Andrea Lobo, PhD - Science Writer

Treatment with Empaveli (pegcetacoplan) — a C3 protein blocker — effectively improved disease control and health-related quality of life, while reducing fatigue in people with paroxysmal nocturnal hemoglobinuria (PNH) in the U.S. and Europe, a real-world study reported. Study findings also showed higher physician and patient satisfaction with Empaveli than with standard-of-care treatment with the C5 inhibitors Soliris (eculizumab) or Ultomiris (ravulizumab). Both C3 and C5 proteins are components of the complement cascade, a part of the immune system that helps the body fight off infections. Their activation is associated with the destruction of red blood cells (hemolysis) both inside and outside of blood vessels, common PNH hallmarks. “This first real-world study demonstrates that [Empaveli] provides an important treatment option for patients with PNH, particularly those who do not respond as hoped to C5 [inhibitors] treatment,” the researchers wrote. The study, “Pegcetacoplan in paroxysmal nocturnal haemoglobinuria: Its use, its clinical effectiveness, and its influence on health-related quality of life and productivity,” was published in the European Journal of Haematology. Empavli works to treat PNH by blocking C3, a complement cascade protein. PNH is usually caused by mutations in the PIGA gene affecting stem cells that give rise to all blood cells. The disease is characterized by the destruction of blood cells, particularly red blood cells, which are responsible for transporting oxygen throughout the body. Empaveli, sold as Aspaveli in Europe, blocks the activation of the complement cascade protein C3. The complement cascade comprises several proteins that work together. The C3 protein normally splits into C3a and C3b; C3b prompts hemolysis outside blood vessels. This subunit also activates the C5 complement protein, which also splits into C5a and C5b, involved in hemolysis inside blood vessels. Empaveli prevents C3 protein splitting, therefore helping to stopping hemolysis both inside and outside blood vessels. "By inhibiting C3 instead of C5, [Empaveli prevents] complement activation further upstream," the researchers wrote. Empaveli was approved in the U.S. to treat adults with PNH in May 2021, and later that year in the European Union for adults who are anemic after at least three months of treatment with a C5 inhibitor To learn more about Empaveli's real-world use and efficacy, the scientists analyzed data from PNH patients being treated with Empaveli for at least one month (range, 1.3 to 14.8 months). Data were obtained from an independent group working in the U.S. and several European countries and reporting physician and patient perceptions of the treatment: the Adelphi Real World PNH Disease Specific Programme. Views of 14 physicians in 5 countries and up to 61 of their patients. A total of 14 physicians provided information covering 61 of their patients (37 in the U.S.; 24 in France, Germany, Spain and Italy) diagnosed with PNH between nine months to 18 years earlier; most patients were male (59%) with a mean age of 37.1 years. The physicians considered the patients’ disease to be well or very well controlled at the time of data collection. According to the physicians, treatment with Empaveli was chosen mainly to "improve hemoglobin [the protein that transports oxygen in red blood cell] levels," "reduce fatigue," or "control hemolysis," symptoms reported for more than 50% of the patients. In Europe, physicians specifically reported wanting to "improve life expectancy/survival" and "improve LDH [lactate dehydrogenase] levels" for more than 50% of the patients. High blood levels of LDH are associated with hemolysis or tissue damage. All patients received 1,080 mg doses of Empaveli by subcutaneous (under-the-skin) injection, with 98% treated twice weekly. A majority (90%) had switched from a C5 inhibitor to Empaveli. Compared to treatment initiation, hemoglobin levels at the time of data collection were 2.5 g/dL higher on average (9 to 11.5 g/dL). The proportion of patients with LDH levels at least 1.5 times higher than the normal upper limit fell by 27.4%. Both physician- and patient-reported satisfaction was higher with Empaveli than with a previously prescribed C5 complement inhibitor for 91.1% of the 56 patients who switched. Among physicians, higher satisfaction was mainly related to improved disease control, while among patients it mostly linked with lower fatigue levels. Physician-perceived fatigue also was lower with Empaveli's use. They reported that around 80% of their patients were considered to have moderate or severe fatigue at treatment initiation, and more than 80% to have no or low fatigue following treatment. “In our study, fatigue appeared to be ameliorated in patients receiving PEG in real-world clinical settings. This is of clinical importance as fatigue has been identified as one of the most burdensome symptoms of PNH, persisting in patients receiving C5 [inhibitors],” the researchers wrote. Physicians also considered that health-related quality of life improved with Empaveli's use. Overall, these “findings are the first to establish the real-world effectiveness of [Empaveli] collectively in the United States and EU, providing [important] evidence that the response to this novel treatment for PNH in clinical practice is in-line with findings from clinical trials,” the team wrote. Further research should investigate how outcomes vary with treatment duration to fully understand the real-world benefits of Empaveli for people with PNH. Five of the study's 13 authors are affiliated with Sobi or Apellis Pharmaceuticals, the developers of Empaveli. Both companies subscribe to the Adelphi program's reports.

Andrea Lobo, PhD, —

Articles by Andrea Lobo

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