Letermovir Shows Efficacy Preventing Cytomegalovirus Disease in Adults After Kidney Transplantation

The objective of the trial was to compare letermovir with valganciclovir in preventing CMV disease in adults who received a kidney transplant and who are at high risk for CMV disease.

Letermovir (Prevymis, Merck) was found effective and non-inferior compared to valganciclovir in preventing cytomegalovirus (CMV) in a phase 3 trial assessing the safety and efficacy of the drug.

The trial, which enrolled 601 adult kidney transplant recipients at high risk for CMV disease, met the primary endpoint at 52 weeks following kidney transplant in demonstrating the efficacy of letermovir as well as its non-inferiorty to valganciclovir for preventing CMV disease. Further, in a pre-specified safety analysis, patients administered letermovir had significantly less myelotoxicity, as measured by rates of leukopenia or neutropenia, compared with patients administered valganciclovir at 26.0% (n=76) versus 64.0% (n=190), (95% CI, -45.1, -30.3; p-value <0.0001).

“CMV disease is an important cause of morbidity and mortality in kidney transplant recipients. Valganciclovir has been the most commonly used drug for CMV prophylaxis in this setting, but myelotoxicity (especially neutropenia and leukopenia) is an important limitation of this drug. Myelotoxicities can be difficult to manage in patients who are already receiving complex treatment regimens with other drugs that also have bone marrow suppressive effects,” said Ajit P. Limaye, MD, director, Solid Organ Transplant Infectious Disease Program at University of Washington School of Medicine, in a press release. “I was excited to see these trial results that showed that the efficacy of Prevymis for prevention of CMV disease in kidney transplant patients was similar to the current standard of care treatment (valganciclovir), but with significantly less toxicity.”

The objective of the trial was to compare letermovir with valganciclovir in preventing CMV disease in adults who received a kidney transplant and who are at high risk for CMV disease. The participants were randomized to receive either 480 mg of letermovir once a day or 900 mg of valganciclovir once a day within 7 days post-kidney transplant through 28 weeks post-transplant, with follow-up through 52 weeks. The participants were ranked by use and non-use of lymphocyte-depleting induction immunotherapy.

The results showed that 10.4% (n=30) of patients administered letermovir developed CMV disease compared with 11.8% (n=35) of patients administered valganciclovir (stratum adjusted difference = -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 administered letermovir and 1.7% (n=5) of patients administered valganciclovir had CMV disease (stratum adjusted difference = -1.7 [95% CI, -3.4, 0.1]).

Letermovir showed a favorable safety profile to 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 neutropenia measured during treatment through week 28 post-transplant was in 4.1% of the letermovir group compared with 19.5% of the valganciclovir group. Incidents of leukopenia and neutropenia that led to discontinuation of letermovir during the 28-week treatment phase was 1.0% in the letermovir group vs 5.4% in the valganciclovir group, and 1.4% in the letermovir group vs 1.7% in the valganciclovir group.

Letermovir is a first-in-class antiviral agent approved by the FDA in 2017 for prophylaxis of CMV infection and disease in adult CMV-seropositive patients who received an allogeneic hematopoietic stem cell transplant. Letermovir is contraindicated in patients receiving pimozide or ergot alkaloids.

“There is a need for additional CMV prophylactic options for kidney transplant recipients to help patients reduce 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. “These new study results 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 versus the comparator.”

REFERENCE

Merck’s PREVYMIS™ Demonstrates Efficacy in Phase 3 Study for Prevention of Cytomegalovirus Disease in Adults After Kidney Transplantation. Merck. October 22, 2022. Accessed October 24, 2022. https://www.merck.com/news/mercks-prevymis-demonstrates-efficacy-in-phase-3-study-for-prevention-of-cytomegalovirus-disease-in-adults-after-kidney-transplantation/