Fabhalta raises hemoglobin, ends transfusion need in PNH patients
Study tested therapy in adults who switched from Soliris orĀ Ultomiris
Six months of Fabhalta (iptacopan) raised hemoglobin levels, eliminated the need for blood transfusions, and eased fatigue in most adults with paroxysmal nocturnal hemoglobinuriaĀ (PNH) who switched from standard anti-C5 therapies.
Thatās according to data from the open-label Phase 3b APPULSE-PNH (NCT05630001) that evaluated the therapy’s efficacy and safety in patients on a stable regimen of either SolirisĀ (eculizumab) orĀ Ultomiris (ravulizumab) for at least six months without moderate or severe anemia.
The results “APPULSE-PNH: Oral iptacopan monotherapy demonstrates clinically meaningful hemoglobin (Hb) increases in patients (pts) with paroxysmal nocturnal hemoglobinuria (PNH) and Hb ā„10 g/dL on anti-C5 therapy,” were presented at the European Hematology Association (EHA) Congress 2025 this month in Milan and online. The results expanded the clinical evidence showing the efficacy of Fabhalta across different PNH populations, the researchers said.
āNew data from APPULSE-PNH, combined with findings from the Phase III rollover extension of the APPLY-PNH and APPOINT-PNH studies, reinforce the efficacy and safety profile of Fabhalta in delivering real benefits to patients,ā Shreeram Aradhye, MD, Novartisā president, development and chief medical officer, said in a company press release. āFabhalta is the first and only oral monotherapy currently available for the treatment of adults with PNH, regardless of previous treatment experience.”
PNH is caused by the abnormal activation of the complement cascade, a group of immune proteins, which leads to the destruction of red blood cells, or hemolysis. This results in decreased hemoglobin, the protein responsible for carrying oxygen in red blood cells, leading to anemia and other symptoms.
Soliris and Ultomiris target the complement protein C5 and block complement activation, preventing red blood cell destruction. While they can prevent red blood cell destruction inside blood vessels, called intravascular hemolysis, hemolysis may still occur outside blood vessels (extravascular hemolysis).
What is Fabhalta?
Fabhalta is an oral therapy approved in the U.S. for adults with PNH. It suppresses factor B, a key protein in the alternative complement pathway that acts upstream of C5,Ā thus stopping both intra- and extravascular hemolysis.
Its approval was based on data from two Phase 3 clinical trials, APPOINT-PNH (NCT04820530)Ā andĀ APPLY-PNH (NCT04558918), which enrolled patients never treated with complement inhibitors and patients who had anemia despite treatment with C5-inhibitors, respectively.
Final data from both showed that a year of treatment significantly increased hemoglobin, with good control of intravascular and extravascular hemolysis, eliminated the need for blood transfusions, and eased fatigue in most participants.
In APPULSE-PNH, 52 adults with PNH were treated with C5 inhibitors for six months, during which time their hemoglobin levels were at least 10 grams per deciliter of blood (g/dL, meaning they didn’t have moderate or severe anemia) and they didn’t require blood transfusions. All switched to 200 mg twice daily of Fabhalta for about six months.
Most (88.5%) transitioned from Ultomiris. The treatment resulted in a significant increase in hemoglobin of about 2 g/dL, with most achieving a hemoglobin level of at least 12 g/dL after six months. No patients required blood transfusions, experienced a breakthrough hemolysis event, or had other major vascular events.
Beyond blood counts, patients also reported a reduction in fatigue. Their FACIT-Fatigue scores improved by 4.88 points after about three months and 4.29 points after about five and a half months. The participants were largely satisfied with Fabhalta’s effectiveness and convenience.
āThe positive results from APPULSE-PNH reinforce that Fabhalta can provide clinically meaningful improvements in hemoglobin among patients with higher baseline hemoglobin levels than those enrolled in previous trials, while offering an oral monotherapy for patients,ā said Austin Kulasekararaj, MD, consultant hematologist at Kings College Hospital and Kings College London.
The most frequent adverse events were headache (17.3%), diarrhea, nausea, and common cold (11.5% each). Two participants had serious adverse events that were considered not related to the treatment and one patient discontinued Fabhalta due to nonserious heart palpitations considered related to treatment.
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