Real-world study: Ultomiris is preferred treatment option for PNH
Newer therapy found safe, effective for Italian patients previously on Soliris
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Use of the approved therapy Ultomiris (ravulizumab) keeps hemolysis, or the destruction of red blood cells, under control, reduces the need for transfusions, and is generally well tolerated for people with paroxysmal nocturnal hemoglobinuria (PNH), a real-world study in Italy has found.
According to the researchers, the benefits seen with the drug’s use make it a convenient and preferred treatment option for individuals with PNH who were previously on the older therapy Soliris (eculizumab). Both treatments are given via intravenous, or into-the-vein, infusions, but Ultomiris is designed to last longer in the body, meaning it requires fewer infusions than does Soliris.
“Switching patients with PNH from [Soliris] to [Ultomiris] is effective and safe,” the researchers wrote. “Patients’ preference indicated [Ultomiris] as the favorite treatment.”
The study, titled “Real life use of ravulizumab in Italian patients with paroxysmal nocturnal hemoglobinuria: evidence from the REACTION observational study,” was published in the Annals of Hematology. The work was funded by Alexion Pharmaceuticals, now part of AstraZeneca, which markets both Ultomiris and Soliris.
In PNH, red blood cells are missing protective surface proteins that signal to the immune system that they are normal and should not be attacked. Without these protective proteins, a component of the immune system called the complement system mistakenly destroys the red blood cells — a process known as hemolysis.
Ultomiris inhibits a complement protein called C5, preventing hemolysis and helping ease symptoms of PNH.
REACTION study tracked patients switching from old to new therapy
The observational REACTION study (NCT05274633), completed last year, involved 81 patients who had previously received Soliris, an earlier complement inhibitor also approved for PNH. The main goal was to see how well Ultomiris controlled hemolysis, which was measured by lactate dehydrogenase (LDH), an enzyme released when red blood cells are destroyed.
Compared with Soliris, Ultomiris is a second-generation inhibitor designed to work longer and maintain hemolysis control with fewer treatments.
All study participants were adults diagnosed with PNH who had received Soliris every two weeks for a median of 6.1 years. Slightly more than half of the patients were women, and about two-thirds overall experienced no symptoms. Among those who did, fatigue was the most common, affecting nearly one-quarter.
Ultomiris was infused every eight weeks for a median of nearly one year. Altogether, two patients discontinued treatment, and none switched back to Soliris.
By the end of the study, median LDH levels had decreased by 2.6%, showing that Ultomiris effectively controlled hemolysis. Most patients (92%) had LDH within normal limits, or less than 1.5 times the upper limit.
“The change was consistent during the study observation period, showing hemolysis control during the [Soliris] treatment period and after the switch to [Ultomiris],” the researchers wrote.
5 patients became transfusion-free after switching to Ultomiris
The proportion of patients who required transfusions was significantly higher with Soliris than with Ultomiris (25% vs. 18.8%). Five patients who needed transfusions on Soliris were transfusion-free after switching to Ultomiris. Transfusions were mainly due to hemolysis or aplastic anemia, which occurs when the bone marrow stops producing blood cells.
Quality of life was measured using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue questionnaires. Scores remained stable over one year of follow-up, indicating patients maintained normal daily functioning.
Patients said they preferred Ultomiris over Soliris, citing fewer infusions and more flexibility for activities, according to the researchers.
The REACTION study confirmed the effectiveness of [Ultomiris] in maintaining stable disease and [red blood cell destruction] control in the real-world setting. … In addition, [Ultomiris] was the [patients’] preferred choice of treatment, mainly for its convenience of administration.
One-third of patients reported mild to moderate side effects, mostly reactions at the infusion site, fever, fatigue, and infections. Four patients (5%) experienced serious side effects, with one serious infection considered related to Ultomiris, “showing a safety profile more favorable than the one observed in the clinical trials,” the researchers wrote. The team noted that, overall, the occurrence of adverse events among patients “appears to decrease over time.”
Based on these findings, the researchers suggested that Ultomiris can safely replace Soliris for use in the real world.
“The REACTION study confirmed the effectiveness of [Ultomiris] in maintaining stable disease and hemolysis control in the real-world setting,” the team wrote. “In addition, [Ultomiris] was the [patients’] preferred choice of treatment, mainly for its convenience of administration.”
