Biogen publishes Phase 3 EMPAVELI paediatric data in CJASN

Biogen has published results from a prespecified adolescent subgroup analysis of its Phase 3 VALIANT study in the Clinical Journal of the American Society of Nephrology, showing that pegcetacoplan (EMPAVELI) produced substantial reductions in proteinuria and stabilised kidney function in patients aged 12 to 17 with C3 glomerulopathy (C3G) or primary immune complex membranoproliferative glomerulonephritis (IC-MPGN).

The cohort of 55 adolescents treated with EMPAVELI achieved a 75% relative reduction in proteinuria at week 26 versus placebo (95% CI: 59% to 84%; nominal p<0.001), with responses observed as early as week four. Seventy-one per cent of the treated group achieved at least a 50% reduction in proteinuria, compared with 4% on placebo. A combined endpoint of stable kidney function alongside at least a 50% proteinuria reduction was reached by 57% of EMPAVELI-treated adolescents versus 4% on placebo, an outcome particularly relevant given that progressive kidney disease in this population can lead to transplant within a decade.

Clinical significance

Adolescents made up nearly half of the full VALIANT population of 124 patients, giving the subgroup analysis one of the largest randomised datasets in this age group for both conditions. Bradley Dixon, Section Chief of Paediatric Nephrology at the University of Colorado School of Medicine and Children's Hospital Colorado, noted that the adolescent findings were "consistent with what we observed in the broader population" and described them as "especially encouraging for young patients who may otherwise face a lifetime of progressive kidney disease leading to a potential kidney transplant."

The publication follows a recent FDA label update expanding EMPAVELI's indication to include reducing the loss of kidney function, in addition to proteinuria reduction, in patients aged 12 and older. Biogen says the drug is now the first and only therapy approved in the United States for both endpoints in adults and adolescents with C3G or primary IC-MPGN. The safety profile in the adolescent cohort was consistent with the overall study population; the most common adverse reactions included infusion-site reactions, pyrexia, nasopharyngitis and nausea. EMPAVELI carries a boxed warning for serious encapsulated bacterial infections and is available only through a Risk Evaluation and Mitigation Strategy programme.

Market context

C3G and primary IC-MPGN are rare complement-mediated nephropathies. Approximately half of C3G patients are diagnosed before the age of 18, and roughly 20% of affected children progress to kidney failure within 10 to 15 years of diagnosis. The complement inhibition space has attracted considerable attention in recent years, with several large-cap biotechs and specialist rare-disease developers pursuing C3, C5 and factor B as therapeutic targets. Biogen's C3 proximal approach with pegcetacoplan differentiates from terminal complement inhibitors such as eculizumab and ravulizumab, which target C5 and are not approved for this indication, though head-to-head data versus those agents are not available.

For Biogen, the VALIANT dataset and label expansion represent a meaningful addition to its rare-disease portfolio at a time when the company is managing near-term revenue pressure in its more established neuroscience lines. The paediatric label broadens the addressable population at launch and may support reimbursement negotiations in markets where paediatric data are required for formulary access. Clinicians and payers will be watching for longer-term eGFR trajectory data as the 52-week open-label extension results are disseminated.