MSD Submits NDA for Letermovir in China, the First New Anti-CMV Therapy in 15 Years

On November 18, the latest public announcement from the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration revealed that MSD’s antiviral drug letermovir had submitted four new drug marketing applications, which were accepted, including two formulations: injection and tablets. Notably, this drug was approved by the U.S. FDA in November 2017 for the prevention of cytomegalovirus (CMV) infection and related diseases. According to a press release previously issued by MSD, letermovir is the first new drug approved in the United States in 15 years for the treatment of CMV infection.

Screenshot source: CDE official website

Cytomegalovirus (CMV) is a common virus that can infect individuals of all ages. Typically, immunocompetent individuals rarely exhibit symptoms after primary infection, and the virus usually remains inactive or latent in the body for life. However, when immune function is compromised, the virus may reactivate, leading to symptomatic disease or secondary infections caused by other pathogens. Clinically, CMV infection is one of the common complications in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT), potentially causing conditions such as gastrointestinal disease, pneumonia, or retinitis, thereby increasing the risk of graft failure and mortality.

Letermovir is a novel non-nucleoside CMV inhibitor (3,4-dihydroquinazoline). Publicly available data indicate that this product exhibits a novel anti-CMV mechanism of action by inhibiting the activity of the cytomegalovirus terminase complex, thereby blocking viral DNA processing and packaging and exerting its antiviral effect. Unlike DNA polymerase inhibitors such as ganciclovir and foscarnet sodium, letermovir demonstrates higher selectivity for CMV and significantly greater potency.

▲ Molecular structure of letermovir (Image source: Wikipedia)

In China, letermovir received four implicit approvals for clinical trials from the CDE in June this year. The proposed indications are for the prevention of CMV reactivation and disease in adult recipients [R+] who are cytomegalovirus seropositive undergoing allogeneic hematopoietic stem cell transplantation.

In the United States, the European Union, and Japan, letermovir was granted orphan drug designation for the prevention of cytomegalovirus disease. In November 2017, the FDA approved letermovir oral tablets and intravenous injection for the prevention of CMV infection and related diseases in adult patients who are CMV-seropositive following allogeneic hematopoietic stem cell transplantation.

According to a multicenter, double-blind, placebo-controlled Phase 3 clinical trial conducted in adult allogeneic hematopoietic stem cell transplantation (HSCT) recipients who were cytomegalovirus (CMV) seropositive, the primary efficacy endpoint was the incidence of clinically significant CMV infection at Week 24 post-transplantation. The results showed that among 565 treated patients, the proportion of patients in the experimental group who developed clinically significant CMV infection at Week 24 post-transplantation was 18% (vs. 42% in the placebo group). Within the first 14 weeks post-transplantation, this figure was 8% (vs. 39%). Efficacy outcomes were consistent across both high-risk and low-risk populations for CMV reactivation. Additionally, the all-cause mortality rates were 12% in the experimental group and 17% in the placebo group.

According to a press release previously issued by MSD, study results demonstrated that letermovir prevented clinically significant cytomegalovirus (CMV) infection in susceptible patient populations, achieving significant progress in reducing mortality. Executives at Merck Research Laboratories noted that letermovir is the first new drug approved in the United States for CMV infection in 15 years, continuing MSD’s long-standing tradition of providing important new therapies to address serious infectious diseases.

References

[1] Center for Drug Evaluation, National Medical Products Administration of China. Retrieved Nov 18, 2020, from http://www.cde.org.cn/news.do?method=changePage&pageName=service&frameStr=21#

[2] Yang Junyi, Zhang Liju. (2019). A New Drug for the Prevention of Cytomegalovirus Infection: Letermovir. Chinese Journal of New Drugs and Clinical Remedies, 17-19. doi:CNKI:SUN:XYYL.0.2019-05-003.

[3] Merck Receives FDA Approval of PREVYMIS™ (letermovir) for Prevention of Cytomegalovirus (CMV) Infection and Disease in Adult Allogeneic Stem Cell Transplant Patients. Retrieved Nov 09，2017, from https://www.businesswire.com/news/home/20171109005397/en/Merck-Receives-FDA-Approval-PREVYMIS

Source: Medical Horizon

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