Empaveli may benefit patients with impaired bone marrow function
Improvements seen for some PNH adults in 2 Phase 3 trials: Analysis
Treatment with Empaveli (pegcetacoplan), approved for adults with paroxysmal nocturnal hemoglobinuria (PNH), may lead to clinically meaningful improvements in blood parameters and fatigue among those with impaired bone marrow function.
That’s according to a new analysis of data from two Phase 3 clinical trials — PEGASUS (NCT03500549) and PRINCE (NCT04085601) — that assessed the safety and efficacy of Empaveli in people with PNH.
“Across both [the] PEGASUS and PRINCE studies, [Empaveli] treatment was associated with improvements in haematological [blood-related] and clinical parameters regardless of bone marrow function status,” the researchers wrote. “Thus, even patients with impaired bone marrow function may achieve clinically meaningful improvements with [Empaveli].”
The study, “Moving toward Individual Treatment Goals with Pegcetacoplan in Patients with PNH and Impaired Bone Marrow Function,” was published in the International Journal of Molecular Sciences.
Empaveli indicated for reducing red blood cell destruction in PNH
PNH is mainly characterized by the abnormal activation of the complement cascade, a part of the immune system, which leads to the destruction of red blood cells, or hemolysis. Symptoms may include anemia, or low red blood cell counts, fatigue, and bone marrow-related problems, including impairments in the production of new blood cells.
A complement inhibitor therapy, Empaveli can be used in PNH patients to reduce hemolysis occurring both inside and outside blood vessels.
In both PEGASUS and PRINCE, treatment with Empaveli significantly increased the levels of hemoglobin — the oxygen-carrying protein in red blood cells — and lowered the levels of reticulocytes, or immature red blood cells, and lactate dehydrogenase, a marker of hemolysis.
Empaveli treatment also reduced the need for blood transfusions among patients, and eased fatigue, as assessed by the Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score. FACIT-Fatigue is a patient-reported measure in which higher scores indicate less fatigue.
Individuals with overt bone marrow dysfunction were excluded from the two trials. However, a subset of patients in both studies showed signs of impaired bone marrow function, despite not meeting the criteria for overt bone marrow dysfunction.
Here, the researchers conducted an analysis to assess the clinical response of PNH patients showing signs of bone marrow dysfunction who were treated with Empaveli in PEGASUS or PRINCE. The PEGASUS trial compared the efficacy of Empaveli to that of Soliris (eculizumab), another approved PNH treatment, while the PRINCE study assessed the effects of Empaveli in comparison with standard of care in patients not previously treated with complement inhibitors.
In this analysis, bone marrow dysfunction was defined as having hemoglobin levels below 10 g/dL and a total neutrophil count below 1.5 billion cells/L. Neutrophils are a type of immune cell. The analysis specifically included five Empaveli-treated patients who participated in PEGASUS and seven who took part in PRINCE.
Treatment seen to achieve hemoglobin normalization for some patients
The results showed that after 16 weeks, or about four months, of treatment with Empaveli, one patient in PEGASUS achieved hemoglobin normalization. Three patients in PRINCE also did so after 26 weeks, or about six months. Further, three patients in PEGASUS and four in PRINCE also saw their LDH, neutrophil, and reticulocyte levels normalize. Fatigue also eased in two patients in each trial.
Importantly, none of the patients with bone marrow dysfunction treated with Soliris in PEGASUS or with supportive care in PRINCE reached normal hemoglobin levels.
In general, however, the proportion of patients with impaired bone marrow function achieving a normalization of blood parameters was lower than that of patients with normal bone marrow function across the two studies, according to the researchers.
“While a smaller proportion of patients with impaired bone marrow function were able to achieve normalisation of [hemoglobin], LDH, [reticulocyte], neutrophil and platelet count, as well as FACIT-Fatigue scores, this is likely not treatment-related but rather due to the impaired bone marrow function,” the team wrote.
Considering indicators of a patient’s bone marrow function may be a more appropriate and beneficial approach to setting [individualized] treatment goals and evaluating PNH-targeted treatment success in the future.
Next, the researchers reanalyzed the data considering clinically relevant changes rather than normalization. Specifically, they looked for an increase of 2 g/dL or more in hemoglobin, a reduction to at least 1.5 times the upper limit of normal in LDH, and an increase of at least five points in fatigue scores.
Using these new parameters, a higher proportion of patients showed an increase in hemoglobin levels, as well as a reduction in LDH levels and fatigue.
“Overall, improvements in [blood] and clinical parameters were seen in patients receiving [Empaveli] treatment with or without impaired bone marrow function,” the researchers wrote, noting that “patients with impaired bone marrow function may benefit” from treatment with Empaveli.
“Considering indicators of a patient’s bone marrow function may be a more appropriate and beneficial approach to setting [individualized] treatment goals and evaluating PNH-targeted treatment success in the future,” the team concluded.
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