Novartis has announced positive topline results from the Phase IIIB APPULSE-PNH study, evaluating Fabhalta (iptacopan) in adult patients with paroxysmal nocturnal hemoglobinuria (PNH) who switched from anti-C5 therapies. The study demonstrated that Fabhalta, a twice-daily oral monotherapy, improved average hemoglobin levels versus baseline after 24 weeks of treatment.
The APPULSE-PNH trial enrolled 52 participants who had been stabilized on anti-C5 therapies (eculizumab or ravulizumab) for at least 6 months, with baseline Hb levels of at least 10 g/dL and no recent transfusions. The primary endpoint was the change from baseline Hb levels after 24 weeks of treatment with Fabhalta.
Improved Hemoglobin Levels with Fabhalta
According to Antonio Risitano, M.D., Ph.D., Chair of the International PNH Interest Group and lead investigator of the APPULSE-PNH trial, "These new results add to the body of evidence reinforcing that Fabhalta can benefit both patients previously treated with anti-C5 therapies studied in the APPULSE-PNH and APPLY-PNH trials and complement-inhibitor naïve patients studied in the APPOINT-PNH trial. Treatment goals for patients with PNH have greatly evolved, and we can now aim to resolve signs and symptoms of disease in most patients."
The safety profile of Fabhalta monotherapy was consistent with previously reported data. David Soergel, M.D., Global Head, Cardiovascular, Renal and Metabolism Development Unit, Novartis, stated, "Across multiple clinical trials, Fabhalta has consistently shown clinically meaningful benefits for patients with PNH, and the APPULSE-PNH trial is a compelling addition to this body of evidence. These data reinforce our confidence in Fabhalta, the first and only oral monotherapy currently available for the treatment of adults with PNH, to provide meaningful hemoglobin improvement, regardless of previous treatment experience."
Fabhalta's Regulatory Status and Further Development
Fabhalta received FDA approval in December 2023 for the treatment of adults with PNH and EMA approval in May 2024. It was also granted accelerated approval by the FDA for reducing proteinuria in adults with primary immunoglobulin A nephropathy (IgAN). Fabhalta is being studied in a range of rare kidney diseases, including C3 glomerulopathy (C3G), atypical hemolytic uremic syndrome (aHUS), immune complex membranoproliferative glomerulonephritis (IC-MPGN), and lupus nephritis (LN).
Expanding Access to Fabhalta
The Max Foundation has expanded its collaboration with Novartis to provide access to iptacopan for treating PNH in low-resource countries. This initiative will offer treatment at no cost to patients in 53 countries across Sub-Saharan Africa, Latin America, the Caribbean, and parts of Asia.
Impact on Quality of Life
Data from the APPLY-PNH and APPOINT-PNH trials, presented at the American Society of Hematology (ASH) Annual Meeting 2024, demonstrated notable improvements in patient-reported health-related quality of life (HRQOL) with iptacopan. Patients reported improvements in all functional domains of the EORTC QLQ-C30, global health status, and reductions in key PNH symptoms such as fatigue and dyspnea.
