Letermovir (4) – Prevymis®

• Clinical trials
  • The pharmaceutical manufacturer presents the results of study MK-8228-030 (P030). This is an open-label, single-arm Phase 2b trial to evaluate the pharmacokinetics, efficacy, safety and tolerability of letermovir in the prophylaxis of cytomegalovirusinfections in children and adolescents aged 0 to < 18 years who are at risk of developing a clinically significant cytomegalovirus infection following an allogeneic haematopoietic stem cell transplant.

CMV-seropositive recipients [R+] aged 0 to < 18 years with a body weight of at least 5 kg following allogeneic haematopoietic stem cell transplantation, for whom prophylaxis against cytomegalovirus (CMV) reactivation and disease is indicated

• Hint for a non-quantifiable additional benefit.
• Taking into account the identified uncertainties regarding study P001, as well as the uncertainty arising from extrapolating the additional benefit to a younger patient population, only a hint of certainty can be established.
• Morbidity – clinically significant CMV infection at week 24
  • In study P030, the proportion of participants with a clinically significant cytomegalovirus infection – defined as the occurrence of cytomegalovirus end-organ damage or the initiation of pre-emptive anti-cytomegalovirustherapy due to documented cytomegalovirus viremia, was 10.7% at week 24 post-transplantation, which was lower than the proportion observed in the overall population of study P001 (17.5%).
  • The results were comparable across all three age groups (12 to under 18 years, 2 to under 12 years and under 2 years). No cases of cytomegalovirus end-organ damage were observed.
  • The initiation of pre-emptive therapy is prompted by CMV viraemia in both clinical practice and the study, although the treating clinician’s individual assessment of the patient’s clinical symptoms also influences the decision.
  • In view of the fact that a sufficiently comparable treatment situation exists, and taking into account the EMA’s findings regarding the medical rationale for extrapolating the data and the observed consistent effects on the morbidity endpoint ‘clinically significant CMV infection at week 24’”, it is assumed that the positive effects of letermovir are transferable from the adult population to the population of children and adolescents (< 18 years), and a non-quantifiable additional benefit is inferred.
• Side effects
  • Secondary endpoints included clinically significant CMV infections in the morbidity category, as well as endpoints in the side effect category.
• Overall assessment
  • Particularly in view of the fact that a sufficiently comparable treatment situation exists, and taking into account the EMA’s findings regarding the medical rationale for the transfer of data and the observed consistent effects in the morbidity endpoint ‘clinically significant CMV infection at week 24’, it is assumed that the positive effects of letermovir are transferable from the adult population to the population of children and adolescents (< 18 years), and a non-quantifiable additional benefit is inferred.

Courtesy translation only, please refer to the German original.