Hair transplant — Letermovir proved noninferior to frequent of care in clinical trial
Jeff Minerd, Contributing Author, MedPage Lately
June 6, 2023
Letermovir (Prevymis) proved noninferior to valganciclovir (Valcyte), the frequent of care, in a clinical trial of cytomegalovirus (CMV) prophylaxis in excessive-possibility kidney transplant sufferers, researchers reported.
In a allotment III trial of 589 sufferers randomized 1:1 to receive either drug for up to 200 days post-transplant, the occurrence of CMV disease at 1 year was once now not considerably varied within the letermovir neighborhood versus the valganciclovir neighborhood (10.4% vs 11.8%, adjusted distinction -1.4%, 95% CI -6.5% to three.8%), reported Ajit Limaye, MD, of the University of Washington Treatment in Seattle, and colleagues.
The creep of myelosuppression (leukopenia or neutropenia) at 28 weeks was once considerably decrease with letermovir in contrast with valganciclovir (26% vs 64%, P<0.001), the researchers reported in JAMA.
Furthermore, fewer participants within the letermovir neighborhood discontinued prophylaxis because of the unfavorable events (4.1% vs 13.5%) or drug-associated unfavorable events (2.7% vs 8.8%) in contrast with the valganciclovir neighborhood, the researchers mentioned.
“Cytomegalovirus disease is a considerable reputation off of morbidity and mortality amongst kidney transplant recipients,” Limaye and colleagues wrote. “The incidence is most sensible seemingly within the subgroup of CMV-seronegative kidney transplant recipients who receive an organ from a CMV-seropositive donor, who comprise approximately 20% of all kidney transplant recipients.”
The identical old prophylaxis, valganciclovir, has important limitations, on the opposite hand, the investigators illustrious. It requires dose adjustments, and sufferers had been identified to connect resistance. Furthermore, valganciclovir frequently causes myelosuppression, especially leukopenia and neutropenia, which could lead to discontinuation or necessitate dose reductions of immunosuppressants.
“Letermovir is an antiviral animated in opposition to CMV without associated myelotoxicity, does now not require dose adjustment for kidney impairment, has a favorable mechanism of action as an inhibitor of the CMV DNA terminase advanced, and is never always associated to nefarious-resistance to varied anti-CMV agents,” the look authors mentioned.
Letermovir has limitations of its possess, on the opposite hand, Limaye and colleagues illustrious. Unlike valganciclovir, it does now not admire activity in opposition to herpes simplex virus (HSV) or varicella zoster virus (VZV). And as a sensible cytochrome P3450 3A inhibitor, it has the aptitude to work along with varied drugs.
Letermovir was once accredited by the FDA in 2017 for CMV prophylaxis in CMV-seropositive grownup hematopoietic cell transplant recipients, and has been widely adopted in this population. The drug’s manufacturer, Merck, announced nowadays that the FDA additionally accredited letermovir for CMV prophylaxis in grownup kidney transplant recipients at excessive possibility, in step with outcomes of the original look.
In an editorial accompanying the look, Zoe Raglow, MD, and Daniel R. Kaul, MD, each and every of the University of Michigan Scientific College in Ann Arbor, mentioned one more limitation of letermovir is its price. “Fee will undoubtedly be a ingredient, attributable to the sensible day-to-day price of letermovir (approximately $250 per day) is better than 20 times that of generic valganciclovir, making it one of basically the costliest routine post-transplant medications,” they wrote.
Nevertheless, Raglow and Kaul mentioned the outcomes offered by Limaye’s neighborhood were “relate changing,” and clinicians will prefer to weigh the limitations and advantages of letermovir in bearing in thoughts the sufferers mostly liable to earnings. “Letermovir could maybe maybe maybe be most price-effective when feeble amongst sufferers with baseline leukopenia or who attach leukopenia at some point soon of valganciclovir remedy,” the editorialists suggested.
The double-blind, double-dummy allotment III trial integrated the most sensible seemingly-possibility grownup sufferers: CMV-seronegative kidney transplant recipients who bought an organ from a CMV-seropositive donor. The bulk were white (84%) and male (71%).
The letermovir neighborhood bought 480 mg of letermovir orally day-to-day, 400 mg of acyclovir twice day-to-day (as HSV and VZV prophylaxis), and a valganciclovir placebo. The valganciclovir neighborhood bought 900 mg of valganciclovir orally day-to-day with placebos for letermovir and acyclovir. Acyclovir does now not admire activity in opposition to CMV, the researchers illustrious.
The well-known was once CMV disease, confirmed by an self sustaining masked adjudication committee, through post-transplant week 52, with a prespecified noninferiority distinction of 10%. The creep of leukopenia or neutropenia through week 28 was once a prespecified safety .
Secondary outcomes integrated CMV disease through week 28 and time to onset of CMV disease. No participants within the letermovir neighborhood developed CMV disease through week 28 versus five participants who bought valganciclovir. The time to onset of CMV disease was once similar between the groups (HR 0.90, 95% CI 0.56-1.47).
Look limitations, the team mentioned, integrated that myelotoxicity was once evaluated as leukopenia or neutropenia, but valganciclovir can also reputation off anemia and thrombocytopenia. There was once additionally no price prognosis, despite price being a compulsory consideration with letermovir.
As effectively as, the look lacked diversity, the authors mentioned, despite the incontrovertible truth that CMV disease possibility has now not been linked to gender, scuttle, or ethnicity. No longer at this time, long-term outcomes of CMV disease weren’t formally assessed. “Nevertheless, attributable to CMV disease was once similar between groups, there could be no reason to wait for variations in long-term outcomes with letermovir versus valganciclovir,” the researchers mentioned.
Jeff Minerd is a contract clinical and science author basically based mostly mostly in Rochester, NY.
The look was once funded by Merck Racy & Dohme.
Limaye reported relationships with Merck, Moderna, NobelPharma, Takeda, AiCuris, Vera, AlloVir, and GSK; varied co-authors reported relationships with alternate, along side employment with Merck.
Kaul reported financial relationships with Takeda, NobelPharma, and Medscape; Raglow reported no conflicts of pastime.
Provide Reference: Limaye AP, et al “Letermovir vs valganciclovir for prophylaxis of cytomegalovirus in excessive-possibility kidney transplant recipients: a randomized clinical trial” JAMA 2023; DOI: 10.1001/jama.2023.9106.
Provide Reference: Raglow Z, Kaul DR “A original antiviral option for cytomegalovirus prevention after kidney transplant” JAMA 2023; DOI:10.1001/jama.2023.9100.