Pegcetacoplan (1) – Aspaveli®

• Clinical trials
  • The pharmaceutical manufacturer has submitted data from the completed, pivotal, multicentre, randomised, controlled, open-label Phase III PEGASUS trial for the benefit assessment.

Adults with paroxysmal nocturnal haemoglobinuria (PNH) who remain anaemic after at least 3 months’ treatment with a C5 inhibitor

• Consequently, a non-quantifiable additional benefit is identified for pegcetacoplan in the treatment of adult patients with PNH who remain anaemic after at least 3 months of treatment with a C5 inhibitor, as the scientific evidence does not permit quantification.
• The strength of the evidence is classified as ‘hint’.
• mortality
  • Overall survival was not assessed as an independent endpoint in the PEGASUS study. Deaths were recorded as part of the adverse event monitoring. No deaths occurred in any of the study arms during the RCP. The available data therefore show no relevant difference between the treatment arms.
• morbidity
  • Transfusion-free status
  • The endpoint ‘transfusion-free status’ during the RCP describes the proportion of patients who did not receive any transfusions (whole blood, red blood cell concentrates [RBCs] or other blood transfusions) between Day 1 and Week 16.
  • The results for the ‘transfusion-free’ endpoint cannot therefore be assessed in this case and are thus unsuitable for quantifying the extent of the additional benefit. The endpoint is presented for supplementary information only.
  • Thrombotic and cardiovascular events
  • No thrombotic or cardiovascular events occurred in any study arm during the RCP. The available data therefore show no relevant difference between the treatment arms.
  • Fatigue (FACIT-Fatigue)
  • The symptom scales of the EORTC QLQ-C30 are therefore not used for this assessment.
• quality of life
  • LASA
  • The responder analyses for deterioration show no statistically significant difference. In the responder analyses for improvement, statistically significant differences were observed between the treatment arms in favour of pegcetacoplan for all three individual scales of the LASA (activity level, ability to perform everyday activities and general quality of life). Given the uncertainties of the PEGASUS study outlined at the outset, the results cannot be evaluated and are therefore not suitable for quantifying the extent of the additional benefit.
  • EORTC QLQ-C30
  • The responder analyses for deterioration show no statistically significant difference. The responder analyses for improvement show statistically significant differences in the role functioning and physical function scales, as well as in the health status scale, in favour of pegcetacoplan. Given the uncertainties surrounding the PEGASUS study outlined above, the results cannot be evaluated and are therefore not suitable for quantifying the extent of the additional benefit.
• Side effects
  • Total adverse events (AEs)
  • AEs occurred in approximately 88% of patients in the intervention arm and approximately 85% of patients in the comparator arm. The results are presented here for supplementary information only.
  • Serious AEs (SAEs), severe AEs and therapy discontinuations due to AEs
  • There were no statistically significant differences between the treatment arms for the endpoints SAE, severe AEs and therapy discontinuations due to AEs.
  • AE of particular interest
  • In detail, with regard to AEs of particular interest, ‘injection site reaction’ and ‘reaction associated with an infusion’ showed statistically significant differences in favour of pegcetacoplan that are a disadvantage.
  • Overall, the results for the endpoint category ‘side effects’ cannot be assessed in light of the uncertainties of the PEGASUS study outlined at the outset and are therefore not suitable for quantifying the extent of the additional benefit.
• Overall assessment
  • Results from the PEGASUS study are available for the benefit assessment of pegcetacoplan for the treatment of adult patients with paroxysmal nocturnal haemoglobinuria (PNH) who remain anaemic after at least 3 months of treatment with a C5 inhibitor. During the 16-week, open-label, randomised controlled period (RCP) of the study, pegcetacoplan was compared with eculizumab.
  • PNH is a chronic condition. Against this background, the 16-week duration of the RCP in particular is considered too short overall to be able to quantify the extent of the additional benefit.
  • Furthermore, the study design is subject to significant uncertainties and limitations.
  • In summary, the available data on mortality, morbidity, quality of life and side effects do not allow for a quantification of the extent of the additional benefit of pegcetacoplan, particularly given the RCP’s duration of 16 weeks, which is too short.

Courtesy translation only, please refer to the German original.