New Phase IIIB Data: Novartis Fabhalta® Improves Hemoglobin in PNH Patients Switching from Anti-C5 Therapy

Novartis has announced promising results from the APPULSE-PNH Phase IIIB study, which examines the effectiveness and safety of oral Fabhalta® (iptacopan) in adults with paroxysmal nocturnal hemoglobinuria (PNH) who switched from anti-C5 therapies. This study revealed that after 24 weeks, patients experienced an improvement in average hemoglobin (Hb) levels compared to their baseline.

Dr. Antonio Risitano, the trial’s lead investigator, emphasized the evolving treatment goals for PNH, noting the potential of Fabhalta to address the signs and symptoms of the disease. He highlighted that the results from APPULSE-PNH, along with findings from the APPLY-PNH and APPOINT-PNH trials, demonstrate Fabhalta's benefits for patients previously treated with anti-C5 therapies and those who are treatment-naive.

David Soergel, Global Head of Cardiovascular, Renal, and Metabolism Development at Novartis, reinforced the significance of this data, pointing out that Fabhalta is the first and only oral monotherapy available for PNH treatment, offering meaningful hemoglobin improvement regardless of prior treatments.

The APPULSE-PNH trial was a Phase IIIB, single-arm, open-label study involving 52 adults with PNH who had been on stable anti-C5 therapy regimens (eculizumab or ravulizumab) for at least six months before the trial. Participants had average Hb levels of 10g/dL or higher and hadn't required red blood cell transfusions during this period. The primary endpoint focused on the change in Hb levels after 24 weeks of Fabhalta monotherapy.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, chronic blood disorder caused by an acquired mutation in hematopoietic stem cells, leading to the production of red blood cells (RBCs) that are vulnerable to destruction by the complement system. This destruction occurs both within blood vessels (intravascular hemolysis) and in the spleen and liver (extravascular hemolysis), resulting in anemia, thrombosis, fatigue, and other symptoms. PNH affects approximately 10-20 people per million worldwide and is often diagnosed in individuals aged 30-40.

Current anti-C5 therapies, such as eculizumab and ravulizumab, are administered intravenously every 2-8 weeks, which can be time-consuming and inconvenient for patients. Despite these treatments, many PNH patients remain anemic and some continue to require blood transfusions.

Fabhalta (iptacopan) is an oral Factor B inhibitor targeting the alternative complement pathway. It received FDA approval in December 2023 for treating adults with PNH and EMA approval in May 2024 for treating adults with PNH and hemolytic anemia. In August 2024, the FDA granted accelerated approval for Fabhalta to reduce proteinuria in adults with primary immunoglobulin A nephropathy (IgAN) at risk of rapid disease progression. Ongoing studies are evaluating Fabhalta's safety and efficacy in other complement-mediated diseases, including C3 glomerulopathy, atypical hemolytic uremic syndrome, immune complex membranoproliferative glomerulonephritis, and lupus nephritis.

These results from the APPULSE-PNH trial underscore Fabhalta's potential to provide significant benefits for PNH patients, offering a more convenient oral treatment option with meaningful improvements in hemoglobin levels. This advancement marks a promising development in the management of PNH and highlights Novartis's commitment to addressing the needs of patients with rare and serious diseases.