March 21, 2012 (San Diego, California) — A novel helicase-primase inhibitor with antiviral activity against the varicella zoster virus might provide an alternative as potent as current treatments for the genital herpes simplex virus (HSV), according to a phase 2 study presented as a late-breaking study here at the American Academy of Dermatology 70th Annual Meeting.
The findings are important because HSV resistance to oral nucleoside analogues, such as valacyclovir and acyclovir, is a problem, and the current alternative, foscarnet, has adverse effects and requires intravenous administration, explained presenter Rachel Gordon, MD, from the Center for Clinical Studies at the University of Texas in Houston.
The randomized, blinded, proof-of-concept trial compared the safety and efficacy of a helicase-primase inhibitor known as ASP2151 with valacyclovir and placebo for the treatment of recurrent genital herpes.
Among the 695 adults enrolled, 437 (mean age, 40 years; 70% female) had a recurrence of genital herpes and were randomized to receive 1 of 4 doses of ASP2151 (100, 200, 400, or 1200 mg) or valacyclovir 500 mg or placebo twice daily for 3 days.
To meet the eligibility criteria, patients had to have had at least 4 episodes of recurrent genital herpes in the previous 12 months and had to have received no suppressive therapy for the last recurrence.
Almost half of the cohort (49%) was infected with HSV-2, 43% was infected with both HSV-1 and HSV-2, and the remainder was infected with HSV-1.
The primary study outcome — median number of hours to lesion healing — was similar for all doses of ASP2151 (120 hours for 100 mg, 106 hours for 200 mg, 116 hours for 400 mg, and 102 hours for 1200 mg) and valacyclovir (114 hours); all treatments were superior to placebo (140 hours), said Dr. Gordon.
Compared with placebo, the hazard ratios (HR) for the ASP2151 regimens were 1.40 for both the 100 mg and 200 mg doses, 1.25 for the 400 mg dose, and 1.72 for the 1200 mg dose; for valacyclovir, the HR was 1.42.
There were no severe adverse reactions, and the most common adverse effects in the ASP2151 groups were nausea, dizziness, and headache.
Asked to comment on the findings, Maria Hordinsky, MD, who was on the selection committee for the late-breaking abstracts, told Medscape Medical News that there is a great interest in finding an alternative to antivaricella zoster virus therapies; the selection committee viewed many abstracts on this topic.
"We already have really good drugs — we have acyclovir and valacyclovir — so why do we need a helicase-primase inhibitor? It's all about new choices," said Dr. Hordinsky, who is professor and chair of the Department of Dermatology at the University of Minnesota Medical School in Minneapolis. "The main point here is that some people are developing resistance to the standard treatments, so you need new options."
Helicase-primase inhibitors circumvent the reliance that nucleoside analogues have on the phosphorylation of viral thymidine kinase, explained Dr. Gordon. "There do exist HSV strains that have dysfunctional thymidine kinase and are immune to oral nucleoside analogues."
The study was sponsored by Astellas Pharma. Dr. Gordon has disclosed no relevant financial relationships. Dr. Hordinksy reports receiving investigator grants from Astellas Pharma US, Allergan, Johnson & Johnson Consumer Products, Lexington International, Medicis Pharmaceutical, and Novartis Pharmaceuticals.
American Academy of Dermatology (AAD) 70th Annual Meeting: Late-breaking abstract. Presented March 16, 2012.
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Cite this: Helicase-Primase Inhibitor: New Tool Against Genital Herpes? - Medscape - Mar 21, 2012.