FDA Approval Announcement
According to a press release from Merck & Co., Inc. dated June 6, the U.S. Food and Drug Administration (FDA) has approved an expanded indication for Prevymis (letermovir) for the prevention of cytomegalovirus (CMV) disease in high-risk adult kidney transplant recipients (donor CMV-seropositive / recipient CMV-seronegative [D+/R-]).
Mechanism of Action and Initial Approval
Mechanism of Action
Prevymis is an antiviral agent belonging to a novel class of non-nucleoside CMV inhibitors (3,4-dihydroquinazolines). It inhibits viral replication by targeting the viral terminase complex.
Initial Approval
Prevymis was first approved by the FDA in 2017 for the prevention of CMV infection and disease in CMV-seropositive adult recipients [R+] of allogeneic hematopoietic stem cell transplantation (HSCT).
Dosage and Administration
Route of administration: Oral tablets or intravenous injection
Recommended dosage: 480 mg once daily
Duration: Initiation between Day 0 and Day 7 after kidney transplantation, continued through Day 200 post-transplantation
Dose adjustment with cyclosporine: If administered concomitantly with cyclosporine, reduce the dose to 240 mg once daily (oral or intravenous).
Basis for Approval: Phase 3 Trial (NCT03443869)
The approval was supported by data from a Phase 3 trial evaluating the efficacy and safety of Prevymis for CMV prophylaxis in high-risk adult kidney transplant recipients.
Study Design
Randomized trial comparing 480 mg Prevymis plus acyclovir (n=289) versus 900 mg valganciclovir plus placebo plus acyclovir (n=297)
Treatment period: from Day 7 through Week 28 post-transplantation
Follow-up duration: 52 weeks
Key Efficacy Results
At Week 52, Prevymis demonstrated efficacy and non-inferiority compared to valganciclovir.
CMV disease incidence:
Prevymis group: 10%
Valganciclovir group: 12%
Stratified adjusted difference: -1.4 (95% CI: -6.5, 3.8)
Efficacy was consistent across all subgroups, including those receiving or not receiving high-lymphocytotoxic anti-lymphocyte induction therapy.
Exploratory Outcomes
At Week 28 post-transplantation, the difference in CMV disease incidence between the Prevymis and valganciclovir groups was -1.7% (95% CI: -3.4, 0.1).
No cases of CMV disease were reported in the Prevymis group at Week 28, compared with 5 cases in the valganciclovir group.
Safety Profile
The most commonly reported adverse reaction was diarrhea.
