Merck's First-in-Class Cytomegalovirus Inhibitor Letermovir Approved in China for Prevention of CMV Reactivation in Allogeneic HSCT Recipients

Source: PharmaCube Info

Author: PharmaCube Info

On January 5, MSD's Letermovir Tablets received approval from the National Medical Products Administration (NMPA) for marketing in China. It is indicated for adult recipients [R+] of allogeneic hematopoietic stem cell transplantation (HSCT) who are cytomegalovirus (CMV) seropositive, to prevent CMV reactivation and disease. Letermovir is the world’s first and only approved inhibitor of the cytomegalovirus (CMV) DNA terminase complex.

CMV is a common type of herpesvirus, with a seropositivity rate in human serum ranging from 30% to 97%. In individuals with normal immune function, CMV infection typically presents as short-term fever or is asymptomatic. Afterward, CMV remains latent for life in various cells, serving as a reservoir for reactivation, and carriers become susceptible populations. When the immune system is functioning well, most CMV infections are latent. However, transplant patients, who are in an immunosuppressed state, have a much higher incidence of secondary CMV infection post-surgery compared to the general population. CMV pneumonia is not only a common infectious complication in transplant recipients but also one of the significant causes of mortality.

Allogeneic hematopoietic stem cell transplantation (Allo-HSCT) has been successfully used for the treatment of hematological diseases, but post-transplant infections remain a significant factor affecting survival. Among these, CMV infection is the most common viral infection after transplantation, mostly occurring within 100 days post-transplant. If not treated promptly, it can lead to multi-organ dysfunction and even endanger life.

Letermovir inhibits the CMV virus DNA terminase complex (pUL51, pUL56, pUL89). This enzyme is responsible for the processing and packaging of viral DNA. Biochemical characteristics and electron microscopy observations indicate that letermovir affects the production of unit-length genomes of appropriate size, thereby interfering with the maturation of viral particles. Genotypic characterization of letermovir-resistant viruses confirms its action on the viral terminase target.

Letermovir was first approved by the FDA in November 2017 for CMV IgG-positive Allo-HSCT adult recipients to prevent CMV infection. The National Comprehensive Cancer Network (NCCN) Guidelines for Prevention and Treatment of Cancer-Related Infections (2020) recommend letermovir as the primary prophylactic drug for CMV IgG-positive Allo-HSCT recipients, meaning CMV prevention is conducted prior to preemptive treatment measures.