Novartis Korea cleared to expand Fabhalta indication to adult C3G patients

Novartis Korea said its factor B inhibitor Fabhalta (ingredient: iptacopan) has received expanded approval from the Ministry of Food and Drug Safety on Tuesday as a treatment option for adults aged 18 and older with complement 3 glomerulopathy (C3G).

C3G is a rare chronic glomerulonephritis caused by dysregulation and overactivation of the alternative complement pathway.

Excessive activation of complement component C3 leads to the accumulation of C3 activation products in the glomeruli, driving inflammation and progressive renal tissue damage. About 50 percent of patients diagnosed with C3G progress to end-stage renal disease within 10 years.

Among patients who undergo kidney transplantation, up to 66.7 percent experience recurrence of C3G, and as many as 50 percent lose their graft within a median of 6.4 years if the disease recurs. Patients commonly present with proteinuria, hematuria, edema, hypertension, and fatigue.

Since C3G was first defined as an independent disease in 2013, therapeutic strategies have remained limited to supportive management such as controlling proteinuria and blood pressure, while moderate to severe patients have typically received immunosuppressive therapy. No established optimal treatment existed before targeted complement inhibitors emerged.

Fabhalta is the first-in-class oral complement inhibitor that directly addresses the underlying mechanism of C3G. The drug selectively binds to factor B, a key protein in the alternative complement pathway, thereby blocking pathway activation and reducing the deposition of C3 in the glomeruli.

The new indication is supported by results from the APPEAR-C3G trial, a multinational, randomized, double-blind, placebo-controlled phase 3 study involving 74 adults with biopsy-confirmed C3G. Participants received oral Fabhalta 200 milligrams twice daily. The study evaluated reductions in twenty-four-hour urine protein-to-creatinine ratio and stabilization of estimated glomerular filtration rate.

At month six, the Fabhalta group recorded a 30.2 percent reduction in proteinuria from baseline compared with a 7.6 percent increase in the placebo group, amounting to a statistically significant 35.1 percent difference between the groups.

The composite renal endpoint, defined as at least a 50 percent reduction in proteinuria with no more than a 15 percent decline in eGFR, was achieved in 30 percent of Fabhalta-treated patients and six percent of those receiving placebo at month six, rising to 45 percent at month twelve in the treatment arm.

The effects were consistent even in patients receiving concurrent immunosuppressants or renin–angiotensin system inhibitors, and clinical responses strengthened with continued therapy.

Fabhalta showed a favorable safety profile in the phase 3 study, with no treatment discontinuations or deaths related to adverse events. Most adverse reactions were mild to moderate in severity.

“C3G is a rare kidney disease with extremely limited treatment options and poor prognosis, and patients have long been confined to supportive therapy only,” said Lee Ha-jung, professor of nephrology at Seoul National University Hospital. “The expanded approval of Fabhalta is highly meaningful, as it offers new hope to patients who previously had no effective disease-modifying therapy.”

With the availability of a therapy that targets the root cause of C3G, we expect more patients to receive accurate diagnosis and timely treatment, Lee aid.

Fabhalta was first approved in August 2024 in Korea as a treatment for adults with paroxysmal nocturnal hemoglobinuria. Since July 1 of this year, reimbursement has been available for adults with PNH who cannot receive C5 inhibitors such as eculizumab or ravulizumab, or who meet reimbursement criteria for C5 inhibitors but require switching therapy after at least six months of use due to insufficient hemoglobin response below 10 g/dL or treatment-related adverse effects.