Novartis oral Fabhalta receives positive EMA Committee opinion for adults with C3 glomerulopathy
Basel: Novartis has announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has adopted a positive opinion and recommended granting a marketing authorization for Fabhalta (iptacopan) – a first-in-class oral Factor B inhibitor of the alternative complement pathway – for the treatment of adults with C3 glomerulopathy (C3G).
There are currently no approved treatments for patients living with C3G, a progressive ultra-rare kidney disease, which often strikes when people are young. The prognosis for people living with C3G is poor, with around half of patients progressing to kidney failure within 10 years of being diagnosed, at which point they require lifelong dialysis and/or kidney transplantation.
“C3G is a debilitating condition, often affecting young people and severely impacting their physical and mental health,” said Marianne Silkjær Nielsen, Founder of CompCure, a Danish non-profit association committed to improving outcomes for individuals with C3G and immune complex membranoproliferative glomerulonephritis (IC-MPGN). “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.”
The CHMP’s opinion is based on robust data from APPEAR-C3G, the first randomized, placebo-controlled Phase III study in C3G. The study showed patients treated with Fabhalta, in addition to supportive care, achieved a statistically significant and clinically meaningful 35.1% (p=0.0014) reduction in proteinuria (as measured by 24-hour urine protein to creatinine ratio [UPCR]) at 6 months when compared to placebo. In many kidney diseases, proteinuria reduction is an increasingly recognized surrogate marker correlating with delaying progression to kidney failure. Additional data on the secondary endpoint of estimated glomerular filtration rate (eGFR), a measure of kidney function, showed a numerical improvement of +2.2 mL/min/1.73 m2 (p=0.3241) over 6 months with Fabhalta compared to placebo. The eGFR remained stable during the 12 months duration of the study in the iptacopan treatment arm (+0.4 ml/min/1.73 m2 from baseline). In a long-term extension study, the initial UPCR reduction was maintained and stabilization of eGFR was observed over more than 3 years after initiation of the treatment with Fabhalta.
“C3G has no approved treatments, and patients face challenges with current options,” said Professor David Kavanagh, Professor of Complement Therapeutics & Honorary Consultant Nephrologist at the National Renal Complement Therapeutics Centre at Newcastle University and APPEAR-C3G Steering Committee Member. “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.”
Across the Fabhalta C3G program, which includes over 100 C3G patients, Fabhalta was well tolerated. The safety profile in C3G patients was consistent with the one established in the PNH indication, with no new safety signals reported in the C3G population6-8.
“If approved, Fabhalta will be the first C3G treatment available for patients living with this severe progressive disease.” said David Soergel, M.D., 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.”
Following the CHMP’s recommendation to approve Fabhalta for the treatment of adults with C3G, the European Commission (EC) will make a final decision within two months.
