Novartis Treatment for C3G Gets Positive Opinion from EMA

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The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has given a positive opinion and recommendation for marketing authorization to Fabhalta (iptacopan), a Novartis treatment for adults with C3 glomerulopathy (C3G) (1). Highlights from CHMP’s February 24–27 meeting described C3G as “ultra-rare” and clarified that Fabhalta has already been granted orphan drug designation (1,2).

Novartis announced CHMP’s decision in a press release on February 28, which was the 2025 edition of Rare Disease Day. Since 2008, this occasion has been recognized on the final day of February, including February 29 in leap years—the rarest date on the calendar.

C3G is a progressive kidney disease often affecting young adults, and the prognosis is poor, according to Novartis; approximately half of patients progress to kidney failure within 10 years of diagnosis and thereafter require lifelong dialysis and/or a kidney transplant (1).

CHMP’s opinion was based on data from a randomized, placebo-controlled Phase III study (APPEAR-C3G) that Novartis said achieved a statistically significant and clinically meaningful 35.1% reduction in proteinuria using iptacopan versus placebo after six months (1).

“C3G has no approved treatments, and patients face challenges with current options,” David Kavanagh, professor of complement therapeutics and honorary consultant nephrologist at the National Renal Complement Therapeutics Centre at Newcastle University, UK, and APPEAR-C3G Steering Committee Member, said in the Novartis press release (1). “With its strong body of evidence, oral Fabhalta targets the underlying cause of C3G in both native and recurrent patients and can bring hope to patients who currently have a poor prognosis.”

As Kavanagh mentioned, Fabhalta is an oral, Factor B inhibitor of the alternative complement pathway that previously received FDA and European Commission approval in December 2023 and May 2024, respectively, for treatment of adults with paroxysmal nocturnal hemoglobinuria (1). FDA also granted iptacopan accelerated approval in August 2024 for reduction of proteinuria in adults with primary IgA nephropathy at risk of rapid disease progression. It is currently being studied, according to Novartis, for use in treating other rare kidney diseases such as atypical hemolytic uremic syndrome, immune complex membranoproliferative glomerulonephritis (IC-MPGN), and lupus nephritis.

In the Fabhalta C3G program, comprised of more than 100 patients, the drug was well-tolerated, according to Novartis (1).

“C3G is a debilitating condition, often affecting young people and severely impacting their physical and mental health,” Marianne Silkjær Nielsen, founder of CompCure, a Danish nonprofit committed to improving outcomes for individuals with C3G and IC-MPGN, said in the Novartis press release. “Screening to secure timely diagnosis and access to targeted treatments are critical for patients, their families and society. This milestone is highly welcomed by the patient community, marking progress toward better patient care for people living with C3G.”

“If approved, Fabhalta will be the first C3G treatment available for patients living with this severe progressive disease,” said David Soergel, MD, global head, Cardiovascular, Renal and Metabolism Development Unit, Novartis. “Building on our longstanding expertise in nephrology and recent advancements in kidney diseases, this positive CHMP opinion marks an important step forward for our exciting multi-asset kidney pipeline, underscoring our commitment to making meaningful progress for patients with unmet needs.”

References

1. Novartis. Novartis Oral Fabhalta (iptacopan) Receives Positive CHMP Opinion for the Treatment of Adults Living with C3 Glomerulopathy (C3G). Press Release. Feb. 28, 2025.
2. EMA. Meeting Highlights from the Committee for Medicinal Products for Human Use (CHMP) 24–27 February 2025. Press Release. Feb. 28, 2025.