MSD's Antiviral Drug Letermovir Injection Approved in China for CMV Prevention in Allogeneic HSCT Patients

Today, the official website of China's National Medical Products Administration (NMPA) announced that the injectable form of MSD's antiviral drug letermovir has been approved for marketing in China. Notably, the tablet form of this drug was approved in China in January this year for the prophylactic treatment of cytomegalovirus.

Screenshot source: NMPA official website

Cytomegalovirus (CMV), a widely present herpesvirus, poses a severe threat to the health and lives of hematopoietic stem cell transplantation (HSCT) patients. Studies have shown that among these patients, the CMV seropositivity rate can be as high as 92%, with viral reactivation rates ranging from 30% to 80%. According to an earlier press release by MSD, prior to the advent of letermovir, there were no globally approved drugs for the prevention of CMV infection following allogeneic HSCT. Although preemptive therapy is an effective method for controlling CMV, many allogeneic HSCT recipients still encounter issues with refractory CMV infections. Moreover, the medications used in preemptive therapy carry adverse effects such as myelosuppression and nephrotoxicity, increasing patient mortality risks and healthcare burdens.

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 November 2020, letermovir submitted four new drug applications in China and was accepted, including two formulations: injection and tablets. In January 2022, the tablet formulation of letermovir (brand name Prevymis) was approved in China for the prevention of cytomegalovirus (CMV) infection and CMV disease in adult recipients [R+] who are CMV-seropositive and have received allogeneic hematopoietic stem cell transplantation. In the United States, the FDA approved letermovir oral tablets and intravenous injection in November 2017 for CMV-seropositive adult patients after allogeneic HSCT to prevent CMV infection and related diseases.

According to a previous press release from MSD, in the pivotal Phase 3 clinical trial supporting the FDA approval of letermovir, there was a significant reduction in clinically significant CMV infections, treatment discontinuations, or missing data at 24 weeks post-HSCT in the letermovir group (38%, n=122/325) compared to the placebo group (61%, n=103/170), reaching the primary efficacy endpoint. At 24 weeks post-transplant, the all-cause mortality rate was 12% for patients treated with letermovir and 17% for those receiving placebo. Additionally, the incidence of myelosuppression in the letermovir group was comparable to that of the placebo group. The median transplant time was 19 days for the letermovir group and 18 days for the placebo group.

References:

[1] Drug Approval Certificate Pending Collection Information Released on May 13, 2022. Retrieved May 13, 2022, from https://www.nmpa.gov.cn/zwfw/sdxx/sdxxyp/yppjfb/20220513124639174.html

[2] MSD’s Prevymis® (Letermovir Tablets) Approved by China’s National Medical Products Administration for Prophylactic Treatment of Cytomegalovirus. Retrieved Jan 6, 2022. From https://mp.weixin.qq.com/s/ySTD7QkCtzqpAnACALVmGQ

[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 9 , 2017. From https://www.merck.com/news/merck-receives-fda-approval-of-prevymis-letermovir-for-prevention-of-cytomegalovirus-cmv-infection-and-disease-in-adult-allogeneic-stem-cell-transplant-patients/

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