The European Medicines Agency (EMA) has granted Novartis Europharm marketing authorization for Fabhalta (Iptacopan) for the treatment of adults with paroxysmal nocturnal hemoglobinuria (PNH) and hemolytic anemia.
The decision was celebrated as the first step towards enabling patient access in European Union countries following a meeting of the Committee for Medicinal Products for Human Use (CHMP) on March 21.
PNH is a rare, debilitating, and potentially life-threatening genetic disease that causes hemolytic anemia. Symptoms of the disease include fatigue, body pain, blood clots, bleeding, and shortness of breath. The standard treatment involves monoclonal anti-C5 antibodies (Eculizumab or Ravulizumab) administered via subcutaneous or intravenous infusion. However, a minority of PNH patients treated with these complement inhibitors experience residual hemolytic anemia and require red blood cell transfusions.
The active ingredient in Fabhalta is Iptacopan, a proximal complement inhibitor. Iptacopan targets factor B to selectively inhibit the alternative complement pathway and control both C3-mediated extravascular hemolysis and terminal complement-mediated intravascular hemolysis.
Superior Results in Phase 3 Studies
The decision to grant marketing authorization was based on an evaluation of two Phase 3 studies. The main study was a randomized, open-label, active comparator study involving 97 PNH patients who had residual anemia despite treatment with monoclonal anti-C5 antibodies in the last 6 months. Of the participants, 62 received Iptacopan monotherapy and 35 continued their anti-C5 therapy for 24 weeks.
It was found that treatment with Fabhalta was significantly superior to anti-C5 therapy: 51 out of 60 patients assessed achieved a hemoglobin improvement (≥ 2 g/dl) and 42 achieved sustained hemoglobin levels (≥ 12 g/dl) without transfusion, compared to no patients continuing treatment with monoclonal anti-C5 antibodies. Additionally, 59 out of 62 patients treated with Fabhalta did not require blood transfusions between day 14 and day 168, compared to 14 out of 35 patients in the anti-C5 group.
The second study was a single-arm study involving 40 PNH patients who had not previously been treated with a complement inhibitor. Following treatment with Fabhalta, 31 out of 33 evaluable patients reached a hemoglobin improvement (≥ 2 g/dl) in week 24, while 19 achieved sustained hemoglobin levels (≥ 12 g/dl) without transfusion.
The most common side effects of Fabhalta are upper respiratory tract infections, headaches, and diarrhea.
The CHMP emphasized that Fabhalta should be prescribed by physicians with experience in treating patients with hematologic disorders.
Fabhalta was supported by the European Medicines Agency’s Priority Medicines (PRIME) program, which provides regulatory support for promising medications that have the potential to address unmet medical needs. The CHMP’s recommendation has been forwarded to the European Commission for a final decision.
In a statement on March 22, Novartis noted that Fabhalta, if approved, would be the first oral monotherapy available to PNH patients in Europe.