The Food and Drug Administration (FDA) has approved Prevymis® (letermovir) for prophylaxis of cytomegalovirus (CMV) disease in adult kidney transplant recipients at high risk (donor CMV seropositive/recipient CMV seronegative [D+/R-]).
The approval was supported by data from a phase 3 trial (ClinicalTrials.gov Identifier: NCT03443869) that evaluated the efficacy and safety of letermovir to prevent CMV disease in adult kidney transplant recipients at high risk.
Patients were randomly assigned to receive either letermovir 480mg orally once daily concomitantly with acyclovir (n=289), or valganciclovir 900mg orally once daily concomitantly with a placebo to acyclovir (n=297), within 7 days post-kidney transplant through 28 weeks post-transplant, with follow-up through 52 weeks.
At 52 weeks, treatment with letermovir was found to be effective and noninferior to valganciclovir; 10% of patients in the letermovir arm developed CMV disease vs 12% of patients in the valganciclovir arm (stratum adjusted difference, -1.4 [95% CI, -6.5, 3.8]).
The incidence of CMV syndrome (defined as evidence of CMV in blood by viral isolation, rapid culture, antigenemia, or nucleic acid testing, and ≥2 of the following: 1) fever ≥38°C for at least 2 days, 2) new or increased malaise/fatigue, 3) leukopenia or neutropenia on 2 separate measurements at least 24 hours apart, 4) ≥5% atypical lymphocytes, 5) thrombocytopenia, 6) elevation of ALT or AST to 2x ULN) was 8% and 11% in the letermovir and valganciclovir arms, respectively.
Efficacy was found to be comparable across all subgroups, including those who used or did not use highly cytolytic, antilymphocyte immunotherapy during induction.
Exploratory findings showed that the difference in the incidence of CMV disease through week 28 post-transplant between the letermovir and valganciclovir groups was -1.7% (95% CI, -3.4, 0.1). Through week 28 post-transplant, 5 cases of CMV disease were reported in the valganciclovir group vs no cases in the letermovir group.
The most common adverse reaction reported with letermovir (at a frequency greater than valganciclovir) was diarrhea.
Prevymis is supplied as 240mg and 480mg tablets and in single-dose vials of 240mg/12mL and 480mg/12mL. In the clinical trial, Prevymis was administered either orally or intravenously.
Dosage adjustments are required if Prevymis is coadministered with cyclosporine. Monitoring for CMV reactivation following the completion of Prevymis prophylaxis is recommended.
Prevymis is also indicated for prophylaxis CMV infection and disease in adult CMV-seropositive recipients [R+] of an allogeneic hematopoietic stem cell transplant.
- US FDA approves new indication for Merck’s Prevymis® (letermovir) for prevention of cytomegalovirus (CMV) disease in high-risk adult kidney transplant recipients. News release. June 6, 2023. https://www.businesswire.com/news/home/20230606005563/en/U.S.-FDA-Approves-New-Indication-for-Merck%E2%80%99s-PREVYMIS%C2%AE-letermovir-for-Prevention-of-Cytomegalovirus-CMV-Disease-in-High-Risk-Adult-Kidney-Transplant-Recipients.
- Prevymis. Package insert. Merck; 2023. Accessed June 6, 2023. https://www.merck.com/product/usa/pi_circulars/p/prevymis/prevymis_pi.pdf.