Healing times for recurrences of herpes simplex virus 2 (HSV-2) for patients treated with ASP2151 were significantly better than placebo and were comparable to valacyclovir, based on the results of a phase-II randomized, double-blind study of 437 patients. The results were presented at the annual meeting of the American Academy of Dermatology.
The United States seroprevalence of HSV-2 is 16% among people aged 14-49 years. "Unlike other sexually-transmitted diseases that affect persons with a high level of sexual activity, HSV-2 affects even those with moderate-to-low sexual activity. It’s estimated that 18% of American women with a total of two to four lifetime sexual partners are seropositive for HSV-2," said Dr. Rachel Gordon of the Center for Clinical Studies at the University of Texas in Houston.
HSV is associated with significant morbidity and mortality. For example, those with genital herpes have a three-fold increased risk of acquiring HIV.
The current standard of care for these infections is the use of oral nucleoside analogues, such as valacyclovir (Valtrex). However, these drugs have some drawbacks. Their antiviral effect is dependent on the phosphorylation of viral thymidine kinase. "We know that viral replication can occur in the absence of viral thymidine kinase. In addition, there do exist HSV strains that have dysfunctional thymidine kinase that are immune to oral nucleoside analogues," said Dr. Gordon. "We know that sexual transmission does occur during suppressive therapy."
Helicase primase inhibitors target the virus helicase-primase complex, which is involved in DNA replication. In vitro studies have shown helicase-primase inhibitors to be more potent antivirals against both HSV-1 and HSV-2, compared with valacyclovir.
The researchers included 695 healthy adults with recurrent genital herpes. Of those, 437 (63%) experienced a recurrence and received treatment with ASP2151 (in doses of 100 mg, 200 mg, 400 mg, or 1,200 mg), valacyclovir 500 mg twice daily, or placebo.
Participants had to have at least 4 episodes of recurrent genital herpes in the last 12 months. If they received any sort of suppressive therapy within the last year, they had to have least one recurrence within stopping their suppressive therapy.
Patients, who received any dose of ASP2151, took the drug once a day for 3 days. Those who received valacyclovir took 500 mg twice a day for 3 days. Participants obtained swabs of their genital lesions within 6 hours of the first sign of recurrence. Then they initiated treatment and returned to the clinic within 24 hours of the first dose. The researchers did viral testing twice daily on days 2 and 6 and on days 8 and 10 if lesions were still present. Blood samples were drawn for pharmacokinetic analysis on days 1-4 and on day 17 (the end of the assessment period).
Patients were predominantly female (70%), with a mean age of 40 years. They typically had seven episodes per year. Half of the patients were only positive for HSV-2, while the other half were positive for HSV - 1 and HSV-2.
The primary endpoint for time to healing was significantly less for all active treatment groups, compared with placebo. Median healing times were 140 hours for placebo, 120 hours for ASP2151 100 mg, 106 hours for ASP2151 200 mg, 116 hours for ASP2151 400 mg, 102 hours for ASP2151 1,200 mg, and 114 hours for valacyclovir 500 mg.
The researchers calculated the hazard ratios for ASP2151 regimens and valacyclovir, compared with placebo: 1.40 for 100 mg of ASP2151, 1.40 for 200 mg of ASP2151, 1.25 for 400 mg of ASP2151, 1.72 for 1,200 mg of ASP2151, and 1.42 for valacyclovir. These results suggest similar efficacy for ASP2151 and valacyclovir, said Dr. Gordon.
In terms of duration of symptoms, all treatments were better than placebo, and ASP2151 regimens were comparable to valacyclovir. The most significant difference between placebo and all treatment regimens was duration of viral shedding. ASP2151 regimens were comparable to valacyclovir for viral shedding duration.
In ASP2151 treatment groups, the most common side effects were nausea, dizziness and headache. There were no severe adverse reactions.
The study was funded by Astellas Pharma. Dr. Gordon reported having no relevant disclosures.