Luspatercept (1) – Reblozyl®

• Clinical trials
  • For the benefit assessment of the active ingredient luspatercept, the pharmaceutical manufacturer submitted results from the ongoing pivotal Phase III trial BELIEVE (ACE-536-B-THAL-001).

Adult patients with transfusion-dependent anaemia associated with ꞵ-thalassaemia

• Hint for a non-quantifiable additional benefit, as the scientific data do not permit quantification.
• The strength of the evidence is classified as ‘hint’.
• mortality
  • Deaths are recorded as safety events in the BELIEVE study. At the time of the relevant data cut-off, one death occurred in each of the two treatment arms.
  • There is therefore no relevant difference in overall survival for the purposes of the benefit assessment.
• Morbidity – Hospitalisation
  • In the BELIEVE study, the endpoint ‘hospitalisation’ is defined as the number of patients hospitalised for any cause. There are statistically significant major differences in hospitalisations for any cause, at the disadvantage of luspatercept + BSC compared with placebo + BSC.
  • Overall, the endpoint category of morbidity shows a disadvantage for luspatercept + BSC compared with placebo + BSC in terms of hospitalisations.
• Morbidity – Transfusion-free period
  • A transfusion-free period of ≥ 24 weeks was observed in five patients in the intervention arm and in no patients in the control arm.
  • Based on the results regarding transfusion-free periods of ≥ 24 weeks, no statistically significant difference can be identified with regard to the long-term avoidance of transfusions (transfusion-free status).
• Quality of life – TranQoL
  • Overall, based on the difference in mean scores, no statistically significant difference was observed between the treatment arms.
• Quality of life – SF-36
  • There were no statistically significant differences between the treatment groups, either in terms of improvement or deterioration in the PCS or the MCS.
  • Overall, no statistically significant differences in health-related quality of life were observed between the treatment arms.
• Side effects – Serious adverse events (SAE), severe adverse events (CTCAE grade ≥ 3), therapy discontinuations due to adverse events
  • With regard to SAE, severe adverse events (CTCAE grade ≥ 3) and therapy discontinuations due to adverse events, there is a statistically significant disadvantage in each case compared with luspatercept + BSC compared with placebo + BSC.
  • An overall review of the results on side effects reveals that, compared with placebo + BSC, Luspatercept + BSC has a higher incidence of serious and severe adverse events (CTCAE grade ≥ 3) as well as therapy discontinuations due to adverse events, resulting in an overall significant disadvantage for Luspatercept + BSC compared with placebo + BSC in the side effects endpoint category.
• Side effects – bone pain (PT)
  • Among the other relevant safety events, there is a statistically significant disadvantage compared with luspatercept + BSC for bone pain (PT) compared with placebo + BSC.
• Overall assessment
  • Results from the BELIEVE study are available for the endpoint categories of mortality, morbidity, quality of life and side effects, for the assessment of the additional benefit of Luspatercept in the treatment of adult patients with transfusion-dependent anaemia associated with beta-thalassaemia.
  • In its overall assessment of the available results on patient-relevant endpoints, the G-BA classifies the extent of the additional benefit of luspatercept in the treatment of adult patients with transfusion-dependent anaemia, associated with beta-thalassaemia, as non-quantifiable on the basis of the criteria set out in Section 5(8), first sentence, 2 in conjunction with Section 5(7), first sentence, number 4 of the AM-NutzenV, as non-quantifiable, because the scientific evidence does not permit quantification.

Courtesy translation only, please refer to the German original.