Ionis and Roche Report Positive Phase 3 IgAN Results

Carlsbad, California, U.S., September 23, 2026

IMAgINATION Study Meets Primary Endpoint

The IMAgINATION Phase 3 study is a multicenter, randomized, double-blind, placebo-controlled clinical trial designed to evaluate the efficacy and safety of sefaxersen in patients with primary IgAN who are considered at high risk of disease progression. The study enrolled 459 participants, who were randomized in a 1:1 ratio to receive either sefaxersen or placebo. Participants are being followed for 105 weeks, with the longer-term study designed to evaluate changes in kidney function using estimated glomerular filtration rate (eGFR).

The primary endpoint was the change from baseline in urine protein-to-creatinine ratio at Week 37. Proteinuria is an important indicator of kidney damage in IgAN, and reductions in urinary protein are associated with preservation of long-term kidney function. Ionis and Roche reported that sefaxersen achieved the primary endpoint with statistically significant and clinically meaningful improvement compared with placebo. The companies did not disclose the numerical treatment effect in the initial announcement and said detailed interim findings will be presented at an upcoming medical congress and shared with health authorities.

Sefaxersen Targets Complement Factor B

Sefaxersen is an investigational, highly specific liver-directed antisense oligonucleotide designed to inhibit production of complement factor B. Factor B plays an important role in the alternative complement pathway, part of the immune system that can contribute to inflammation and tissue injury. In IgAN, immune complexes accumulate in the kidneys and activate complement pathways, contributing to inflammation and progressive kidney damage. By reducing factor B production, sefaxersen is intended to provide sustained control of alternative complement pathway activity.

The therapy is being evaluated as a once-monthly subcutaneous injection, with the potential for self-administration. According to Ionis, sefaxersen is the first RNA-targeted therapy being investigated specifically for IgAN. Roche licensed sefaxersen from Ionis for the treatment of complement-mediated diseases, with Ionis eligible for development and regulatory milestones as well as tiered royalties on potential future net sales.

Long-Term Kidney Function Remains Under Evaluation

Although the interim proteinuria results are positive, the IMAgINATION study remains ongoing. The trial will continue under blinded conditions to evaluate the longer-term effect of sefaxersen on kidney function through Week 105, with eGFR serving as an important measure of renal function. This longer-term analysis is intended to provide additional information about whether the reduction in proteinuria translates into preservation of kidney function over time. The safety and tolerability profile reported in the interim analysis was consistent with previously reported data, and no new safety signals were identified.

The companies plan to present the detailed interim findings at a future medical meeting and share the data with regulatory authorities as discussions continue regarding the development of sefaxersen. IgA nephropathy, also known as Berger’s disease, is a chronic and progressive autoimmune kidney disease that is commonly diagnosed in younger adults. Ionis reports that up to 50% of patients can progress to end-stage kidney disease within 20 years of diagnosis, creating a substantial need for therapies capable of addressing disease mechanisms and slowing long-term kidney deterioration. The positive Phase 3 interim results strengthen the clinical development program for sefaxersen and support continued investigation of RNA-targeted approaches in kidney disease. The upcoming detailed data presentation and the study’s longer-term kidney-function analysis will provide additional evidence on the potential role of sefaxersen in the treatment of IgA nephropathy.

Source: Ionis Pharmaceuticals, Roche press release