Empaveli eases fatigue, cuts need for transfusions in PNH: Review
Real-world data support treatment’s efficacy, researchers say
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Empaveli (pegcetacoplan) can ease disease burden for people with paroxysmal nocturnal hemoglobinuria (PNH), reducing signs of red blood cell destruction, lowering the need for blood transfusions, and improving fatigue and quality of life, according to a review of 12 studies conducted after Empaveli’s approval in 2021.
“These findings, based on studies including diverse patient populations and treatment settings, support generalizability and are broadly in line with the [Empaveli] clinical trial results,” the researchers wrote.
The study, ”Pegcetacoplan Delivers Real-World Therapeutic Benefits and Reduces Disease Burden for Patients With Paroxysmal Nocturnal Haemoglobinuria: A Systematic Literature Review of Pegcetacoplan Real-World Clinical and Patient-Reported Outcomes,” was published in the European Journal of Haematology.
PNH is a rare, acquired blood disorder marked by the destruction of red blood cells (hemolysis). Because red blood cells are vital for delivering oxygen throughout the body, people with PNH can experience a variety of symptoms, including fatigue and shortness of breath.
Empaveli, a subcutaneous (under-the-skin) injection, belongs to a class of PNH treatments called complement inhibitors. These medications block a part of the immune system called the complement cascade, a group of immune proteins in the blood that activate one another in a series of reactions.
Protein blocking
Several approved complement inhibitors, including Soliris (eculizumab), Ultomiris (ravulizumab-cwvz), and PiaSky (crovalimab-akkz), target the C5 protein, a component of the complement cascade, to prevent red blood cell destruction. But blocking this protein alone does not inhibit all arms of the complement cascade, and patients may continue to experience hemolysis.
Empaveli is designed to block the C3 protein, which acts earlier than C5 in the signaling chain and helping prevent more forms of hemolysis than C5 inhibition.
Empaveli was approved in the U.S., Europe, and several other regions in 2021 based on positive clinical trial results. Since then, several studies have examined how the therapy performs in routine clinical practice.
To assess those findings, researchers reviewed 12 real-world studies published or presented after Empaveli’s approval. The studies involved PNH patients from several countries and used a range of research methods.
Many of the studies evaluated laboratory markers associated with disease activity and hemolysis. Across the reports, treatment with Empaveli was generally associated with higher hemoglobin levels and reductions in lactate dehydrogenase (LDH) and absolute reticulocyte count (ARC), markers that reflect ongoing red blood cell destruction and the body’s efforts to replace the damaged cells.
The magnitude of these improvements varied among studies and depended on how long patients had been receiving treatment.
Five of the studies assessed how often participants needed blood transfusions, and found that patients generally required fewer transfusions after starting Empaveli. The largest drop was reported in a 2024 study in which 65.2% of participants required a blood transfusion six months before treatment initiation. That percentage dropped to 17.4% after six months of treatment.
While the researchers did not directly assess the effects of reduced transfusion dependence, they noted that fewer transfusions could lessen both healthcare costs and treatment burden.
“The implicit economic and humanistic costs of transfusions are not only minimized by the reduced need for the procedure itself, but also by the reduced risks of … transfusion-related adverse events,” the team wrote.
Several studies also evaluated outcomes reported by patients and physicians. Both groups indicated that treatment with Empaveli eased fatigue, while patients reported improvements in health-related quality of life.
One study asked participants and doctors about their satisfaction with Empaveli compared with previous treatment with a C5 inhibitor. Up to 91.1% of physicians and 90% of patients said they preferred Empaveli.
Together, the results support Empaveli as a safe and effective treatment for PNH in real-world settings. Despite differences in patient populations, study designs, and countries, improvements in laboratory markers, transfusion requirements, fatigue, and quality of life were generally consistent across studies, suggesting that Empaveli may be effective across many patient groups, the team concluded.
