A Phase III study evaluating Merck & Co.’s prophylactic antiviral candidate letermovir met its primary and secondary endpoints of preventing the development of significant cytomegalovirus (CMV) infection in patients receiving an allogeneic hematopoietic stem cell transplant (HSCT). The firm says it plans to submit regulatory applications for letermovir in the EU and U.S. later this year.

The placebo-controlled Phase III study enrolled adult CMV-seropositive HSCT patients who had undetectable plasma CMV DNA. Letermovir therapy was started within the first 28 days following HSCT. The data showed that of the 495 patients who had undetectable CMV DNA at the start of the treatment, 37.5% of patients in the letermovir arm developed clinically significant CMV infection through to week 14, compared with 60.6% of patients in the placebo arm. The study also met its secondary endpoints, showing that significantly fewer patients in the letermovir arm (19.1%) developed clinically significant CMV infection through to week 14 post-HSCT, compared with placebo patients (50%). Letermovir was also associated with lower all-cause mortality.

“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 Francisco M. Marty, M.D., associate professor of medicine at Harvard Medical School, who presented the data at the recent combined annual meetings of the Center for International Blood & Marrow Transplant Research (CIBMTR) and the American Society for Blood and Marrow Transplantation (ASBMT), in Orlando. Dr. Marty is also attending physician in transplant and oncology infectious diseases at Dana-Farber Cancer Institute and Brigham and Women’s Hospital. “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,” he added.

Merck acquired global rights to develop and commercialize letermovir, and additional CMV candidates, from AiCuris, in 2012.

The Phase III letermovir results were reported just a couple of days after Merck announced positive data from its first Phase III study evaluating the inactivated varicella zoster virus vaccine (VZV) candidate V212. The study data, announced late Friday, showed that the vaccine reduced the incidence of herpes zoster (HZ, or shingles) by 64% in immunocompromised patients receiving auto-HSCT for any indication, including malignancy. The trial also found that V212 administration was associated with a 69.5% reduction in moderate-to-severe HZ pain and an estimated 83.7% reduction in the incidence of post-herpetic neuralgia (PHN) beyond 90 days after the onset of HZ. Treatment with V212 reduced other HZ complications by an estimated 73.5%. The Phase III trial data were also presented at the combined CIBMTR and ASBMT meeting.

Merck’s marketed HZ virus vaccine Zostavax® is contraindicated for use in immunocompromised patients.

“Patients undergoing auto-HSCT have an increased risk of HZ and associated complications due to impaired cellular immunity,” said Eliav Barr, M.D., senior vice president, Merck Research Laboratories. “These results indicate that V212 might offer a way to help reduce the risk of HZ and HZ-related complications in this vulnerable, immunocompromised patient population. We look forward to exploring these data further and to reviewing the results of an additional Phase III study that is underway in immunocompromised patients with malignancies.”

Less than 2 weeks ago Merck stopped a pivotal Phase II/III study with its Alzheimer’s disease candidate verubecestat after the external Data Monitoring Committee advised that the trial almost certainly wasn’t going to demonstrate any positive clinical benefits.



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