Pegcetacoplan (4) – Aspaveli®

• Clinical trials
  • For the benefit assessment, the pharmaceutical manufacturer has submitted analyses of the Phase III VALIANT trial.
  • This was a multicentre, randomised, placebo-controlled, double-blind trial designed to investigate the safety and efficacy of pegcetacoplan in adult and adolescent patients aged 12 years and over with C3G or IC-MPGN.

Adults and adolescents aged 12 to 17 years with primary immune-complex-mediated membranoproliferative glomerulonephritis (IC-MPGN)

• Overall, there is a hint of a non-quantifiable additional benefit of pegcetacoplan for the treatment of adults and adolescents aged 12 to 17 years with IC-MPGN, as the scientific evidence does not permit quantification.
• mortality
  • No deaths occurred in the patient population under consideration.
• Morbidity – change in renal function, measured by proteinuria
  • The primary endpoint of the study was ‘change in renal function, measured by proteinuria’, operationalised, amongst other things, as the change in the log-transformed FMU-uPCR at week 26 compared with baseline.
  • This endpoint represents a laboratory parameter with no direct relation to symptoms.
  • For the present benefit assessment procedure, the pharmaceutical manufacturer has not submitted any suitable studies to validate proteinuria as a surrogate for a patient-relevant endpoint.
  • A conclusive assessment of any potential validation of proteinuria as a surrogate endpoint cannot therefore be carried out on the basis of the documents submitted in the present procedure.
  • The endpoint of proteinuria is therefore presented only as supplementary information.
  • There is a statistically significant difference in favour of pegcetacoplan compared with placebo.
• Morbidity – change in renal function, measured by eGFR
  • The endpoint ‘change in renal function, measured by eGFR’ was operationalised in the study as the change in eGFR at week 26 compared with baseline.
  • This endpoint represents a laboratory parameter with no direct relation to symptoms.
  • For the present benefit assessment procedure, the pharmaceutical manufacturer has not submitted any suitable studies to validate eGFR as a surrogate for a patient-relevant endpoint.
  • A final assessment of any potential validation of eGFR as a surrogate endpoint cannot therefore be carried out on the basis of the documents submitted in this procedure.
  • The eGFR endpoint is therefore presented only as supplementary information.
  • No statistically significant difference is observed between the treatment arms.
• Morbidity – Fatigue (FACIT-Fatigue, Peds FACIT-F)
  • The data on this endpoint cannot be assessed due to minor and, in some cases, highly variable response rates.
• Morbidity – WPAI:SHP (Question 6)
  • The data for this endpoint cannot be evaluated due to low response rates.
• Morbidity – EQ-5D VAS
  • The data for this endpoint cannot be assessed due to low response rates.
• Morbidity – PGI-C
  • Regardless of the suitability of the operationalisation, the response rates are too low and the data for these endpoints are therefore not evaluable.
• quality of life
  • The data for this endpoint cannot be assessed, as the proportion of participants included in the analysis at week 26 was 41.7% (pegcetacoplan arm) and 81.3% (placebo arm).
• Side effects – serious AEs (SAEs), severe AEs
  • For the endpoints SAE and severe AEs, there was no statistically significant difference between the treatment arms in either case.
• Side effects – Therapy discontinuation due to AEs
  • There were no therapy discontinuations due to AEs in either treatment arm.
• Overall assessment
  • Results from the randomised, double-blind VALIANT trial, in which pegcetacoplan was compared with placebo, are available for the benefit assessment of pegcetacoplan for the treatment of adults and adolescents aged 12 to 17 years with IC-MPGN.
  • No deaths occurred in the patient population under consideration.
  • With regard to the endpoint categories of morbidity and quality of life, the data cannot be assessed due to minor and, in some cases, highly variable response rates.
  • In the endpoint category of side effects, no overall advantages or disadvantages of pegcetacoplan compared with placebo can be inferred.

Courtesy translation only, please refer to the German original.