Results of the pivotal Phase 3 clinical study of letermovir, an investigational antiviral medicine for the prevention of clinically-significant cytomegalovirus (CMV) infection in adult CMV-seropositive recipients of an allogeneic hematopoietic stem cell transplant (HSCT) have been announced.

The results were presented for the first time at the BMT Tandem Meetings, the combined annual meetings of the Center for International Blood & Marrow Transplant Research (CIBMTR) and the American Society for Blood and Marrow Transplantation (ASBMT).

CMV is the most common clinically significant viral infection in allogeneic HSCT recipients.

While preemptive therapy (treatment when CMV DNA is detected in the blood) with antiviral medicines can reduce the incidence of CMV disease, CMV reactivation post-HSCT is associated with higher mortality despite the use of preemptive therapy.

Letermovir is an investigational once-daily antiviral medicine under development for the prevention of CMV infection and disease.

It is a member of a new class of non-nucleoside CMV inhibitors (3,4 dihydro-quinazolines) and inhibits viral replication by specifically targeting the viral terminase complex.

The study met its primary efficacy endpoint, showing that significantly fewer patients with undetectable CMV DNA at the start of study treatment developed clinically significant CMV infection (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].

Patients who discontinued the study early for any reason or who had missing data at Week 24 post-HSCT were considered study failures.

All adverse events were analysed through 14 days after the last dose of study drug.

In addition, a secondary endpoint evaluating the end-of-treatment period 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.

“These results showed that letermovir prophylaxis beginning after HSCT and continuing through Day 100 post-transplant significantly reduced CMV infection requiring preemptive antiviral therapy through Week 24 post-transplant,” said Dr. Francisco M. Marty, associate professor of medicine at Harvard Medical School and attending physician in transplant and oncology infectious diseases at Dana-Farber Cancer Institute and Brigham and Women’s Hospital, who presented the data. “In this study, letermovir was associated with lower all-cause mortality. Based on these findings, letermovir as primary prophylaxis of CMV infection represents a potential new strategy for the prevention of CMV in this high-risk patient population.”

Based on these results, Merck plans to submit regulatory applications for the approval of letermovir in the United States and European Union (EU) in 2017.

Source: Merck