Roche has announced positive Phase III results from the ongoing IMAgINATION study evaluating investigational sefaxersen in adults with primary immunoglobulin A nephropathy (IgAN). Presented as a late-breaking oral presentation at ASN Kidney Week 2026, the results showed a statistically significant 43.1% reduction in proteinuria at Week 37 compared with placebo, in patients receiving optimised standard of care.
The reduction was measured using the 24-hour urine protein-to-creatinine ratio (UPCR), a key indicator of kidney damage. The findings also showed that a greater proportion of patients with blood in their urine at baseline experienced resolution of haematuria with sefaxersen than with placebo.
Key Highlights
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43.1% reduction in proteinuria versus placebo at Week 37 (95% CI: 32.5–52.0; P<0.0001).
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Results were consistent across all prespecified patient subgroups.
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More patients with baseline haematuria achieved resolution by Week 37 with sefaxersen versus placebo.
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The treatment was generally well tolerated, with no new safety signals reported.
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The Phase III IMAgINATION study enrolled 459 participants and will continue to assess kidney function over 105 weeks.
Phase III IMAgINATION Study Results
The IMAgINATION trial is a multicentre, randomised, double-blind, placebo-controlled Phase III study evaluating the efficacy and safety of subcutaneous sefaxersen in adults with primary IgAN who are at high risk of disease progression.
A total of 459 participants were randomised in a 1:1 ratio to receive sefaxersen or placebo alongside optimised standard of care.
The primary endpoint was the change from baseline in urine protein-to-creatinine ratio at Week 37. Sefaxersen achieved a 43.1% reduction in proteinuria relative to placebo, with a 95% confidence interval of 32.5% to 52.0% and a P value below 0.0001.
The treatment effect was consistent across all prespecified subgroups, supporting the primary endpoint findings. Among participants with haematuria at baseline, a greater proportion receiving sefaxersen achieved haematuria resolution at Week 37 compared with placebo.
Sefaxersen Shows a Consistent Safety Profile
Sefaxersen was well tolerated, with a safety profile consistent with that observed in the earlier Phase II study. No new safety signals were identified in the Phase III results.
The study remains blinded and will continue to evaluate changes in kidney function over two years, with estimated glomerular filtration rate (eGFR) at Week 105 serving as a key measure of kidney function.
How Sefaxersen Works
Sefaxersen is an investigational antisense oligonucleotide (ASO) designed to reduce the production of complement factor B in the liver. Complement factor B plays a role in the alternative complement pathway, which contributes to inflammation and kidney damage in IgAN.
By reducing complement factor B levels, sefaxersen aims to address an underlying driver of the disease and reduce proteinuria. The treatment is designed as a once-monthly subcutaneous injection intended to support convenient self-administration.
Roche licensed sefaxersen from Ionis Pharmaceuticals for the treatment of complement-mediated diseases.
Understanding IgA Nephropathy
IgA nephropathy, also known as Berger’s disease, is a chronic and progressive kidney disease in which immune complexes containing immunoglobulin A accumulate in the kidneys. This can activate the complement system, trigger inflammation and damage the kidney’s filtering structures.
The disease is typically diagnosed before the age of 40 and affects at least 25 adults per million worldwide each year, according to Roche. It is the most common form of primary glomerulonephritis and can progress to end-stage kidney disease in up to 50% of patients within 20 years of diagnosis.
Proteinuria is an important indicator of kidney damage. Reducing protein levels in urine is a key treatment goal, alongside controlling blood pressure and slowing the decline in kidney function.
What Happens Next?
The IMAgINATION study will continue through Week 105 to assess the longer-term effects of sefaxersen on kidney function. Roche stated that the data will be shared with health authorities, with the aim of making the treatment available to patients as soon as possible.
Sefaxersen remains investigational, and the reported Phase III findings do not establish regulatory approval or confirm long-term preservation of kidney function. The ongoing study is expected to provide further evidence about its longer-term clinical effects.
