In Phase 3 studies, Fabhalta eases fatigue, improves life quality in PNH
Treatment was tested in APPLY-PNH and APPOINT-PNH
Treatment with Fabhalta (iptacopan) can ease fatigue and improve quality of life for people with paroxysmal nocturnal hemoglobinuria (PNH), according to data from two Phase 3 clinical trials.
“These results … indicate that [Fabhalta] results in clinically meaningful disease control and meaningful improvements in the fatigue and [health-related quality of life] impacts of PNH,” the researchers wrote. The study, “Patient-reported improvements in paroxysmal nocturnal hemoglobinuria treated with iptacopan from 2 phase 3 studies,” was published in Blood Advances. The work was funded by Novartis, which sells Fabhalta.
In PNH, part of the immune system called the complement cascade becomes overactive and destroys blood cells, leading to anemia, or low red blood cell counts, which can cause fatigue and other symptoms. Fabhalta is an oral treatment approved in the U.S. for PNH that blocks the activity of a complement protein called factor B. Its approval was based on data from two Phase 3 clinical trials. One, APPLY-PNH (NCT04558918), enrolled people with PNH whose disease wasn’t well controlled with Soliris (eculizumab) or Ultomiris (ravulizumab), both of which are approved PNH treatments that target C5, another complement protein. Participants in APPLY-PNH were randomly assigned to continue treatment with a C5 inhibitor or switch to Fabhalta for about six months.
The other study, APPOINT-PNH (NCT04820530), enrolled people with PNH who hadn’t been treated with a complement inhibitor. All the patients in APPOINT-PNH were treated with Fabhalta.
The main goal of both studies was to assess how well Fabhalta could increase hemoglobin, the protein inside red blood cells that’s responsible for oxygen transport, indicating easing anemia. Results from both showed that most patients given Fabhalta saw meaningful hemoglobin increases.
Fatigue, quality of life assessed
The studies included patient-reported measures of disease severity. A standardized tool called the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) was used to assess changes in fatigue, while one called the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) evaluated quality of life. Here, researchers reported on the outcomes from these measures.
“The FACIT-Fatigue and EORTC QLQ-C30 are considered relevant for assessing PNH-associated fatigue and [health-related quality of life], respectively, and both have been used extensively in clinical trials and by the International PNH Registry to evaluate quality of life in patients with PNH,” the researchers wrote.
Based on standard cutoffs, more than half the patients given Fabhalta in both trials saw clinically meaningful easing of fatigue, based on FACIT-Fatigue scores. By contrast, this was seen in 11% of those who continued on C5 inhibitors in APPLY-PNH.
There was also a correlation between changes in hemoglobin and FACIT-Fatigue scores. In other words, those whose anemia was reduced by treatment were more likely to report lower fatigue severity.
The EORTC QLQ-C30 includes subscales that measure different aspects of quality of life, including physical functioning; role functioning, that is, how well a person performs their day-to-day responsibilities and activities; fatigue; and shortness of breath. Across both studies, roughly 4 out of 10 patients on Fabhalta saw clinically meaningful improvements in physical functioning and role functioning, and about half had clinically meaningful improvements in fatigue and shortness of breath.
In APPLY-PNH, the patients given Fabhalta were two to four times more likely to have clinical improvements in EORTC QLQ-C30 subscales than those who stayed on C5 inhibitors.
Collectively, the data suggest those given Fabhalta had “unequivocal improvement in overall quality of life after treatment,” wrote the researchers, who noted the data “provide evidence of an additional treatment benefit with [Fabhalta] compared with [C5 inhibitors], with respect to increasing the proportion of patients who experience meaningful improvement in [health-related quality of life].”
The analysis was limited by its small size; across both trials there were fewer than 150 participants, the researchers said. The studies were also open-label, meaning the participants knew what treatment they were receiving, so the impact of the placebo effect on the results couldn’t be ruled out.
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