EMA has recommended granting a marketing authorisation in the European Union (EU) for Fabhalta (iptacopan), an oral treatment for adults with paroxysmal nocturnal haemoglobinuria (PNH) who have haemolytic anaemia.
PNH is a rare genetic disorder that causes the premature breakdown of red blood cells (haemolytic anaemia) by the immune system, and is potentially life-threatening. Disease symptoms include fatigue, body pain, blood clots, bleeding and shortness of breath. PNH generally worsens over time and patients often require red blood cell transfusions.
The standard treatment for PNH is anti-C5 monoclonal antibodies (eculizumab or ravulizumab), known as complement inhibitors, administered via subcutaneous or intravenous infusion. A minority of PNH patients treated with complement inhibitors suffer from residual haemolytic anaemia and require blood transfusions.
The active substance of Fabhalta is iptacopan, a proximal complement inhibitor. Complement inhibitors are a type of immunotherapy used in the treatment of many inflammatory conditions that could be caused by deficiencies of the complement system, a part of the body's immune system. Iptacopan targets Factor B to selectively inhibit the alternative complement pathway and prevent the destruction of red blood cells within blood vessels (intravascular haemolysis) and in the liver and spleen (extravascular haemolysis).
EMA’s recommendation is based on the results of two phase III trials. The pivotal study was a randomised, open-label, active-comparator trial which enrolled 97 PNH patients with residual anaemia despite receiving anti-C5 regimen for at least 6 months prior to randomisation. Patients received iptacopan monotherapy (n=62) or continued their anti-C5 regimen (n=35) for 24 weeks.
The treatment with Fabhalta was significantly superior to the anti-C5 regimen, with 51 of 60 evaluable patients achieving haemoglobin improvement (≥2 g/dl) and 42 achieving sustained haemoglobin levels (≥12 g/dl) in the absence of transfusion, compared to no patients treated with the anti-C5 regimen. In addition, 59 of 62 patients treated with Fabhalta group did not require blood transfusions between day 14 and day 168, compared to 14 of 35 patients in the anti-C5 group.
The other trial was a single-arm study in 40 PNH patients treated with Fabhalta who had not been previously treated with a complement inhibitor. At week 24, 31 of the 33 evaluable patients achieved haemoglobin improvement (≥2 g/dl) and 19 achieved sustained haemoglobin levels (≥12 g/dl) in the absence of transfusion. No patients required transfusions.
The most frequent side effects in patients treated with Fabhalta were upper respiratory tract infection, headache and diarrhea.
Fabhalta was supported through EMA's PRIority MEdicines (PRIME) scheme, which provides early and enhanced scientific and regulatory support to medicines that have a particular potential to address patients' unmet medical needs.
The opinion adopted by the CHMP is an intermediary step on Fabhalta’s path to patient access. The opinion will now be sent to the European Commission for the adoption of a decision on an EU-wide marketing authorisation. Once a marketing authorisation has been granted, decisions about price and reimbursement will take place at the level of each Member State, taking into account the potential role or use of this medicine in the context of the national health system of that country.
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