PNH treatment Fabhalta boosts hemoglobin in patients who switch
Top-line trial data show benefits for those formerly on standard therapy
Six months of twice-daily treatment with oral Fabhalta (iptacopan) improved hemoglobin levels in adults with paroxysmal nocturnal hemoglobinuria (PNH) who switched from standard anti-C5 therapies, according to top-line results from a Phase 3 clinical trial.
Dubbed APPULSE-PNH (NCT05630001), the now-complete study tested Novartis’ therapy in 52 adults with PNH. Participants had been on a stable regimen of either of the anti-C5 therapies Soliris (eculizumab) or Ultomiris (ravulizumab) for at least six months without signs of anemia.
“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,” David Soergel, MD, global head of the cardiovascular, renal and metabolism development unit at Novartis, said in a company press release.
In PNH, the abnormal activation of a group of immune proteins known as the complement cascade leads to the destruction of red blood cells (hemolysis). As a result, the levels of hemoglobin, the protein that carries oxygen in red blood cells, drop, leading to anemia and other symptoms.
Soliris and Ultomiris are approved PNH therapies that help prevent blood cell destruction by targeting a protein called C5 and blocking complement activation. While the therapies are effective at preventing red blood cell destruction taking place inside blood vessels, 10% to 20% of patients still require blood transfusions due to red blood cell destruction occurring outside blood vessels.
Stopping hemolysis
Fabhalta is an oral therapy approved in the U.S. for adults with PNH. It’s designed to stop hemolysis occurring both inside and outside blood vessels by suppressing factor B, a protein that acts upstream, or before, C5 in the cascade of complement activation.
Data from two Phase 3 clinical trials, APPOINT-PNH (NCT04820530) and APPLY-PNH (NCT04558918) supported Fabhalta’s approval.
Of the 40 PNH patients enrolled in APPOINT-PNH who were naïve, or had never been on complement-inhibitor treatment, most responded substantially to Fabhalta. Among the 97 adults in APPLY-PNH who experienced ongoing anemia despite treatment with Soliris or Ultomiris, Fabhalta also improved responses.
APPULSE-PNH enrolled 52 adults with PNH who had been on Soliris or Ultomiris for at least six months without signs of anemia. During this period, participants maintained an average hemoglobin level of at least 10 grams per deciliter and did not require red blood cell transfusions.
All patients switched to 200 mg of Fabhalta twice daily for 24 weeks, or about six months. Based on a physician’s assessment, those who benefited from the new treatment during the 24-week phase could join a rollover extension study.
The trial’s main goal was to evaluate whether the therapy was not inferior to standard anti-C5 treatment at preventing a reduction in hemoglobin levels. Secondary goals included assessing changes in hemoglobin levels demonstrating Fabhalta’s superiority, the proportion of patients with a blood-based response, changes in hemolysis markers, and treatment satisfaction.
According to Novartis, Fabhalta improved average hemoglobin levels over the course of 24 weeks of treatment.
“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,” said Antonio Risitano, MD, PhD, APPULSE-PNH’s lead investigator and head of the hematology and hematopoietic transplant unit at the Reference Center for Aplastic Anemia and Paroxysmal Nocturnal Hemoglobinuria at the AORN San Giuseppe Moscati in Italy.
In APPULSE-PNH, Fabhalta’s safety profile was consistent with previously reported data. The company said these data will be presented at a medical meeting in 2025.
“Treatment goals for patients with PNH have greatly evolved, and we can now aim to resolve signs and symptoms of disease in most patients,” said Risitano, who is also chair of the International PNH Interest Group. “It is promising to see this evolution, and we will continue to make progress to best support these patients.”
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