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Maribavir
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
Maribavir is an orally bioavailable benzimidazole l-riboside antiviral drug, with a spectrum of activity essentially limited to human cytomegalovirus (CMV) and Epstein-Barr virus (EBV). It is a potent and specific inhibitor of the CMV UL97 kinase. Maribavir is the generic name for 5,6-dichloro-2-(isopropylamino)-1-beta-l-ribofuranosylbenzimidazole, with the chemical structure as shown in Figure 223.1. The molecular weight is 376.24. Investigational drug code names include (BW)1263W94, GW257406X, VP41263, and SHP620 reflecting sequential changes in corporate ownership. Over the past 20 years, maribavir has undergone various clinical trials as an experimental CMV antiviral drug. Earlier phase I and II trials showed anti-CMV activity with an acceptable adverse effect profile. Unsuccessful phase III trials of low-dose maribavir for prevention of CMV infection in transplant patient populations ended in 2009, followed a few years later by phase II CMV treatment trials at higher doses, which were announced as successful in 2015. There is continued clinical interest in this compound because of its distinct antiviral target, oral bioavailability and favorable toxicity profile, although its optimal therapeutic role remains to be determined.
Cytomegalovirus (CMV) Infection
Published in Sunit K. Singh, Daniel Růžek, Neuroviral Infections, 2013
Souichi Yamada, Rumi Taniguchi, Isao Kosugi, Naoki Inoue
Several new types of anti-CMV compounds have been under development (Biron 2006; De Clercq 2003; Fukui et al. 2008; Visalli and van Zeijl 2003). One of the most promising compounds was maribavir, an orally available antiviral drug. Preclinically, it showed advantages over other anti-CMV drugs in its potency; bioavailability; safety profile in acute, chronic, and genetic toxicology testing; and lack of cross-resistance inherent in its novel mechanism of action. In a phase 2 trial on allogeneic SCT patients, maribavir prevented CMV infection significantly (Winston et al. 2008). However, in a phase 3 trial, the drug did not prevent CMV disease when started after engraftment (Marty et al. 2011).
Cytomegalovirus viremia and advanced HIV disease: is there an argument for anti-CMV treatment?
Published in Expert Review of Anti-infective Therapy, 2023
Caleb P. Skipper, Mark R. Schleiss
We are advocating that this question may be worth revisiting in the advanced HIV population given three major developments in the 25 years since the prior studies were completed. First, we have seen the advent of highly effective ART; secondly, we have increased accessibility of CMV viral load monitoring as a risk stratification tool; and third, we have oral valganciclovir, an agent superior to oral ganciclovir. Another exciting development has been the evolution of novel anti-CMV therapeutics. Two new anti-CMV agents are now licensed for use in the United States: letermovir, a drug that works by inhibiting the CMV terminase complex [48], and maribavir, an agent that exerts its antiviral effect via inhibition of the CMV-encoded UL97 kinase [49]. In contrast to ganciclovir (and its prodrug, valganciclovir), these drugs are exceptionally safe and well-tolerated, but do carry drawbacks with respect to the concerns for both cost and the potential for development of antiviral resistance. Letermovir is approved in the United States for prophylaxis against CMV disease in hematopoietic stem cell transplant patients (although data supporting its usefulness as therapy against CMV disease is also published [50–52]). Maribavir is approved for salvage therapy for post-transplant CMV disease that is refractory to ganciclovir, valganciclovir, cidofovir, or foscarnet.
Optimizing the treatment of cytomegalovirus infection in allo-HSCT recipients
Published in Expert Review of Clinical Immunology, 2023
Yu-Qian Sun, Rui Ma, Xiao-Jun Huang
Maribavir inhibits UL97-mediated phosphorylation; thus, it is active against CMV resistance to standard agents. It has the advantages of oral bioavailability and lacks neutropenia and nephrotoxicity. In a randomized, double-blind, phase 2 study from Papanicolaou and colleagues, HSCT and SOT recipients with R/R CMV infections were given maribavir at 3 different doses (400, 800, and 1200 mg twice daily), and 63–70% of patients achieved CMV DNA negativity by week 6 of treatment [59]. The other study from Maertens et al. compared 3 doses of maribavir vs. valganciclovir in treating R/R CMV infections, showing response rates of 79% vs. 67% in the maribavir group and the valganciclovir group, respectively. This study also demonstrated similar antiviral efficacy across doses of maribavir, suggesting that maribavir at 400 mg twice daily was possibly sufficient for eliminating virus from the blood [60]. In a recent phase 3 trial comparing maribavir with investigator-assigned therapy (IAT), 350 patients with R/R CMV infections were enrolled, and 234 of them were given maribavir. By week 8, 55.7% of patients from the maribavir group showed negative CMV DNA in plasma, while at the same time, only 23.9% of patients receiving IAT were negative for plasma CMV DNA (p < 0.001) [61]. Based on current trials, maribavir is promising for treating R/R CMV infections.
Advances in drug therapies for cytomegalovirus in transplantation: a focus on maribavir and letermovir
Published in Expert Opinion on Orphan Drugs, 2020
Jackrapong Bruminhent, R.R. Razonable
Maribavir is a novel investigational drug that is being tested for resistant and refractory CMV infections. Its unique mechanism of action, through UL97 inhibition, allows for its use in CMV strains that have developed resistance to ganciclovir and the DNA polymerase inhibitors. Early phase clinical trials are promising, and phase 3 studies to assess its safety and efficacy are now ongoing. We are optimistic, and in our opinion, maribavir will have a place in CMV management, particularly in the treatment of refractory and resistant CMV infections. However, while it offers a unique mechanism of action, its ability to ensure durable control of infection will rely highly on the recovery of immune function. It is therefore imperative that strategies for viral control are complemented by parallel strategies to ensure immune recovery.