PNH patients show five times lower mortality risk with Ultomiris
Long-term treatment tended to erase blood transfusion need, boost life quality
Long-term treatment with Ultomiris (ravulizumab) reduced the risk of death by five times in people with paroxysmal nocturnal hemoglobinuria (PNH), and also tended to eliminate the need for blood transfusions and to improve patients’ quality of life, a new analysis suggests.
The findings were detailed in the study, “Ravulizumab demonstrates long-term efficacy, safety and favorable patient survival in patients with paroxysmal nocturnal hemoglobinuria,” which was published in the Annals of Hematology. The work was funded by Alexion, AstraZeneca Rare Disease, which markets Ultomiris.
In PNH, a part of the immune system called the complement cascade becomes abnormally activated, leading to the destruction of blood cells. Ultomiris is a widely approved PNH treatment that dampens the complement cascade’s activity. Its approvals for PNH were based mainly on data from two Phase 3 clinical trials. ALXN1210-PNH-301 (NCT02946463) tested the therapy against a placebo in PNH patients who’d never been given a complement-inhibiting treatment, while ALXN1210-PNH-302 (NCT03056040) tested it against Soliris (eculizumab), a previously approved PNH therapy that works in a similar way, in patients who were clinically stable after receiving Soliris.
After about six months, the participants in both studies were able to join an open-label extension where all were treated with Ultomiris and monitored for long-term outcomes. The study included data on more than 400 patients who were on Ultomiris for up to six years.
“With up to [six] years of treatment follow-up in over 400 patients with PNH … this publication reports the longest and largest dataset of [Ultomiris] treatment outcomes in patients with PNH,” the researchers wrote.
Eleven patients died during the study, with infections, cancer, and heart attacks among the causes of death. Only one death was considered related to Ultomiris treatment.
To put the number of deaths into context, the researchers compared the outcomes of PNH patients who’d never received a complement inhibitor before Ultomiris against data from hundreds of untreated PNH patients tracked as part of the International PNH Registry (NCT01374360). The results indicated the risk of death over four years was five times lower among patients treated with Ultomiris.
Outcomes with Ultomiris treatment
One of the most common life-threatening complications of PNH are vascular events, such as blood clots that block blood flow. Throughout the follow-up, fewer than 5% of patients had vascular events. The rate of these events was somewhat lower in those who’d previously been on Soliris, implying the risk is reduced with long-term complement-inhibiting treatment.
Breakthrough hemolysis, which is red blood cell destruction despite treatment, was reported in 7.8% of patients who’d previously been on Soliris and 14.8% of those who hadn’t taken a complement-blocking therapy before Ultomiris. In some cases, breakthrough hemolysis was associated with events that carry a risk of increased complement activity, such as infection or surgery.
More than half the patients didn’t require any blood transfusions over years of treatment with Ultomiris. The proportion of patients who didn’t need blood transfusions during that time was somewhat higher among those who’d previously been on Soliris, again suggesting the benefit of long-term treatment with complement-blocking therapies.
Patient-reported measures suggested quality of life tended to improve once patients started on Ultomiris, regardless of whether they’d been on Soliris previously. Over several years on Ultomiris, patients tended to have life quality scores that were comparable to those of people who don’t have PNH, the researchers said.
Safety data were generally consistent with what’s already known about Ultomiris’ safety profile. About a third of the patients had treatment-related side effects, which were serious in 5% of them. Less than 3% stopped taking Ultomiris due to side effects.
“These long-term results further add to the body of evidence supporting the use of [Ultomiris] as the first-line, long-term treatment of choice for patients with PNH, where available, offering patients with PNH immediate, complete, and sustained inhibition of terminal complement-mediated activity,” the researchers wrote.
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