Tenofoviralafenamid (1) – Vemlidy®

• Clinical trials
  • To demonstrate the additional benefit, the pharmaceutical manufacturer has submitted interim results from the randomised, double-blind and multicentre clinical trials GS108 and GS110.
  • These studies are regulatory trials comparing tenofovir alafenamide with tenofovir disoproxil in adult patients with chronic hepatitis B infection who are HBe-positive (GS0110) or HBe-negative (GS0108) HBe antigen status.

a) treatment-naïve adult patients with chronic hepatitis B

• No additional benefit of tenofovir alafenamide over the appropriate comparator therapy has been proven in any patient group.
• Taken together, the approach described does not satisfy the requirements for demonstrating the additional benefit of its medicinal product over the appropriate comparator therapy, as set out in Section 35a(1) of the German Social Code, Book V (SGB V), which are incumbent upon the pharmaceutical manufacturer.
• To this end, all data relevant to the assessment of additional benefit must be presented in the dossier in a complete and substantively comprehensible manner.
• Applying the legally prescribed standard, it is not possible, on the basis of the evidence submitted by the pharmaceutical manufacturer, to conclusively assess to what extent the results presented provide a complete picture of the benefit of the medicinal product under assessment.
• The presentation of the results is therefore found to be inadequate for the benefit assessment, meaning that it is not possible to assess the additional benefit or any potential harm.
• In Module 4 of the dossier, apart from the overall rates of adverse events, only those categories of adverse events deemed relevant by the pharmaceutical manufacturer and of particular interest – namely ‘kidney disorders’ and ‘changes in bone density/fractures’; there is no listing of further specific or frequent adverse events, nor a complete breakdown of the adverse events by System Organ Class (SOC) and Preferred Term (PT), which would enable the pharmaceutical manufacturer’s selection to be verified.
• In particular, the approach described renders the process of selecting the aforementioned adverse events of particular interest non-transparent, which is why its content cannot be verified and its appropriateness cannot be assessed.
• The selective presentation of the adverse effects of particular interest selected by the pharmaceutical manufacturer – ‘renal disorders’ and ‘changes in bone density / fractures’ – without a complete presentation of all adverse events according to SOC and PT – is of particular significance for the benefit assessment of tenofovir alafenamide, as the pharmaceutical manufacturer bases its justification of the additional benefit compared with the appropriate comparator therapy predominantly on these two endpoints.

b) treatment-experienced adult patients with chronic hepatitis B

• No additional benefit of tenofovir alafenamide over the appropriate comparator therapy has been proven in any patient group.
• Taken together, the approach described does not satisfy the requirements for demonstrating additional benefit of the medicinal product over the appropriate comparator therapy, as set out in Section 35a(1) of the German Social Code, Book V (SGB V), which are incumbent upon the pharmaceutical manufacturer.
• To this end, all data relevant to the assessment of additional benefit must be presented in the dossier in a complete and substantively comprehensible manner.
• Applying the legally prescribed standard, it is not possible, on the basis of the evidence submitted by the pharmaceutical manufacturer, to conclusively assess to what extent the results presented provide a complete picture of the benefit of the medicinal product under assessment.
• The presentation of the results is therefore found to be inadequate for the benefit assessment, meaning that it is not possible to assess the additional benefit or any potential harm.
• In Module 4 of the dossier, apart from the overall rates of adverse events, only those categories of adverse events deemed relevant by the pharmaceutical manufacturer and of particular interest – namely ‘kidney disorders’ and ‘changes in bone density/fractures’; there is no listing of further specific or frequent adverse events, nor a complete breakdown of the adverse events by System Organ Class (SOC) and Preferred Term (PT), which would enable the pharmaceutical manufacturer’s selection to be verified.
• In particular, the approach described renders the process of selecting the aforementioned adverse events of particular interest non-transparent, which is why its content cannot be verified and its appropriateness cannot be assessed.
• The selective presentation of the adverse effects of particular interest selected by the pharmaceutical manufacturer – ‘renal disorders’ and ‘changes in bone density / fractures’ – without a complete presentation of all adverse events according to SOC and PT – is of particular significance for the benefit assessment of tenofovir alafenamide, as the pharmaceutical manufacturer bases its justification of the additional benefit compared with the appropriate comparator therapy predominantly on these two endpoints.

c) treatment-naïve adolescent patients aged 12 years and over with chronic hepatitis B

• No additional benefit of tenofovir alafenamide over the appropriate comparator therapy has been proven in any patient group.
• No results from clinical trials were submitted for the benefit assessment for patient populations c) and d).
• The pharmaceutical manufacturer’s search failed to identify any relevant studies, meaning that no comparison with the appropriate comparator therapy is possible.
• No conclusions regarding additional benefit can be drawn.

d) treatment-experienced adolescent patients aged 12 years and over with chronic hepatitis B

• No additional benefit of tenofovir alafenamide compared with the appropriate comparator therapy has been proven in any patient group.
• No results from clinical trials were submitted for the benefit assessment for patient populations c) and d).
• The pharmaceutical manufacturer’s search failed to identify any relevant studies, meaning that no comparison with the appropriate comparator therapy is possible.
• No conclusions regarding additional benefit can be drawn.

Courtesy translation only, please refer to the German original.