“Three-day or single-day courses of ASP2151 appear to be effective and safe options for treatment of episodes of recurrent genital herpes,” conclude Ramona L. Rorig, with Astellas Pharma Global Development in Deerfield, Illinois, and colleagues.
They explain that ASP2151 targets the viral helicase-primase complex, which is essential for herpes simplex virus DNA synthesis. The team tested various doses of the drug against placebo and valacyclovir in a double-blind randomized trial involving 695 adults with episodic recurrence of genital herpes.
Specifically, the participants were assigned to ASP2151 at a daily dose of 100, 200, or 400 mg for 3 days, ASP2151 as a single dose of 1200 mg, placebo for 3 days, or valacyclovir 500 mg twice daily for 3 days. Blinding was maintained with matching placebo pills as needed.
The patients initiated treatment at the first sign or symptom of a herpes recurrence, and the primary efficacy endpoint was time to lesion healing excluding aborted lesions.
Median healing times were 139.8 hours with placebo, 119.6 hours with ASP2151 100 mg (hazard ratio [HR], 1.40; p=0.065), 106.2 with ASP2151 200 mg (HR, 1.40; p=0.081), 115.9 with ASP2151 400 mg (HR, 1.25; p=0.25), 102.1 with ASP2151 1200 mg (HR, 1.72; p=0.007), and 113.9 with valacyclovir 500 mg twice daily (HR, 1.42; p=0.077), the researchers report.
“The duration of viral shedding and the duration of the episode were each 2 days shorter in all the ASP2151 groups, compared with the placebo group,” they note.
Most treatment-emergent events were mild or moderate and most related to GI complaints. However, one patient developed tachycardia, pyrexia and tremor on day 1 of treatment and another also discontinued because of abdominal pain, dizziness and lethargy on day 3.
The authors conclude that helicase primase inhibitors “offer an alternative therapeutic approach for patients who have acyclovir-resistant HSV or for whom standard therapy with nucleoside analogues has not resulted in adequate response.”
They add, “ASP2151 administered alone or in combination with other antivirals may provide a treatment alternative for immunocompromised participants who have infection with HSV that is resistant to nucleoside analogues; however, its efficacy in this patient population remains to be explored.”
J Infect Dis 2012.