Sutimlimab (1) – Enjaymo®

• Clinical trials
  • The CADENZA trial is a multicentre, randomised, double-blind, placebo-controlled trial.
  • The CARDINAL study is a multicentre, single-arm study.

Adults with haemolytic anaemia associated with cold agglutinin disease

• Hint of a minor additional benefit.
• Taking the available results as a whole, the advantage observed for the endpoint ‘fatigue’ is not offset by any disadvantage. Consequently, the G-BA classifies the extent of the additional benefit of sutimlimab for the treatment of haemolytic anaemia in adults with cold agglutinin disease (CAD) as minor.
• The strength of the evidence is classified as ‘hint’.
• mortality
  • Overall survival was not assessed as an independent endpoint in the CADENZA study. Deaths were recorded as part of the adverse event monitoring. In Part A, no deaths occurred in any of the study arms. The available data therefore show no major difference between the treatment arms.
• Morbidity – Health status
  • In the CADENZA study, patients’ self-reported health status was assessed using the visual analogue scale of the EQ-5D-5L.
  • There was no statistically significant difference between the treatment arms.
• Morbidity – Fatigue
  • Data on fatigue were collected in the CADENZA study using the FACIT-Fatigue questionnaire.
  • A statistically significant advantage in favour of sutimlimab was observed in the mean change from baseline to the treatment assessment time (TAT; weeks 23, 25 and 26). The proportion of missing values at TAT was 14% in the sutimlimab arm and 0% in the comparator arm. Based on the standardised mean difference (Hedges’ g), a clinically relevant difference is assumed.
• Morbidity – Thromboembolic events
  • In the CADENZA trial, one thromboembolic event occurred in the intervention arm; none occurred in the control arm. The available data therefore show no relevant difference between the treatment arms.
• quality of life
  • Data on health-related quality of life were collected in the CADENZA study using the Short-Form 12 Health Survey (SF-12).
  • No statistically significant difference was observed between the treatment arms for either the mental health summary score (MCS) or the physical health summary score (PCS).
• Side effects – Total adverse events (AEs)
  • Almost all patients in both the intervention and control arms experienced an adverse event. The results are presented here for supplementary information only.
• Side effects – serious AEs (SAEs), severe AEs (CTCAE grade ≥ 3) and therapy discontinuations due to AEs
  • No statistically significant differences were observed between the treatment arms for the endpoints SAE, severe AEs (CTCAE grade ≥ 3) and therapy discontinuations due to AEs.
• Side effects – AEs of particular interest
  • In detail, there were also no statistically significant or relevant differences between the treatment arms for the AEs of particular interest for which the pharmaceutical manufacturer provided p-values.
  • When interpreting the results on side effects, it should be noted that, for the CADENZA study, the pharmaceutical manufacturer provided p-values for the side effect endpoints only for the overall rates and for a subset of AEs of particular interest. Effect estimates and associated confidence intervals were not reported by the pharmaceutical manufacturer.
• Overall assessment
  • Results from the CADENZA and CARDINAL studies are available for the benefit assessment of sutimlimab for the treatment of haemolytic anaemia in adults with cold agglutinin disease (CAD). This assessment is based on the randomised, controlled Part A of the CADENZA study, in which sutimlimab was compared with placebo.
  • With regard to overall survival, no deaths occurred in either study arm. The available data therefore show no relevant difference.
  • In the morbidity endpoint category, results are available on health status, fatigue and thromboembolic events. For the fatigue endpoint, a statistically significant and clinically relevant advantage was observed in favour of sutimlimab. Given that fatigue is one of the main symptoms of cold agglutinin disease, this effect is considered a significant advantage for patients.
  • With regard to health-related quality of life, the SF-12 results show no statistically significant differences between the treatment arms.
  • Similarly, there were no differences between sutimlimab and placebo in terms of side effects that were relevant to the assessment.

Courtesy translation only, please refer to the German original.