Table II.
Antiherpesviral agents underdevelopment.
| Drug | Antiviral Activity | Mechanism of Action | Study Population/Stage of Study |
|---|---|---|---|
| Brincidofovir | All herpesviruses | Nucleotide analogue–polymerase inhibitor | Phase III study reported increased CMV disease possibly related to increased GVHD.* CMV trials suspended; adenovirus trials ongoing. IV preparation in development |
| Maribavir | CMV | Competitive inhibitor of ATP binding to UL97 protein kinase inhibition of viral encapsidation and nuclear egress of viral particles | Phase III study failed to show efficacy for suppressive therapy to prevent disease post-BMT.122 Ongoing Phase III trial to determine efficacy for treatment of resistant CMV disease in transplant recipients (NCT02931539) |
| Valomaciclovir | HSV VZV EBV |
Nucleoside analogue–polymerase inhibitor | Completed small, randomized, placebo-controlled trial to assess clinical activity for infectious mononucleosis due to EBV. Phase IIb trial for treatment of zoster in adults underway123 |
| N-Methanocarbathymidine | HSV EBV KSHV |
Nucleoside analogue–polymerase inhibitor | Demonstrated superior efficacy in animal models of HSV infection.127,128 Ongoing Phase I trial in healthy volunteers (NCT02778386) |
| Pritelivir (AIC316) | HSV | Helicase-primase inhibitor | In vitro potency superior to acyclovir and effective in animal models of HSV infection.129,130 Completed Phase II trial for treatment of genital herpes.132 Ongoing open-label trial to assess efficacy and safety for treatment of acyclovir-resistant mucocutaneous HSV infection in immunocompromised hosts (NCT03073967) |
| Amenamevir (ASP2151) | HSV VZV |
Helicase-primase inhibitor | Approved for treatment of zoster in Japan in September 2017. In the United States, Phase I trial halted due to safety concerns; no further data available |
ATP = adenosine triphosphate; BMT=bone marrow transplantation; CMV= cytomegalovirus; EBV= Epstein-Barr virus; GVHD = graft-versus-host disease; HSV= herpes simplex virus; IV = intravenous; KSHV= Kaposi’s sarcoma-associated herpesvirus; VZV = varicella zoster virus.
*
Source: Marty FM, Winston DJ, Chemaly RF, Boeckh M, Mullane KM, et al. 2016. Brincidofovir for prevention of cytomegalovirus (CMV) after allogeneic hematopoietic cell transplantation (HCT) in CMV-seropositive patients: a randomized, double-blind, placebo-controlled, parallel-group phase 3 trial [abstract]. Biol Blood Marrow Transplant 22: S23.