Pegcetacoplan in paroxysmal nocturnal hemoglobinuria: A systematic review on efficacy and safety

Abstract

Introduction: Pegcetacoplan, a pegylated penta-decapeptide, targets complement C3 to control both intravascular and extravascular hemolysis. This systematic review aims to study the efficacy and safety of pegcetacoplan in paroxysmal nocturnal hemoglobinuria (PNH). Methods:We performed a comprehensive and systematic literature search for all studies on PubMed, Google Scholar, Cochrane Library, and clini caltr ials.gov. The studies were searched using keywords "paroxysmal nocturnal hemoglobinuria" or "PNH," "Pegcetacoplan" or "Empaveli." The primary outcomes included change in hemoglobin level, transfusion independence, absolute reticulocyte count, and lactate dehydrogenase (LDH) level after pegcetacoplan therapy. The safety outcomes included the proportion of deaths and adverse effects. Results:We included a total of three studies. The total number of patients with PNH was112. 59.83% were female. In the PADDOCK study and study by Hillmen et al., the average increase in hemoglobin was 3.68 g/L and 2.37 g/L, respectively. In the study by de Castro et al., the hemoglobin level increased from below the lower limit of normal and stayed in the normal range (11.1-15.9 g/L). Absolute reticulocyte count and LDH levels decreased in all patients receiving pegcetacoplan. In the study by de Castro et al., LDH level remained stable, and within <1.5× upper limit of normal, whereas in the study by Hillman, the mean change of LDH from baseline was −15 ± 43 U/L. Two of six, seven of 23, and seven of 41 patients reported adverse events in the study by de Castro et al., PADDOCK, and Hillmen et al., respectively. Conclusion:Pegcetacoplan effectively improves hemoglobin level and transfusion requirements in patients with PNH, including those unresponsive to eculizumab.

Efficacy of complement inhibitors for patients with paroxysmal nocturnal hemoglobinuria: a systematic review and meta-analysis

“…While several systematic reviews have been conducted previously on complement inhibitors for PNH treatment, [16][17][18] they have focused on individual substances or provided a descriptive review of results from clinical trials. No systematic reviews, including those of ravulizumab, have been conducted.…”

“…While pivotal randomized clinical trials (RCTs) have been conducted to obtain regulatory approval for complement inhibitors, their sample sizes are relatively small, and the comparative efficacy data are restricted to a 26-week randomization period. [11][12][13][14][15] Although several systematic reviews on specific complement inhibitors exist, [16][17][18] a comprehensive analysis of short-and long-term efficacy data for all available treatments using unified criteria is still lacking. Considering that clinical trials of rare diseases have limited sample sizes, a comprehensive approach is required to establish optimal treatment strategies.…”

Injection Site Reactions with Long-Term Pegcetacoplan Use in Patients with Paroxysmal Nocturnal Hemoglobinuria: A Brief Report

“…Pegcetacoplan is a pegylated pentadecapeptide approved in the US for the treatment of adults with PNH and in the EU for adults with PNH and anemia despite receiving C5-targeted therapy for ≥ 3 months [ 5 – 7 ]. Pegcetacoplan binds to complement component C3 and its activation fragment C3b, thereby regulating downstream effectors of complement activation [ 8 ]. In the phase 3 PEGASUS trial (NCT03500549), pegcetacoplan was found to be superior to eculizumab in improving clinical and hematologic outcomes in patients with PNH previously treated with eculizumab and had a favorable safety profile with up to 48 weeks of treatment [ 7 , 9 ].…”