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Transplantation
maribavir due to ganciclovir resistance mutations in UL97 has yet to be caused by other herpesviruses, or perhaps any viruses that carry
observed in laboratory studies, possibly because the drugs interact homologous maribavir targets. The marketed anti-CMV agents have
with different domains of pUL97. In addition to the UL97 gene target, been studied for use in treatment as broad-spectrum antiherpesvirus
resistance of laboratory-generated maribavir variants has also been drugs. The activities of ganciclovir and similar guanosine analogues have
mapped to the CMV UL27 locus, a gene that encodes for a protein of
unknown function.
29
The benefit of maribavir being part of a new class
of compound with a completely novel mechanism of action is that, in
addition to the favourable safety and resistance profiles, maribavir The existing unmet needs have
presents patients with the option of switch therapy.
encouraged research into new drugs
With a mechanism differing from that of the currently available first- for cytomegalovirus that will potentially
and second-line anti-CMV agents, orally bioavailable maribavir is a
have increased efficacy and target
promising new compound in prophylaxis against CMV reactivation and
infection. Preliminary clinical data have shown the drug to have a
specificity, without the limitations of
convenient dosing schedule, as well as high tolerability and efficacy.
the existing compounds.
Furthermore, there are no known cross-resistances between maribavir
and the commonly used anti-CMV drugs to date.
Considerations for Future Research been found to extend to most herpesviruses, including HHV-6.
15,26
If the current clinical trials conclude that maribavir is effective and Cidofovir has also been examined for oral treatment of poxvirus
safe, it would be logical to investigate the use of maribavir in other infections in addition to herpesvirus infections, although cidofovir’s many
disease management settings and for the treatment of other activities result from the less selective nature of its inhibitory action
established diseases. Maribavir is currently available only in oral against viral and host cell polymerases.
27
Maribavir has already been
formulation; it may be worth developing the compound for shown to be active against Epstein-Barr virus (EBV), although the
intravenous administration should that option be one day required. mechanism and exact target have not yet been identified.
28
Other Herpesviruses The existing unmet needs have encouraged research into new
The viral protein kinase pUL97 targeted by maribavir acts across many drugs for CMV that will potentially have increased efficacy and
steps in the viral life cycle. In theory, this should provide a greater target specificity, without the limitations of the existing compounds.
opportunity for the drug to act in different stages of the viral reactivation Given maribavir’s promising clinical trials thus far, this will hopefully
and infection cycle. These aspects have yet to be explored, but lead to the prompt further development of new candidates against CMV infection
idea that maribavir may be effective for the treatment of infections and disease. ■
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46 EUROPEAN HAEMATOLOGY 2007
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