Pegcetacoplan (3) – Aspaveli®

• Clinical trials
  • For the benefit assessment, the pharmaceutical manufacturer has submitted analyses of the Phase III VALIANT trial.

Adults and adolescents aged 12 to 17 years with complement-3 glomerulopathy (C3G)

• Overall, there is a hint of a non-quantifiable additional benefit of pegcetacoplan for the treatment of adults and adolescents aged 12 to 17 with C3G, as the scientific evidence does not permit quantification.
• In summary, the additional benefit of pegcetacoplan is assessed as follows: a hint of a non-quantifiable additional benefit, as the scientific evidence does not permit quantification.
• mortality
  • Deaths were recorded as part of the safety monitoring. In total, one death occurred in the active treatment arm within the patient population under consideration. There was no statistically significant difference between the treatment arms.
  • In the patient population under consideration, one death occurred among patients treated with pegcetacoplan. Overall, there was no statistically significant difference between the treatment arms for the endpoint of all-cause mortality.
• 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. Within the G-BA, there are differing views as to whether proteinuria constitutes a patient-relevant endpoint in its own right. Proteinuria – together with eGFR – represents a relevant parameter for guiding treatment in the present therapeutic indication.
  • 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 the potential validation of proteinuria as a surrogate endpoint cannot therefore be made on the basis of the documentation submitted in this procedure. The endpoint ‘proteinuria’ is therefore presented only as supplementary information. A statistically significant difference in favour of pegcetacoplan compared with placebo is observed.
  • Among the endpoints presented as supplementary, a statistically significant difference in favour of pegcetacoplan is observed for the ‘proteinuria’ endpoint.
• Morbidity – Change in renal function, measured by the estimated glomerular filtration rate (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. Within the G-BA, there are differing views as to whether renal function, as measured by eGFR, constitutes a patient-relevant endpoint in its own right. The eGFR – together with proteinuria – represents a relevant parameter for guiding treatment in the present therapeutic indication.
  • 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 conclusive assessment of the potential validation of eGFR as a surrogate endpoint cannot therefore be made on the basis of the documentation submitted in this procedure. The eGFR endpoint is therefore presented only as supplementary information. No statistically significant difference was observed between the treatment arms.
• Morbidity – Fatigue (FACIT-Fatigue, Peds FACIT-F)
  • The ‘fatigue’ endpoint was assessed in the study using FACIT-Fatigue for adults and Peds FACIT-F for children and adolescents aged between 12 and 17 years.
  • The data for this endpoint cannot be evaluated due to minor and, in some cases, highly variable response rates.
• Morbidity – WPAI:SHP (Question 6)
  • The ‘Work Productivity and Activity Impairment Questionnaire: Specific Health Problem’ (WPAI:SHP) serves as a tool for disease-specific assessment of self-reported impairments in working life among adults and also includes a question on impairment of other daily activities.
  • The data for this endpoint cannot be assessed due to minor response rates.
• Morbidity – EQ-5D VAS
  • Self-assessed general health status was assessed in the study using the ‘European Quality of Life 5-Dimension 5-Level’ (EQ-5D-5L). The visual analogue scale used in the EQ-5D-5L (EQ-5D VAS) measures current health status on a scale from 100 (‘best possible health’) to 0 (‘worst possible health’).
  • The data for this endpoint cannot be evaluated due to minor response rates.
• Morbidity – PGI-C
  • The current version of the ‘Patient Global Impression of Change’ (PGIC) is intended to assess, in this study, the patient-reported change in general health status since the start of treatment.
  • Regardless of the suitability of the operationalisation, the response rates are too minor and the data for these endpoints are therefore not evaluable.
• Quality of life – KDQOL-36
  • In the quality of life endpoint category, no statistically significant difference between the treatment arms was observed in any domain for the KDQOL-36 endpoint.
• Side effects – serious adverse events
  • With regard to side effects, there are no differences relevant to the benefit assessment in terms of severe adverse events or therapy discontinuations due to adverse events.
• Overall assessment
  • With regard to the morbidity endpoint category, the data cannot be assessed due to minor and, in some cases, highly variable response rates.
  • In the quality of life endpoint category, no statistically significant difference was observed between the treatment arms in any domain of the KDQOL-36 endpoint.
  • In the ‘side effects’ endpoint category, no overall advantages or disadvantages of pegcetacoplan compared with placebo can be identified.

Courtesy translation only, please refer to the German original.