Cytomegalovirus (CMV) Retinitis

December 11, 2017

Merck & Co. released pivotal phase III study results of PREVYMIS (letermovir) for prophylaxis (prevention) of cytomegalovirus (CMV) infection and disease in adult CMV-seropositive recipients [R+] of an allogeneic hematopoietic stem cell transplant (HSCT). In the study, significantly fewer patients in the PREVYMIS arm (37.5%, n=122/325) compared to the placebo arm (60.6%, n=103/170) developed clinically significant CMV infection, discontinued treatment or had missing data through Week 24 post-transplant (p<0.001), the primary efficacy endpoint. The treatment effect for PREVYMIS in preventing clinically significant CMV infection was consistent across pre-specified high- and low-risk strata for CMV reactivation both at week 14 (end of treatment) and at week 24 post-transplant. All-cause mortality in patients receiving PREVYMIS was lower compared to placebo at Week 24 post-transplant and at week 48 post-transplant. This double-blind study randomized adult CMV-seropositive allogeneic hematopoietic-cell transplant recipients to receive PREVYMIS or placebo orally or intravenously through week 14 post-transplant. PREVYMIS was dosed at 480mg/day (or 240mg/day when co-administered with cyclosporine).  

March 6, 2017

Merck & Co. issued results of a phase III study of letermovir for the prevention of clinically significant cytomegalovirus (CMV) infection in adult (18 years and older) CMV-seropositive recipients of an allogeneic hematopoietic stem cell transplant (HSCT), also known as bone marrow transplant (BMT). CMV seropositive HSCT recipients who had undetectable plasma CMV DNA within five days of randomization were eligible for the study. Patients were randomized in a 2:1 ratio to receive either letermovir or placebo administered once daily, either in oral tablet or intravenous formulation, through week 14 (day 100) post-HSCT. Letermovir was dosed at 480mg/day (or 240mg/day if the patient was on the immunosuppressant medication cyclosporine). Letermovir was started after HSCT, as early as the day of transplant and no later than 28 days post-transplant. The study met its primary efficacy endpoint, showing that of 495 treated patients who had undetectable CMV DNA at the start of study treatment, significantly fewer patients developed clinically significant CMV infection in the letermovir arm (37.5%, n=122/325) compared to the placebo arm (60.6%, n=103/170) through week 24 post-HSCT [treatment difference: -23.5 (95% confidence interval -32.5 to -14.6), one-sided p<0.0001]. In addition, a secondary endpoint evaluating the end-of-treatment period (at week 14 post-HSCT) showed that significantly fewer patients developed clinically significant CMV infection in the letermovir arm (19.1%, n=62/325) compared to the placebo arm (50.0%, n=85/170) through week 14 (day 100) post-HSCT [treatment difference: -31.3 (95% confidence interval -39.9 to -22.6), one-sided p<0.0001]. In this study, letermovir was associated with lower all-cause mortality through week 24 post-HSCT (9.8%, n=32/325) compared to placebo (15.9%, n=27/170), log-rank two-sided p=0.0317. The company will submit regulatory applications for letermovir in 2017. 

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