FDA Approves Fabhalta for C3G

“C3G is a debilitating disease often affecting young people, impacting many aspects of their physical and emotional health, and our previous treatment options came with significant challenges,” said Carla Nester, M.D., M.S.A., F.A.S.N., Professor of Pediatrics-Nephrology at the University of Iowa and Fabhalta APPEAR-C3G Study Co-Investigator. “This approval of Fabhalta is historic for the entire C3G community as now, for the first time, we have a therapy that is believed to treat the underlying cause of the disease, providing the potential for a new standard of care for patients.” 

Fabhalta is the only oral inhibitor of the alternative complement pathway to selectively target what is thought to be the underlying cause of the disease. Before the approval of Fabhalta, patients had to rely on supportive care, broad immunosuppression, and symptom management.  

 C3G is a progressive and ultra-rare kidney disease that, until now, has had no approved treatments^2-5. The average age of diagnosis is around 23 years old. Prognosis is poor, with approximately half of people living with C3G progressing to kidney failure within 10 years of diagnosis, requiring lifelong dialysis and/or kidney transplantation. People living with C3G may experience high levels of fatigue, mobility issues affecting everyday life activities, and mental health symptoms, including depression and anxiety.

 Data supporting approval ; The pivotal Phase III APPEAR-C3G study evaluated the efficacy and safety of twice-daily oral Fabhalta in adult patients with C3G. The study was comprised of a 6-month randomized, double-blind treatment period with Fabhalta compared to placebo in addition to supportive care, followed by an additional 6-month open-label treatment period where all participants received Fabhalta

 Treatment with Fabhalta resulted in clinically meaningful proteinuria reduction, which was seen as early as 14 days and sustained at 12 months. Similarly, in the open-label period, proteinuria reduction was seen in participants who switched to Fabhalta.   Fabhalta demonstrated a favorable safety profile, with no new safety signals. In patients with C3G, the most common adverse reactions (≥10%) with Fabhalta were nasopharyngitis and viral infections. Fabhalta may cause serious infections caused by encapsulated bacteria and is available only through a Risk Evaluation and Mitigation Strategy (REMS) that requires specific vaccinations. Last month, Fabhalta received a positive CHMP Opinion in C3G by the European Medicines Agency (EMA). Regulatory reviews for this indication are ongoing in China and Japan.

About APPEAR-C3G  ; APPEAR-C3G (NCT04817618) is a Phase III multicenter, randomized, double-blind, parallel group, placebo-controlled study to evaluate the efficacy and safety of twice-daily oral Fabhalta (200 mg) in patients with native kidney C3G.. The study comprises a 6-month double-blind period in which adult patients were randomized 1:1 to receive Fabhalta or placebo on top of supportive care, followed by a 6-month open-label period in which all patients receive Fabhalta (including those who were previously on placebo). The primary endpoint for the double-blind period was proteinuria reduction from baseline at 6 months for Fabhalta compared to placebo as measured by 24-hour urine protein-creatinine ratio (UPCR). In addition to the results from adult patients with C3G, enrollment is ongoing in a separate cohort of adolescent patients with C3G. 

About C3 glomerulopathy (C3G) ; Each year, approximately 1-2 people per million worldwide are newly diagnosed with C3G, a form of membranoproliferative glomerulonephritis (MPGN).