Roche’s experimental kidney drug sefaxersen has delivered a statistically significant and clinically meaningful reduction in proteinuria in adults with IgA nephropathy (IgAN), raising hopes for a new treatment option for patients living with the progressive kidney disease.

 

Late-breaking Phase III data from the ongoing IMAgINATION study showed that sefaxersen reduced proteinuria by 43.1% compared with placebo at Week 37 among patients receiving optimised standard of care. The results were statistically significant (95% confidence interval), according to Roche.

 

Proteinuria, or excess protein in the urine, is a key indicator of kidney damage. Reducing protein levels is strongly associated with preserving long-term kidney function, making the findings significant for patients at risk of disease progression.

 

The study also found that a greater proportion of patients with blood in their urine at baseline achieved resolution of haematuria by Week 37 with sefaxersen than with placebo.

 

“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, Roche's Chief Medical Officer and Head of Global Product Development. 

 

“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.”

 

The treatment effect was consistent across all prespecified patient subgroups, reinforcing the proteinuria reductions reported in the primary endpoint analysis.

 

Roche said sefaxersen was well tolerated, with a safety profile consistent with the previously reported Phase II study. No new safety signals were identified.

 

The findings add to the evidence supporting sefaxersen, an investigational once-monthly subcutaneous injection designed to allow convenient self-administration by people with IgAN.

 

The IMAgINATION study will continue as a blinded trial to assess changes in kidney function over two years. The key measure will be estimated glomerular filtration rate (eGFR) at Week 105, which assesses how effectively the kidneys filter waste from the blood.

 

Roche said the data will be shared with health authorities, with the aim of bringing the treatment to patients as soon as possible.

 

A progressive disease with serious consequences

 

IgA nephropathy, also known as Berger’s disease, is a chronic, progressive autoimmune disease that can lead to kidney failure. Typically diagnosed before the age of 40, the condition affects at least 25 adults per million worldwide each year.

 

The disease is the most common form of primary glomerulonephritis, an inflammation of the kidneys’ tiny filtering units, and is a major cause of chronic kidney disease and kidney failure.

 

The long-term risks are substantial: up to 50% of patients with IgAN develop end-stage kidney disease within 20 years of diagnosis.

 

Against this backdrop, sefaxersen’s Phase III results offer encouraging evidence of its potential to address a key marker of kidney damage. However, the ongoing study’s two-year kidney function results will be important in determining whether the reduction in proteinuria translates into meaningful long-term benefits for patients.