Letermovir (2) – Prevymis®

• Clinical trials
  • The pharmaceutical manufacturer has submitted analyses of study MK-8228-002. This was a randomised, double-blind trial designed to investigate the efficacy and safety of letermovir compared with valganciclovir, which was conducted as a multicentre study at 94 centres in 16 countries.

CMV-seronegative adults who have received a kidney transplant from a CMV-seropositive donor, for the prophylaxis of CMV disease

• The additional benefit is not proven.
• mortality
  • For the endpoint of overall mortality, no statistically significant difference was observed between the study arms at the week 52 analysis point.
• Morbidity – Graft loss
  • For the endpoint of all-cause mortality, there was no statistically significant difference between the study arms at the 52-week analysis point.
• Morbidity – Severe CMV disease and total hospitalisation
  • The endpoint ‘severe CMV disease’ is defined as readmission to hospital due to CMV disease following initial discharge from hospital (re-hospitalisation).
  • At the 52-week analysis time point, there was no statistically significant difference between the treatment arms.
  • The overall hospitalisation rate also did not differ statistically significantly at the same analysis time point.
• Morbidity – CMV end-organ disease
  • The endpoint ‘CMV end-organ disease’ was operationalised as clinical manifestation in at least one organ system in addition to evidence of CMV.
  • No statistically significant difference was observed between the treatment arms.
• Morbidity – New-onset diabetes mellitus after transplantation (NODAT)
  • For the NODAT endpoint, defined as the first occurrence of (manifest) diabetes mellitus following kidney transplantation in accordance with the criteria of the WHO and the American Diabetes Association, no statistically significant difference was observed between the treatment groups.
• Morbidity – Health status (EQ-5D-VAS)
  • Analysis of participants showing an improvement of at least 15% (15 points on a 100-point scale) revealed no statistically significant difference between the treatment groups.
• Quality of life – SF-36v2
  • There was no statistically significant difference between the treatment arms in any of the total scores.
• Side effects
  • The proportion of patients experiencing severe adverse events was comparable between the treatment arms.
  • For the endpoint of therapy discontinuation due to adverse events, there was a statistically significant difference in favour of letermovir.
  • For the events that led to therapy discontinuation, there is insufficient information on the severity category to allow them to be classified as serious or severe. The endpoint ‘discontinuation due to adverse events’ is therefore classified under the endpoint category ‘non-serious / non-severe side effects’.
  • The statistically significant advantage in the endpoint ‘therapy discontinuation due to adverse events’ is observed only in males.
  • When examining specific adverse events in detail, a statistically significant disadvantage for letermovir is evident for the endpoint ‘general disorders and administration site conditions’.
• Overall assessment
  • In the endpoint categories of mortality, morbidity and health-related quality of life, there are neither advantages nor disadvantages for letermovir.
  • In the endpoint category ‘side effects’, an advantage for letermovir over valganciclovir is evident exclusively in the endpoint ‘therapy discontinuation due to adverse events’.
  • However, for this endpoint, there is an effect modification for the characteristic of sex. The advantage is evident only in the subpopulation of men, but not in the subpopulation of women.
  • Furthermore, due to the low response rates in both treatment arms, there is a high degree of uncertainty in the assessment of the endpoints health status (EQ-5D-VAS) and health-related quality of life (SF-36v2).
  • On balance, the advantage—which is observed exclusively at the endpoint of therapy discontinuation due to adverse events—is not considered sufficient to demonstrate additional benefit.

Courtesy translation only, please refer to the German original.