Novartis, on a roll with newly approved Fabhalta, touts its promise in another rare blood disease

Less than a week after gaining its first of what it hopes are several FDA approvals for its oral Factor B inhibitor Fabhalta (iptacopan) for blood disorders, Novartis has presented promising data from a trial in another indication.

Without revealing numbers, Novartis said that the APPEAR-C3G phase 3 study of patients with C3 glomerulopathy (C3G) demonstrated that iptacopan provided clinically meaningful and statistically significant reduction in proteinuria (protein in the urine) compared to placebo after six months of use.

C3G is one of the rarer complement-mediated kidney diseases that Novartis hopes to address with iptacopan. Within 10 years of diagnosis, approximately 50% of those with C3G have kidney failure. There are no treatments that address the underlying cause of C3G.

Last week, the FDA signed off on Fabhalta, making it the first oral monotherapy to treat paroxysmal nocturnal hemoglobinuria (PNH).

In APPEAR-C3G, patients received background therapy, with those in the experimental arm taking twice-daily 200 mg doses of iptacopan. The trial met its primary endpoint with the safety profile measuring up to previous studies of iptacopan, Novartis said.

The study will continue for six more months, with all patients receiving ipactopan, including those who were on placebo. During this open-label period, proteinuria reduction at 12 months will be the primary endpoint. A comparison of proteinuria reduction for 12 months versus six months also will be measured.

Secondary endpoints include the change in estimated glomerular filtration rate (eGFR), the proportion of participants meeting the composite renal endpoint criteria, change in glomerular inflammation and change in patient-reported fatigue.

Because C3G often strikes younger people, Novartis also is enrolling adolescent patients in a separate study.

Novartis will review the results with regulators around the world to generate potential submissions in 2024, it said. At an upcoming medical meeting, the company will provide detailed stats for APPEAR-C3G.

The disease is an overactivation of the alternate complement pathway, which is part of the immune system, and causes protein buildup in the kidney. It is diagnosed in 1-2 people per million around the world, presenting mostly in children and young adults. Treatments aim to control blood pressure, cholesterol and proteinuria. Patients who have heart failure require dialysis and/or kidney transplant, with 55% of transplant patients having recurrence of the disorder.

The trial results are more positive momentum for iptacopan, which has been dubbed “a pipeline in a pill” by analysts at ODDO BHF. Analysts at Jefferies have pegged iptacopan’s peak sales potential at $3.6 billion.

The biggest opportunity for Novartis with the treatment is in primary immunoglobulin A neuropathy (IgAN), also known as Berger’s disease. Data released in October from the phase 3 study showed that iptacopan hit its pre-specified interim endpoint with significant proteinuria reductions, putting it on course for a potential fast-track approval in 2024.

Other indications Novartis is investigating for iptacopan include atypical hemolytic uremic syndrome (aHUS) and immune complex membranoproliferative glomerulonephritis (IC-MPGN).