DNA thresholds for the initiation of PET during the treatment period was ≥ 150 copies/mL or > 300 copies/mL for subjects in the high and low risk strata, respectively. From Week 14 through Week 24, the threshold was >300 copies/mL for both high and low risk strata subjects. The Non-Completer=Failure (NC=F) approach was used, where subjects who discontinued from the trial prior to Week 24 post-transplant or had a missing outcome at Week 24 post-transplant were counted as failures.Efficacy results from Trial P001 are shown in Table 7.Table 7: Trial P001 Efficacy Results in HSCT Recipients (NC=F Approach, FAS Population) Through Week 24ParameterLetermovir(N=325)Placebo(N=170)Note: FAS=Full analysis set; FAS includes randomized subjects who received at least one dose of study medication, and excludes subjects with detectable CMV DNA at baseline. Approach to handling missing values: Non-Completer=Failure (NC=F) approach. With NC=F approach, failure was defined as all subjects who developed clinically significant CMV infection or prematurely discontinued from the study or had a missing outcome through Week 24 post-transplant visit window.Proportion of subjects who failed prophylaxis38%61%Reasons for failuresThe categories of failure are mutually exclusive and based on the hierarchy of categories in the order listed. Clinically significant CMV infection by Week 24Through Week 14, 8% of subjects in the PREVYMIS group and 39% of subjects in the placebo group experienced clinically significant CMV infection.18%42% Initiation of PET based on documented CMV viremia16%40% CMV end-organ disease2%2% Discontinued from study before Week 24Reasons for discontinuation included adverse event, death, lost to follow-up, physician decision, and withdrawal by subject.17%16% Missing outcome in Week 24 visit window3%3%Stratum-adjusted treatment difference (Letermovir-Placebo)95% CI and p-value for the treatment differences in percent response were calculated using stratum-adjusted Mantel-Haenszel method with the difference weighted by the harmonic mean of sample size per arm for each stratum (high or low risk). Difference (95% CI)-23.5 (-32.5, -14.6)p-value <0.0001.Efficacy results were consistent across high and low risk strata for CMV reactivation. The time to clinically significant CMV infection is shown in Figure 1.Figure 1: P001: Kaplan-Meier Plot of Time to Onset of Clinically Significant CMV Infection Through Week 24 Post-Transplant in HSCT Recipients (FAS Population)Post-hoc analysis demonstrated that among PREVYMIS-treated subjects, inclusion in the high risk stratum for CMV reactivation at baseline, occurrence of GVHD, and steroid use at any time after randomization may be associated with the development of clinically significant CMV infection between Week 14 and Week 24 post-transplant.
MortalityThe Kaplan-Meier event rate for all-cause mortality in the letermovir vs. placebo groups was 12% vs. 17% at Week 24 post-transplant, and 24% vs. 28% at Week 48 post-transplant.
Tablets:Each PREVYMIS 240 mg tablet is a yellow oval tablet; each tablet is debossed with "591" on one side and Merck logo on the other side. Each PREVYMIS 480 mg tablet is a pink oval, bi-convex tablet debossed with "595" on one side and Merck logo on the other side.The 240 mg tablets are packaged into a carton (NDC 0006-3075-02) containing four (4) Child Resistant (CR) Dosepaks® |
