The objective of the trial was to compare letermovir with valganciclovir in the prevention of CMV disease in adults who received a kidney transplant and who are at high risk of CMV disease.
Letermovir (Prevymis, Merck) was effective and noninferior to valganciclovir in preventing cytomegalovirus (CMV) in a phase 3 trial that evaluated the drug’s safety and efficacy.
The trial, which enrolled 601 adult kidney transplant recipients at high risk for CMV disease, met the primary endpoint at 52 weeks after kidney transplantation by demonstrating the efficacy of letermovir and its non-inferiority to valganciclovir for prevent CMV disease. Additionally, in a prespecified safety analysis, patients given letermovir had significantly less myelotoxicity, as measured by rates of leukopenia or neutropenia, compared with patients given valganciclovir 26.0% (n =76) vs. 64.0% (n=190), (95% CI, -45.1, -30.3; p-value <0.0001).
“CMV disease is a major cause of morbidity and mortality in kidney transplant recipients. Valganciclovir has been the most widely used drug for CMV prophylaxis in this setting, but myelotoxicity (especially neutropenia and leukopenia) is a major limitation of this drug. Myelotoxicities can be difficult to manage in patients who are already receiving complex treatment regimens with other medications that also have bone marrow suppressive effects,” said Ajit P. Limaye, MD, director of the Solid Organ Transplant Infectious Diseases Program. from the University of Washington School of Medicine. , in a press release. “I was excited to see the results of these trials showing that the efficacy of Prevymis in preventing CMV disease in kidney transplant patients was similar to current standard therapy (valganciclovir), but with significantly less toxicity.”
The objective of the trial was to compare letermovir with valganciclovir in the prevention of CMV disease in adults who received a kidney transplant and who are at high risk of CMV disease. Participants were randomized to receive letermovir 480 mg once daily or valganciclovir 900 mg once daily within 7 days post-kidney transplant until 28 weeks post-transplant, with a 52-week follow-up. Participants were classified according to the use and non-use of lymphocyte-depleting induction immunotherapy.
Results showed that 10.4% (n=30) of patients given letermovir developed CMV disease compared to 11.8% (n=35) of patients given valganciclovir ( adjusted difference by stratum = -1.4, [95% CI, -6.5, 3.8]).
For the trial’s secondary endpoint of adjudicated CMV disease at 28 weeks post-transplant, 0% (n=0) of patients receiving letermovir and 1.7% (n=5) of patients receiving valganciclovir had CMV disease (stratum-adjusted difference = -1.7 [95% CI, -3.4, 0.1]).
Letermovir showed a favorable safety profile over valganciclovir, with fewer drug-related adverse events (AEs) and study drug discontinuations due to AEs in the letermovir group versus the valganciclovir group.
Other safety findings showed that neutropenia measured during treatment up to week 28 post-transplant was 4.1% in the letermovir group compared to 19.5% in the valganciclovir group. Incidents of leukopenia and neutropenia leading to letermovir discontinuation during the 28-week treatment phase were 1.0% in the letermovir group vs. 5.4% in the valganciclovir group, and 1.4% in the letermovir group versus 1.7% in the valganciclovir group.
Letermovir is a first-in-class antiviral agent approved by the FDA in 2017 for the prophylaxis of CMV infection and disease in CMV-seropositive adult patients who received an allogeneic hematopoietic stem cell transplant. Letermovir is contraindicated in patients receiving pimozide or ergotamine alkaloids.
“There is a need for additional CMV prophylactic options for kidney transplant recipients to help patients reduce the risk of opportunistic infections,” said Nicholas Kartsonis, MD, senior vice president, vaccines and infectious diseases, Global Clinical Development, Merck Research Laboratories, in a press release. release. “The results of this new study in adult kidney transplant patients are encouraging and demonstrate the potential of PREVYMIS to prevent CMV disease with a therapy that showed lower rates of neutropenia and leukopenia compared to comparator.”
Merck’s PREVYMIS™ Demonstrates Efficacy in a Phase 3 Study for the Prevention of Cytomegalovirus Disease in Adults After Kidney Transplantation. Merck. October 22, 2022. Retrieved October 24, 2022. https://www.merck.com/news/mercks-prevymis-demonstrates-efficacy-in-phase-3-study-for-prevention-of-cytomegalovirus-disease-in-adults-after-kirney-transplantation/