Extravascular hemolysis affects PNH patients on Soliris, Ultomiris
Significant red blood cell destruction outside blood vessels found in up to 25%
Up to 1 in 4 people with paroxysmal nocturnal hemoglobinuria (PNH) who are treated with Ultomiris (ravulizumab-cwvz) or Soliris (eculizumab) experience clinically significant extravascular hemolysis — the destruction of red blood cells — but this isn’t typically associated with severe fatigue, a new global study reported.
Soliris and Ultomiris are both approved treatments for PNH that work by targeting a protein in the body known as C5, with an aim of inhibiting red blood cell destruction.
“The findings of this post-hoc analysis show that, after C5 inhibitor treatment, [clinically significant extravascular hemolysis] affected [20% to 25%] of patients receiving PNH treatment, and had a similar prevalence among patients receiving [Ultomiris] or [Soliris],” the researchers wrote.
The study, “Characterizing clinically significant extravascular hemolysis in adults with PNH on ravulizumab or eculizumab treatment,” was published in the journal Blood Advances. The majority of the authors have received funding or have ties to the companies backing the study.
Finding out how common is extravascular hemolysis
In PNH, part of the immune system called the complement cascade becomes abnormally activated, leading to the destruction of blood cells. The destruction of red blood cells, also known as hemolysis, can occur inside blood vessels, when it’s known as intravascular hemolysis, or outside blood vessels, which is called extravascular hemolysis.
Soliris and Ultomiris both are given by intravenous, or into-the-vein, infusion as a treatment for PNH. However, Ultomiris is designed to be longer lasting in the body, meaning it needs to be administered less frequently than Soliris.
Both medications are generally effective at controlling intravascular hemolysis, but aren’t always effective at managing extravascular hemolysis, data have shown.
Moreover, scant data are available on how common it is for people with PNH who are on these medications to have uncontrolled clinically significant extravascular hemolysis.
Initial approvals of Ultomiris were based on data from two Phase 3 clinical trials. The first, ALXN1210-PNH-301 (NCT02946463), launched in 2016 and tested Soliris and Ultomiris in people with PNH who had never been treated with a C5 inhibitor. The second, ALXN1210-PNH-302 (NCT03056040), started the following year and evaluated the two therapies in PNH patients who had previously been on Soliris and were clinically stable.
Both studies showed that Ultomiris and Soliris are similarly effective at controlling hemolysis in PNH.
Overall, these results show that the C5 inhibitors [Soliris and Ultomiris] provide benefit to adults with PNH with [clinically significant extravascular hemolysis.
In this study, scientists examined data from these two trials hoping to better understand how common extravascular hemolysis is in PNH patients on Soliris or Ultomiris.
The team found that, across the two trials, 20% to 25% of patients treated with either therapy experienced clinically significant extravascular hemolysis, as determined by lab tests measuring the levels of hemoglobin and the number of reticulocytes in the blood. Hemoglobin is the oxygen-carrying protein in red blood cells; low hemoglobin levels indicate the presence of anemia. Reticulocytes are immature red blood cells; high reticulocyte counts are an indication of excessive hemolysis.
One of the most common symptoms of uncontrolled clinically significant extravascular hemolysis in PNH is fatigue. All of the evaluable trial participants who experienced extravascular hemolysis reported some fatigue. Fatigue severity was rated as mild or moderate in almost all cases. Researchers noted that the levels of fatigue seen in these patients were similar to those seen in people of the general population. Measures of life quality and fatigue severity remained generally stable over time.
“In patients with [clinically significant extravascular hemolysis], fatigue remained close to levels in the general population during treatment,” the researchers wrote. “Overall, these results show that the C5 inhibitors [Soliris and Ultomiris] provide benefit to adults with PNH with [clinically significant extravascular hemolysis].”
About the Author
