Data confirm benefit of ravulizumab in patients with paroxysmal nocturnal hemoglobinuria
Key takeaways:
- Ravulizumab led to maintained control of intravascular hemolysis and sustained stable hemoglobin levels throughout the study period.
- Researchers observed no new adverse events with ravulizumab.
Data confirm the safety and efficacy of ravulizumab among patients with paroxysmal nocturnal hemoglobinuria previously treated with eculizumab, according to results of the REACTION study presented at ASH Annual Meeting and Exposition.
The findings showed that ravulizumab (Ultomiris, Alexion Pharmaceuticals) controlled intravascular hemolysis and sustained stable hemoglobin levels, researchers noted.
Assessing ‘the switch’
“Paroxysmal nocturnal hemoglobinuria [PNH] is a rare hematopoietic stem cell disorder characterized by uncontrolled terminal complement activation leading to hemolytic anemia, thrombosis, organ damage and premature mortality,” Bruno Fattizzo, MD, researcher in the hematology unit at Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy, and colleagues wrote. “In 2021, ravulizumab was approved in Italy as a treatment for PNH, but real-world evidence is currently lacking.”
For this reason, Fattizzo and colleagues conducted the multicenter, observational cohort REACTION study to examine the safety and efficacy of switching 80 patients (median age, 51.5 years; 48.8% men) with PNH who had received eculizumab (Soliris, Alexion Pharmaceuticals] for at least 26 weeks to ravulizumab across 28 centers in Italy.
Researchers collected efficacy and safety data at 52 and 26 weeks before “the switch,” at baseline (ie, the day of first ravulizumab dose), and then at 18, 34 and 52 weeks after the switch.
The percentage change in lactate dehydrogenase from baseline to the end of observation period during ravulizumab treatment at 52 weeks served as the primary outcome.
Fattizzo presented data from the final analysis on primary endpoints, breakthrough hemolysis event rate and transfusion need at 52 weeks of follow-up.
Data confirmed
Median time since PNH diagnosis was 9 years (interquartile range = 4.3-16.7). At baseline, 66.3% of patients had no comorbidities and 68.8%) had no symptoms of PNH.
Median duration of treatment with eculizumab was 6.1 years, at a median dose of 900 mg and median administration frequency of 14 days. Median duration of treatment with ravulizumab was 50 weeks at a median induction dose of 2,700 mg, followed by a median maintenance dose of 3,300 mg and median administration frequency of 56 days.
Researchers observed a median percentage change in lactate dehydrogenase from baseline to the end of the observation period of 2.7%, and median hemoglobin levels increased from 10.8 g/dL at baseline to 11.2 g/dL at the end of observation.
Moreover, the observed rate of breakthrough hemolysis events per 100 patient-years decreased from 6.3 during eculizumab treatment to 2.6 with ravulizumab.
Of note, researchers reported five breakthrough hemolysis events among two patients during the eculizumab treatment period compared with two among two patients during treatment with ravulizumab.
One quarter of patients required 108 packed red blood cell units during treatment with eculizumab compared with 20% of patients who required 67 packed red blood cell units during the ravulizumab treatment period.
Researchers observed no new adverse events. Two deaths occurred unrelated to ravulizumab.
“This is the first presentation of the REACTION study’s final results, that confirm the effectiveness and tolerability of switching patients with PNH from eculizumab to ravulizumab, as emerged from the phase 3 clinical trials,” Fattizzo and colleagues wrote.
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Fattizo B, et al. Abstract 2464. Presented at: ASH Annual Meeting and Exposition; Dec. 7-10, 2024; San Diego.