Vutrisiran (2) – Amvuttra®

• Clinical trials
  • This trial is a double-blind RCT comparing vutrisiran with placebo.
  • This assessment is based on the HELIOS-B trial, which formed the basis for marketing authorisation.

Adults with wild-type or hereditary transthyretin amyloidosis with cardiomyopathy (ATTR-CM)

• For adults with wild-type or hereditary transthyretin amyloidosis with cardiomyopathy (ATTR-CM), the additional benefit is not proven.
• For vutrisiran in the treatment of adults with wild-type or hereditary transthyretin amyloidosis with cardiomyopathy, therefore, an additional benefit is not proven compared with the appropriate comparator therapy, tafamidis.
• mortality
  • The pharmaceutical manufacturer provides supplementary data in the benefit assessment dossier on the outcome categories of mortality, morbidity, health-related quality of life and side effects, both for the overall population and for the patient population not receiving background treatment with tafamidis.
  • The primary endpoint of the study is a composite endpoint comprising all-cause mortality and recurrent cardiovascular events.
• morbidity
  • The pharmaceutical manufacturer shall additionally present results in the benefit assessment dossier for the endpoint categories of mortality, morbidity, health-related quality of life and side effects, both for the overall population and for the patient population without prior treatment with tafamidis.
  • The primary endpoint of the study is a composite endpoint comprising all-cause mortality and recurrent cardiovascular events.
• Health-related quality of life
  • The pharmaceutical manufacturer shall additionally present results in the benefit assessment dossier for the endpoint categories of mortality, morbidity, health-related quality of life and side effects, both for the overall population and for the patient population without prior treatment with tafamidis.
• Side effects
  • The pharmaceutical manufacturer shall additionally present results in the benefit assessment dossier for the endpoint categories of mortality, morbidity, health-related quality of life and side effects, both for the overall population and for the patient population without prior treatment with tafamidis.
• Overall assessment
  • However, a significant proportion of the included patients (a total of 40% of study participants) were already receiving background therapy with Tafamidis at the time of randomisation, which was continued throughout the remainder of the study.
  • The study would therefore allow for comparative assessments of vutrisiran in combination with tafamidis versus tafamidis as monotherapy for a patient population of the included study participants.
  • However, despite being requested to do so, the pharmaceutical manufacturer has not provided the data for this patient population in a separate format.
  • This approach by the pharmaceutical manufacturer is viewed critically.

Courtesy translation only, please refer to the German original.