MSD's Antiviral Drug Letermovir Nears Approval in China for CMV Prevention in HSCT Patients

Source: Medicinal Landscape

According to the drug registration progress inquiry on the official website of China's National Medical Products Administration (NMPA), the new drug application for Merck & Co., Inc.’s (MSD) antiviral drug letermovir has entered the "under review" stage, indicating that this product is expected to be approved in China soon. Public information shows that letermovir is a novel non-nucleoside cytomegalovirus (CMV) inhibitor, which was approved by the U.S. FDA in November 2017 for the prevention of CMV infection and related diseases. At that time, it became the first new CMV infection drug approved in the U.S. in 15 years.

Screenshot source: NMPA official website

Cytomegalovirus (CMV) is a common virus that can infect people of all ages. Generally, individuals with a healthy immune system rarely experience CMV symptoms after the initial infection, and the virus usually remains inactive or latent in the body for life. However, when the body's immunity is reduced, 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), which can cause conditions such as gastrointestinal disease, pneumonia, or retinitis, increasing the risk of transplant failure and mortality in patients.

Letermovir is a novel non-nucleoside CMV inhibitor (3,4-dihydroquinazoline). Public data shows that this product has a novel anti-CMV effect. It exerts its antiviral action by inhibiting the activity of the cytomegalovirus terminase complex, thereby preventing the processing and packaging of viral DNA. The difference from DNA polymerase inhibitors is that letermovir has higher selectivity for CMV and significantly enhanced potency.

In China, letermovir was granted implied approval for clinical trials in June 2020, with the proposed indication for development being: prevention of CMV reactivation and disease in CMV-seropositive [R+] adult recipients of allogeneic hematopoietic stem cell transplantation. In November 2020, letermovir submitted four new drug marketing applications in China and received acceptance, including two dosage forms: injection and tablets.

In the United States, the FDA approved letermovir oral tablets and intravenous injection in November 2017 for the prevention of CMV infection and related diseases in adult patients who are CMV-seropositive following allogeneic hematopoietic stem cell transplantation.

According to the results of a Phase 3 clinical trial, among subjects with the aforementioned indications, the proportion of patients in the experimental group who experienced clinically significant CMV infection at Week 24 post-transplant was 18% (vs 42%) compared to the placebo group. Within Week 14 post-transplant, this figure was 8% (vs 39%). The 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.

Note: The original text has been abridged.

References:

[1] China National Medical Products Administration (NMPA) Official Website Drug Registration Progress Inquiry. Retrieved Dec 30, 2021, from http://sq.nmpa.gov.cn/datasearch_nmpa/schedule/search.jsp?tableId=43&tableName=TABLE43&columnName=COLUMN464,COLUMN475&title1=Drug Registration Progress Inquiry

[2] 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

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