Real-world data support Ultomiris for first-line PNH treatment
Study: Drug maintained disease control for up to two years of follow-up
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Treatment with Ultomiris (ravulizumab) safely helps maintain or achieve disease control in people with paroxysmal nocturnal hemoglobinuria (PNH), according to a real-world study involving more than 200 adults.
Among that group, people who switched from the older therapy, Soliris (eculizumab), to Ultomiris maintained disease control for up to two years of follow-up. Among those who started Ultomiris as their first complement inhibitor, treatment brought hemolysis — the destruction of red blood cells — under control within six months and reduced the need for blood transfusions within one year. Overall, the therapy showed a favorable safety profile.
While both therapies are given via intravenous (into-the-vein) infusions, Ultomiris requires fewer infusions than Soliris. The findings, while also confirming “the effectiveness and safety of [Ultomiris] in the real-world setting,” further support its use “as the first-line treatment of choice for patients with PNH, where available,” researchers wrote.
The study, “Real-World Effectiveness and Safety of Ravulizumab in Patients With Paroxysmal Nocturnal Hemoglobinuria: Evidence From the International PNH Registry,” was published in the American Journal of Hematology. It was funded by Alexion Pharmaceuticals, now part of Astrazeneca, which markets both Ultomiris and Soliris. Two of the study’s nine authors work for Alexion.
Ultomiris, Soliris work by blocking key complement protein
In PNH, red blood cells lack protective surface proteins that signal to the immune system they are healthy. Without these proteins, a part of the immune system called the complement system mistakenly attacks and destroys them in a process known as hemolysis. PNH symptoms include anemia (low red blood cell count), fatigue, and shortness of breath.
Soliris and Ultomiris are two PNH treatments that work by blocking a complement protein called C5, preventing hemolysis and helping ease disease symptoms. However, Ultomiris lasts longer in the body and is given every eight weeks, compared with every two weeks for Soliris.
Previous clinical trials and real-world analysis have shown that Ultomiris is as effective as Soliris in controlling hemolysis, demonstrating long-term safety and efficacy for up to six years, with the added convenience of less frequent dosing.
In this study, an international team of researchers evaluated Ultomiris in people with PNH who had never received a complement inhibitor before starting the therapy, as well as in those who switched from Soliris. They also examined patients’ demographic and clinical characteristics at the start of treatment.
The analysis included 226 people with PNH enrolled in the International PNH Registry (NCT01374360), a large global observational study that collects real-world data from people with PNH. Of these, 203 had previously been treated with Soliris, while 23 had not received any complement inhibitor therapy before starting Ultomiris.
Need for red blood cell transfusions decreased with Ultomiris treatment
At the start of treatment, participants new to complement therapy were more likely to be female (69.6% vs. 50.2%), Asian (47.8% vs. 23.2%), and to have a history of bone marrow disorders (59.1% vs. 40.8%) than those who had previously been treated with Soliris. They also had more active disease, with elevated levels of lactate dehydrogenase (LDH), a marker of hemolysis, indicating ongoing red blood cell destruction, compared with those previously treated with Soliris, whose LDH levels were already near normal.
A larger part of those previously treated with Soliris was European (65.5% vs. 39.1%) and white (68.8% vs. 47.8%). They had lived with PNH for longer (12.8 vs. 5.7 years) and were more likely to have a history of blood clot-related complications (18.8% vs. 8.7%).
Among participants who had previously received Soliris, disease control was maintained during Ultomiris treatment, with stable levels of LDH, hemoglobin (a marker of anemia), and kidney function over up to two years of follow-up.
In those who had not previously received complement inhibitor, LDH levels dropped to near-normal levels within six months, and continued to decrease over two years of follow-up. Hemoglobin levels and kidney function also improved early in treatment and were maintained over time.
This study provides new evidence that, in a real-world population, improvements in clinical outcomes with [Soliris] are maintained with [Ultomiris].
The need for red blood cell transfusions decreased with Ultomiris treatment, particularly among those new to therapy. In this group, the proportion of individuals requiring transfusions dropped from 39.1% in the year before treatment to about 21.7% in the year after starting Ultomiris, along with a substantial reduction in the number of transfusions.
Among participants who switched from Soliris, transfusion needs were already low and remained largely stable.
In total, 11 previously treated participants (5.4%) and two (8.7%) who had not received prior complement inhibitors discontinued Ultomiris. Reasons included switching to another complement inhibitor, switching back to Soliris, or lack of effectiveness.
Overall, the number and rate of major adverse vascular events, including blood clot-related complications, declined after starting Ultomiris. No meningococcal infections, a known risk of complement inhibitors, were reported. One death occurred in a previously treated patient, but it was not related to Ultomiris. No deaths were reported in the treatment-naive group.
“This study provides new evidence that, in a real-world population, improvements in clinical outcomes with [Soliris] are maintained with [Ultomiris],” the researchers concluded. “This analysis provides the largest real-world dataset to date on [Ultomiris] in PNH, reinforcing its effectiveness and safety across diverse patient populations and supporting its continued use in clinical practice as the first line treatment of choice, where available.”
