Colestilan (1) – BindRen®

• Clinical trials
  • To assess the additional benefit compared with the appropriate comparator therapy ‘calcium acetate’, two randomised, comparative, open-label marketing authorisation trials (MCI-196-A01 and MCI-196-A03) with their respective extension studies (MCI-196-A02 and MCI-196-A04).
  • To assess the additional benefit compared with the appropriate comparator therapy, a randomised, comparative, open-label registration study (MCI-196-E07) with its extension study (MCI-196-E10) is available.

Hyperphosphataemia in adults with stage 5 chronic kidney disease (CKD) undergoing haemodialysis or peritoneal dialysis

• The additional benefit of Colestilan for the treatment of hyperphosphataemia in adults with stage 5 chronic kidney disease (CKD) undergoing haemodialysis or peritoneal dialysis is not proven.
• mortality
  • The endpoint ‘overall survival’ was recorded in study MCI-196-E07 as ‘deaths during the study period’.
  • In terms of study duration and patient numbers, the study was not designed to demonstrate differences in overall survival.
  • Due to the low proportion of patients experiencing an event and the short study duration, the endpoint ‘overall survival’ is not suitable for assessing additional benefit.
• Morbidity – Cardiovascular events (heart disease, vascular disease)
  • The endpoint ‘cardiovascular events’ was recorded in study MCI-196-E07 as the overall rate of occurrence of cardiovascular events (safety population).
  • There were no statistically significant differences between the Colestilan arm and the sevelamer arm.
  • Therefore, no greater benefit of Colestilan over sevelamer can be inferred for the endpoint ‘cardiovascular events’.
• Morbidity – disorders of the nervous system
  • The endpoint ‘disorders of the nervous system’ was recorded in study MCI-196-E07 as the overall incidence rate of nervous system disorders (safety population).
  • Due to the minor number of patients who experienced an event, no statistically significant differences can be identified between the Colestilan arm and the sevelamer arm.
  • Consequently, no conclusions regarding additional benefit can be drawn for the endpoint ‘neurological disorders’.
• Morbidity – Symptomatic fractures (vertebral fractures, non-vertebral fractures)
  • The endpoint ‘symptomatic fractures’ was recorded in study MCI-196-E07 as the overall rate of symptomatic vertebral and non-vertebral fractures (safety population).
  • Due to the minor number of patients in whom an event occurred, no statistically significant differences could be identified between the Colestilan arm and the sevelamer arm.
  • No conclusions can therefore be drawn regarding greater benefit or harm of Colestilan compared with sevelamer for the endpoint ‘symptomatic fractures’.
• Morbidity – Hypercalcaemia (symptomatic hypercalcaemia, hypercalcaemic crisis)
  • The endpoint ‘symptomatic hypercalcaemia’ was recorded in study MCI-196-E07 as the overall rate of occurrence of symptomatic hypercalcaemia.
  • No hypercalcaemic crisis occurred in either study arm.
  • Due to the minor number of patients who experienced a hypercalcaemic event, no statistically significant differences can be identified between the Colestilan arm and the sevelamer arm.
  • No conclusions regarding additional benefit can therefore be drawn for the endpoint ‘symptomatic hypercalcaemia’.
• quality of life
  • Data on quality of life were not collected in the study.
  • The endpoint ‘quality of life’ is therefore not usable for assessing the additional benefit of Colestilan.
• Side effects
  • There were statistically significantly more therapy discontinuations due to adverse events in the Colestilan arm compared with the sevelamer arm.
  • A downgrading of the additional benefit to less benefit compared with the appropriate comparator therapy, on the basis of the higher rate of therapy discontinuations in the Colestilan arm, does not appear justified, not least because of uncertainties arising from the study design.
• Overall assessment
  • Taking into account the available results on mortality, morbidity and quality of life, as well as the findings on side effects, Colestilan offers no additional benefit compared with the appropriate comparator therapy, ‘sevelamer’.

Courtesy translation only, please refer to the German original.