Roche has announced positive interim results from its ongoing Phase III IMAgINATION study evaluating sefaxersen, an investigational treatment for adults living with primary IgA nephropathy (IgAN). According to the company, the study achieved its primary endpoint, with sefaxersen producing a statistically significant and clinically meaningful reduction in proteinuria compared with placebo at 37 weeks.
The results are significant because proteinuria, or excess protein in the urine, is an important marker of kidney damage. A reduction in the urine protein-to-creatinine ratio (UPCR) is associated with preservation of kidney function over the longer term. In the IMAgINATION study, the change in UPCR at week 37 was the primary endpoint used to assess the treatment.
Sefaxersen is being developed as a once-monthly subcutaneous injection that is intended to allow self-administration. The treatment works by reducing production of complement factor B in the liver, targeting the alternative complement pathway involved in the disease process of IgA nephropathy.
IgA nephropathy, also known as Berger’s disease, is a chronic autoimmune kidney disorder in which immune complexes accumulate in the kidneys and trigger inflammation. Over time, this can lead to progressive kidney damage and, in some patients, kidney failure. Roche cites evidence indicating that up to 50% of people with IgAN may progress to end-stage kidney disease within 20 years of diagnosis.
The Phase III IMAgINATION trial enrolled 459 participants with primary IgA nephropathy who were considered at high risk of disease progression. Participants were randomly assigned to receive either sefaxersen or placebo, with the study designed as a multicentre, randomised, double-blind and placebo-controlled trial. Treatment and follow-up are planned over 105 weeks.
While the interim findings showed a positive effect on proteinuria, the study is not yet complete. Roche said the trial will continue in a blinded manner to evaluate changes in kidney function, including estimated glomerular filtration rate (eGFR), at week 105. This longer-term assessment will provide additional information about whether the reduction in proteinuria translates into preservation of kidney function.
The company also reported that the safety and tolerability profile observed with sefaxersen was consistent with previously reported findings, with no new safety signals identified in the interim analysis.
Roche plans to present the interim findings at an upcoming medical congress and share the data with health authorities. Since sefaxersen remains an investigational medicine, the latest results do not mean that the treatment is approved for routine clinical use. Regulatory authorities will need to review the complete clinical evidence before any potential approval.
The development of sefaxersen reflects growing interest in treatments that target specific biological mechanisms involved in IgA nephropathy rather than focusing only on controlling the consequences of kidney damage. Updated KDIGO guidance has also highlighted the importance of addressing both the immune mechanisms underlying IgAN and the downstream effects of kidney injury.
For patients with IgA nephropathy, the key question will ultimately be whether newer targeted therapies can provide sustained protection against declining kidney function and reduce the number of people progressing to dialysis or kidney transplantation. The ongoing IMAgINATION study is expected to provide further evidence on this aspect as longer-term results become available.
