Iptacopan (4) – Fabhalta®

Adults with complement-3 glomerulopathy (C3G)

• For adults with complement-3 glomerulopathy, the additional benefit is not proven.
• Taking the results as a whole, the data presented are, on the whole, insufficient to justify the conclusion that there is additional benefit compared with the appropriate comparator therapy.
• mortality
  • No deaths occurred in the relevant patient population.
• Morbidity – Fatigue (FACIT-Fatigue, PGI-S)
  • The endpoint of fatigue is fundamentally relevant to the assessment.
  • However, the analyses of the patient-reported endpoints from the APPEAR-C3G study are not suitable, as baseline values are available for only 6 of the 9 patients in the comparator arm.
  • This represents too great a difference between the treatment groups (> 15 percentage points) in terms of the proportion of patients who were not included in the analysis.
• Morbidity – Health status (EQ-5D-VAS)
  • The health status endpoint is generally relevant for the assessment.
  • However, the analyses of the patient-reported endpoints from the APPEAR-C3G study are not suitable (see comments on the fatigue endpoint).
• Morbidity – Proteinuria (UPCR)
  • The pharmaceutical manufacturer presents several operationalisations for the endpoint ‘proteinuria’ (UPCR, based on a 24-hour urine collection), including the change in UPCR from baseline.
  • The endpoint represents a laboratory parameter with no direct relation to symptoms.
  • The pharmaceutical manufacturer has not provided any surrogate validation in the dossier.
  • On the basis of the available information, it is therefore not possible to evaluate proteinuria as a surrogate endpoint.
  • The endpoint of proteinuria is therefore presented only as supplementary information.
• Morbidity – Glomerular filtration rate (eGFR)
  • The pharmaceutical manufacturer has specified operationalisations of ≤ 10 % and ≤ 15 % reduction from baseline for the glomerular filtration rate (eGFR) endpoint.
  • The endpoint is a laboratory parameter with no direct relation to symptoms.
  • The pharmaceutical manufacturer has not provided any surrogate validation in the dossier.
  • The endpoint is therefore not used for the benefit assessment.
• Quality of life – SF-36
  • The physical composite score (PCS) and mental composite score (MCS) of the Short Form-36 Health Survey (SF-36) are, in principle, relevant for the assessment.
  • However, in its dossier on this patient-reported endpoint, the pharmaceutical manufacturer has submitted analyses that are not suitable (see comments on the fatigue endpoint).
• Side effects – Serious adverse events (SAE)
  • For the SAE endpoint, there is no statistically significant difference between the treatment arms.
• Side effects – Discontinuation due to adverse events (AE)
  • No ‘discontinuation due to AEs’ occurred in the relevant patient population.
• Side effects – Specific AEs (infections)
  • In detail, for the specific AE ‘infections’ – defined as infections and parasitic diseases (SOC, AEs and SEs) – there was no statistically significant difference between the treatment arms with regard to ‘infections (AE)’ was found, whilst no events occurred in the relevant patient population with regard to ‘infections (SAE)’.
• Overall assessment
  • No deaths occurred in the relevant patient population of the study.
  • In the morbidity category, no suitable data are available for the endpoints fatigue (FACIT-Fatigue, PGI-S) and health status (EQ-5D-VAS).
  • In the health-related quality of life category, there are also no suitable data available for the SF-36 endpoint (physical summary score and mental summary score).
  • In the side effects category, there was no statistically significant difference between the treatment arms in the overall rates of serious side effects (SAEs).
  • Furthermore, there were no therapy discontinuations due to AEs in the relevant patient population.
  • Taking the results as a whole, the data presented are, on the whole, insufficient to justify the conclusion that there is an additional benefit compared with the appropriate comparator therapy.

Courtesy translation only, please refer to the German original.