Novartis has shared favorable initial findings from the APPULSE-PNH study, a Phase IIIB trial that assesses the effectiveness and safety of the twice-daily oral drug Fabhalta (iptacopan) for adults with paroxysmal nocturnal hemoglobinuria (PNH) who previously underwent anti-C5 therapies. Post 24 weeks of treatment with Fabhalta, there was a noticeable improvement in average haemoglobin levels compared to the baseline.
“These new findings further substantiate that Fabhalta is advantageous for patients previously on anti-C5 therapies, as seen in the APPULSE-PNH and APPLY-PNH studies, as well as for complement-inhibitor naïve patients explored in the APPOINT-PNH trial,” stated Dr. Antonio Risitano, Chair of the International PNH Interest Group and the lead investigator for the APPULSE-PNH trial. “The goals in managing PNH have substantially advanced, and now there is potential to alleviate most of the disease’s manifestations and symptoms in patients. This progression is encouraging, and our efforts to support these patients persist.”
The safety profile for Fabhalta has remained consistent with previous data throughout the study.
“In multiple studies, Fabhalta has demonstrated significant clinical benefits for PNH patients,” remarked Dr. David Soergel, global leader for cardiovascular, renal, and metabolic development at Novartis. “The APPULSE-PNH findings further solidify our trust in Fabhalta as a solitary oral treatment for adults with PNH, showcasing notable improvements in haemoglobin, irrespective of previous treatments.”
The study’s insights will be presented at an upcoming medical conference slated for 2025. Notably, Fabhalta recently received FDA accelerated approval for its role in mitigating proteinuria in adults with primary immunoglobulin A nephropathy, with further developments underway for several complement-mediated conditions.
**Trial Overview: APPULSE-PNH (NCT05630001)**
This Phase IIIB multicenter, open-label study explores the efficacy and safety of a twice-daily dosage of oral Fabhalta (iptacopan) in adults transitioning from anti-C5 therapies (eculizumab or ravulizumab). Enrolling 52 individuals, the trial spanned 24 weeks.
**Participant Requirements:**
Achieving a stable regimen with anti-C5 treatment for at least half a year before the screening, participants had average haemoglobin levels =10g/dL and experienced no red blood cell transfusions during that period. The main objective was to observe the haemoglobin level change post 24-week Fabhalta treatment.
**About Paroxysmal Nocturnal Hemoglobinuria (PNH):**
PNH is a rare, serious disorder where an acquired mutation in stem cells causes susceptibility to premature red blood cell destruction, leading to haemolysis, anemia, thrombosis, fatigue, and other severe symptoms.
Approximately 10-20 individuals per million have PNH worldwide, often diagnosed between ages 30-40.
**Current Treatment Challenges:**
Anti-C5 therapies, administered intravenously every 2-8 weeks, have significant time demands, with many patients remaining anemic and dependent on blood transfusions.
🌿 **About Fabhalta (iptacopan):**
Fabhalta functions as an oral Factor B inhibitor affecting the alternative complement pathway. Approved by the FDA in December 2023 for adults with PNH and the EMA in May 2024 for treating PNH with haemolytic anemia, it continues to be developed for a range of rare kidney diseases and complement-mediated conditions.