonucleotide, it targets RNA involved in protein production rather than directly binding to the circulating protein. Ionis describes sefaxersen as the first RNA-targeted therapy being evaluated for IgAN and a highly specific, liver-directed inhibitor of factor B production. Its development reflects efforts to address underlying disease mechanisms rather than focusing exclusively on downstream manifestations such as proteinuria and elevated blood pressure. In the Phase 3 IMAgINATION study, the 43.1% relative reduction in proteinuria compared with placebo met the primary endpoint at Week 37. The reported effect was consistent across the prespecified subgroups, supporting the potential applicability of the findings across the populations examined. The hematuria findings provide an additional measure of response, although the supplied interim announcement does not specify the exact proportions of patients achieving resolution. Ionis Chief Executive Officer Brett P. Monia, Ph.D., said the results support the company’s belief that sefaxersen could become an important treatment option for people living with IgAN. He highlighted its proteinuria reduction and potential to help reduce the need for long-term dialysis or kidney transplantation. These potential long-term benefits have not yet been established by the interim results. Roche licensed sefaxersen from Ionis for the treatment of complement-mediated diseases. Under their agreement, Ionis received an upfront payment, a license fee and development milestone payments, and remains eligible for additional regulatory and sales milestone payments and tiered royalties on net sales.
IMAgINATION Phase 3 Study Continues Long-Term Evaluation
The IMAgINATION study (NCT05797610) is a multicenter, randomized, double-blind, placebo-controlled Phase 3 trial evaluating the efficacy and safety of subcutaneous sefaxersen in people with primary IgAN who are at high risk of disease progression. The study enrolled 459 participants, randomized in a 1:1 ratio to receive sefaxersen or placebo for 105 weeks. Participants receive treatment alongside optimized standard of care. The primary endpoint measures change from baseline in UPCR at Week 37, while the ongoing blinded study will assess longer-term kidney function using eGFR at Week 105. The interim results showed a statistically significant proteinuria reduction, with a 95% confidence interval of 32.5%–52.0% and a P value below 0.0001. The study also reported a higher proportion of hematuria resolution among participants receiving sefaxersen compared with placebo. No new safety signals were identified, and tolerability was consistent with the previously reported Phase 2 experience. The continued study is designed to provide further evidence on whether the treatment’s effect on urinary protein is accompanied by a favorable trajectory in kidney function over time. Participants may switch to open-label treatment after Week 105 at the investigator’s discretion or after the common-close time point, whichever occurs first. Roche intends to share the data with health authorities as development progresses. The treatment’s monthly subcutaneous dosing and intended home administration may offer practical advantages for patients who require long-term disease management. Nevertheless, regulatory status, the final benefit-risk assessment and the potential role of sefaxersen in clinical practice will depend on additional clinical evidence and health-authority review.
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Ionis and Roche Address Unmet Needs in Kidney Disease
IgAN, also known as Berger’s disease, is a chronic and progressive autoimmune kidney disease that is commonly diagnosed before age 40. It is a leading cause of primary glomerulonephritis and can progress to end-stage kidney disease. The companies report that up to 50% of patients may develop end-stage kidney disease within 20 years of diagnosis, highlighting the need for therapies that can preserve kidney function over the long term. Current management strategies often focus on reducing proteinuria and controlling blood pressure, while updated Kidney Disease: Improving Global Outcomes (KDIGO) guidance emphasizes addressing both the underlying immune-mediated causes and the consequences of kidney damage. Despite advances in treatment, some patients remain at risk of progression and require additional targeted options. Sefaxersen is intended to address this need by inhibiting complement factor B production through an RNA-targeted mechanism. Ionis has spent more than three decades developing RNA-targeted medicines and maintains a pipeline in neurology, cardiometabolic disease and other areas of significant unmet medical need, alongside marketed medicines and research into gene-editing approaches. Roche’s development partnership brings sefaxersen into a broader clinical program focused on complement-mediated disease. The Phase 3 IMAgINATION findings provide evidence of a significant reduction in proteinuria over 37 weeks and a safety profile consistent with earlier studies. The trial’s planned eGFR assessment at Week 105 will be important in determining whether these interim improvements are accompanied by sustained kidney-function benefits. Sefaxersen remains investigational, and further results and regulatory review are needed before its potential availability to patients can be determined.
Source:Ionis Pharmaceuticals,Press release
