Switch to Empaveli shows good efficacy in real-world Italian study
Need for transfusions reduced for PNH patients switching to newer therapy
People with paroxysmal nocturnal hemoglobinuria (PNH) who switch to Empaveli (pegcetacoplan) after having an inadequate response to other, older treatments usually see good efficacy with the newer therapy, according to a study that looked at real-world data in Italy.
Indeed, according to the researchers, “most patients exhibited a complete or good response,” with less need for blood transfusions. None of the individuals who switched experience thrombosis, when a blood clot blocks a blood vessel.
“This report confirms the significant improvements in [hemoglobin] and, consistently, the reduction of transfusion need over the course of [Empaveli] therapy in a real-world series,” the researchers wrote, noting that “77% of patients [were] transfusion free at data cut-off.”
The study, “Real-world evidence of pegcetacoplan in patients with paroxysmal nocturnal haemoglobinuria: A nationwide Italian study,” was published as a letter to the editor in the British Journal of Haematology.
22 patients with poor treatment response switched to Empaveli
In PNH, part of the immune system called the complement cascade becomes abnormally activated, resulting in red blood cell destruction, known as hemolysis, and reduced levels of hemoglobin — the protein that red blood cells use to carry oxygen through the bloodstream.
The complement cascade works like a series of dominoes falling: one protein activates another, which activates others, and so on. The first PNH treatments to win widespread approval, Soliris (eculizumab) and Ultomiris (ravulizumab), both work to block complement activation by targeting a complement protein called C5.
Empaveli is a newer therapy that blocks complement activation by targeting C3, a different complement protein that acts upstream, or before, C5 in the complement cascade. It is approved for adults with PNH in the U.S. and Europe, where it is marketed as Aspaveli.
In this report, scientists described the experiences of 22 Italian people with PNH, all adults, who switched to Empaveli after having a suboptimal response to treatment with Soliris or Ultomiris.
Based on standard criteria, all of the patients were judged to have had either no response, a minor response, or a partial response to C5-targeting treatments.
In the year before switching treatments, more than half of the patients had experienced at least one episode of breakthrough hemolysis, in which symptoms associated with blood cell destruction reappear despite treatment. In most cases, these episodes required blood transfusions, with slightly more than 10% leading to hospitalization.
These results highlight that, over time, most patients either maintained or improved their response to [Empaveli], with complete or good responses remaining the most common outcomes.
Within two months of switching to Empaveli, 54.5% of the patients had a complete response, essentially meaning that their disease was fully under control. All but one of the remaining patients had a good response to treatment. At six months after starting Empaveli, all but one of the patients still had a response judged as either complete or good.
“These results highlight that, over time, most patients either maintained or improved their response to [Empaveli], with complete or good responses remaining the most common outcomes,” the researchers wrote.
No unexpected safety issues documented in real-world study
Four of the patients discontinued Empaveli after a median of 16 months, or 1.3 years. One stopped treatment due to side effects, primarily injection reactions and headache. One discontinued the therapy due to pregnancy, while another stopped due to undergoing a stem cell transplant. A final patient stopped the therapy because it was no longer controlling the disease after more than two years of treatment.
Six individuals, or 27% of the patients, experienced an episode of breakthrough hemolysis while on Empaveli. One of these events required hospitalization and four required blood transfusions.
Also, the researchers noted, median levels of hemoglobin increased markedly after patients switched to Empaveli. Meanwhile, levels of lactate dehydrogenase, a marker of hemolysis, decreased.
No unexpected safety issues were documented in the report.
“While some [breakthrough hemolysis] events and transfusion dependency remained in a minority of patients, the overall risk-benefit profile was [favorable], with no new significant safety concerns,” the researchers wrote.
These data suggest that Empaveli “is a highly effective treatment option for patients with PNH who remain [anemic, with too few red blood cells carrying oxygen throughout the body] after treatment with anti-C5 inhibitors,” the team wrote.
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