The US FDA approved letermovir for prevention of cytomegalovirus (CMV) infection and disease in adult allogeneic hematopoietic stem cell transplant (HSCT) recipients. The drug has a novel mechanism of action through inhibition of the CMV DNA terminase complex. The registration trial compared letermovir to placebo in CMV-positive adult HSCT recipients. Treatment/placebo began within 28 days after transplant and continued until 100 days posttransplant. The primary endpoint was CMV disease or viremia leading to preemptive antiviral administration. Of 495 participants analyzed, among those who remained on drug, clinically significant CMV infection occurred in 18% on letermovir and 42% on placebo by week 24 — a significant difference.
Gastrointestinal symptoms, edema, and cardiac arrhythmias were more common in letermovir-treated subjects. Multiple CYP3A and OATP1B1/3 mediated drug interactions may occur; in particular, when the drug is coadministered with cyclosporine (but not with tacrolimus), a 50% reduction in letermovir dosing is required. Oral and intravenous formulations are available.