Prevymis(letermovir)口服和静脉注射-每日一次預防CMV感染的新葯
CMV是一种常见病毒，可感染所有年龄段人群。在美国，许多成人CMV血清反应呈阳性，意味着他们之前曾接触过CMV或原发感染CMV，使血液中含有CMV抗体。
　免疫系统正常的人在初次感染之后很少发生CMV症状，病毒通常保持无活性或潜伏在体内一生。免疫系统降低可能会使病毒有机会重新激活，导致症状性疾病或由其他病原体引起的继发性感染。
　2017年11月13日，默沙东（MSD）宣布，FDA批准了PREVYMI（letermovir）口服片剂和静脉注射液，在接受异基因造血干细胞移植（HSCT）后，巨细胞病毒（CMV）血清呈阳性的成人患者中，预防CMV感染和相关疾病。
　关于PREVYMIS：
　PREVYMIS是一种新型非核苷CMV抑制剂（3,4-二氢喹唑啉），通过特异性靶向病毒终止酶复合物来抑制病毒复制。它与非同类药物不易存在交叉耐药性。
　PREVYMIS对CMV耐DNA聚合酶抑制剂的病毒群体完全有活性，而DNA聚合酶抑制剂对耐PREVYMIS的病毒群体也有活性。
　PREVYMIS对其他病毒没有活性。在美国，欧盟和日本，Letermovir被授予孤儿药资格预防巨细胞病毒疾病，并正在欧盟和日本加速审查。
　相关研究：
  为评估PREVYMIS作为预防高危移植患者CMV感染或CMV重新激活疾病的策略，多中心，双盲，安慰剂对照的3期临床试验在CMV血清阳性异基因HSCT的成人移植患者中，评估了PREVYMIS的预防有效性。
　患者被随机按2：1分配，接受PREVYMIS或安慰剂。PREVYMIS组患者每日一次接受480毫克药物，当与环孢菌素共同使用时调整至240毫克。研究药物在HSCT后（在移植后0-28天内）开始，直到移植后的第14周。
　研究监测患者在移植24周后的主要疗效终点，并在移植后48周后随访。主要疗效终点为移植后24周发生的临床上显着的CMV感染事件（定义为发生CMV终末器官疾病，或者基于患者CMV病毒血症和临床状况，开始进行抗CMV先发性治疗）。治疗未完成等于失败，在移植后第24周之前停止试验或在移植后24周结果缺失的患者也被统计为失败。 
   在这项关键性3期临床试验中，PREVYMIS组（38％，n = 122/325）与安慰剂组（61％，n = 103/170）相比， 临床显着的CMV感染，终止治疗，或在HSCT后24周数据缺失[治疗差异：-23.5（95％置信区间-32.5至-14.6），（p <0.0001）]明显减少。接受prevymis治疗的患者与接受安慰剂的患者相比，全因死亡率分别为12％和17％。在这项研究中，prevymis组的骨髓抑制发生率与安慰剂组相当。prevymis组的中位移植时间为19天，安慰剂组为18天。
Prevymis Approved for Prevention of Cytomegalovirus Infection and Disease
Merck announced that the Food and Drug Administration (FDA) has approved Prevymis (letermovir) tablets and intravenous (IV) injection for prophylaxis of cytomegalovirus (CMV) infection and disease in adult CMV-seropositive recipients (R+) of an allogeneic hematopoietic stem cell transplant (HSCT).
The FDA approval was based on data from a Phase 3 multicenter, double-blind, placebo-controlled trial (n=565) in adult CMV R+ patients of an allogeneic HSCT who were randomized to Prevymis 480mg once daily (adjusted to 240mg for concomitant drugs) or placebo. Patients were monitored up to Week 24 post-transplant for the incidence of clinically significant CMV infection, and then further monitored through Week 48 post-transplant.
The data showed significantly fewer patients treated with Prevymis vs. placebo (38% vs. 61%) developed clinically significant CMV infection, stopped treatment or had missing data through Week 24 post-HSCT (difference –23.5, 95% CI: –2.5 to –14.6; P<0.0001). A significant benefit was seen with Prevymis vs. placebo in time to clinically significant CMV infection through Week 24 post-HSCT (cumulative rate: 18.9% vs. 44.3%; P<0.0001). 
All-cause mortality was also lower in Prevymis-treated patients vs placebo at Week 24 post-transplant (12% vs. 17%). Bone marrow suppression occurrence was similar for both groups. In addition, the median time to engraftment was 19 days in the Prevymis treatment arm vs. 18 in the placebo arm.
Prevymis, a non-nucleoside CMV inhibitor (3,4 dihydro-quinazoline), inhibits viral replication through targeting the viral terminase complex. Prevymis will be available as 240mg and 480mg strength tablets in 4 Dosepaks, each containing a 7-count blister card (28 tablets total) or as a carton containing 2 blister cards, each containing a 7-count blister card (14 tablets total). Prevymis injection will be available in 240mg  (12mL vial) and 480mg (24mL vial) strengths in single-dose vials. Both formulations are anticipated to launch in December.