The incidence of injection site reactions (ISRs) in patients with paroxysmal nocturnal hemoglobinuria (PNH) treated with pegcetacoplan (PEG) is similar to that reported for comparable therapies, according to a study comparing ISR safety outcomes from the phase 3 PEGASUS trial to ISR incidences from similarly administered treatments based on published literature.
“Management strategies for ISRs with these drugs [drugs delivered similarly to PEG] may potentially be useful for reactions observed with PEG,” the study’s authors concluded. Such strategies included injection site rotation and empowering patients to gain confidence and experience in self-administration through training by healthcare providers.
Data from the PEGASUS trial showed that ISRs observed with PEG treatment were mostly mild and decreased over time.
Most ISRs occurred during the run-in period (58%), followed by the randomized combination period (PEG arm, 36.6%; eculizumab arm, 2.6%) and the open-label period (PEG arm, 18%; eculizumab arm, 28%).
Read more about PNH therapies
Moreover, the proportion of moderate ISRs was 2.5% in the run-in period, 2.4% (PEG arm) and 0% (eculizumab arm) in the randomized combination period, and 2.6% in the open-label period (for both PEG arm and eculizumab arm). No ISRs were severe or led to study drug discontinuation.
The researchers identified 5 therapies as comparable to PEG (ie, subcutaneously administered, having 10 mL or greater injection volume or PEGylated): immunoglobulin with hyaluronidase, deferoxamine, daratumumab and hyaluronidase, certolizumab pegol, and pegfilgrastim. The incidence of ISRs with these therapies varied from 5% to 67% and were generally mild.
The PEGASUS trial (NCT03500549) was designed to evaluate the efficacy and safety of PEG in patients with PNH. Participants completed a 4-week run-in period with eculizumab plus PEG and were then randomized to PEG (n=41) or eculizumab monotherapy (n=39). Participants receiving eculizumab during the randomized combination period entered another 4-week run-in period (eculizumab plus PEG), followed by an open-label period in which all participants received PEG monotherapy.
The primary endpoint was change from baseline in hemoglobin to week 16. Secondary objectives included safety, namely monitoring treatment-emergent adverse events and ISR incidence.
PEG is a C3-complement inhibitor that has been approved by the US Food and Drug Administration for the treatment of PNH. It is self-administered twice weekly via 2 subcutaneous injections of 10 mL at 2 distinct sites.
Reference
Sharma V, Weitz I, Koprivnikar J, et al. Injection-site reactions at week 48 in the randomized phase 3 PEGASUS trial of pegcetacoplan compared with eculizumab for individuals with paroxysmal nocturnal hemoglobinuria. Presented at: the European Hematology Association (EHA) annual congress, Frankfurt, Germany; June 8-11, 2023.
