SBIR-STTR Award

n-Docosanol is a 22-carbon primary alcohol that can inhibit herpes simplex virus (HSV) replication in tissue culture and cutaneous HSV disease in guinea pigs. Recent clinical trials documented that a cream formulation of n-docosanol is safe and effective for the treatment of herpes labialis in humans, and a New Drug application has been submitted to the Food and Drug Administration for marketing approval for the indication. The guanosine analog acyclovir remains a leading approved drug for the treatment of oral and genital HSV diseases. Clinical data indicate that antiviral therapy for such diseases can still be substantially improved over what is observed with acyclovir or n-docosanol monotherapy. Combination therapy using drugs with disparate mechanisms of action has proven to be highly effective for the treatment of viral diseases. Combination therapy with n-docosanol plus acyclovir would be reasonable because a) they have distinctly different mechanisms of action for inhibition of HSV replication, b) both exhibit favorable toxicity profiles, and c) it was recently observed that n-docosanol can synergistically enhance the anti-HSV activity of acyclovir in tissue culture. The purpose of this proposed research is to corroborate these tissue culture results using a cutaneous HSV model in guinea pigs. Skin on the backs of guinea pigs will be inoculated with HSV. The skin sites will be treated with n-docosanol and acyclovir, alone or in combination. If combination therapy using n-docosanol plus acyclovir proves to be substantially better than either drug alone in the model, feasibility would be indicated for this strategy in the treatment of primary and recurrent mucocutaneous HSV disease in humans. PROPOSED COMMERCIAL APPLICATION: Less than 1 in 5 US patients with recurrent HSV disease seek treatment, in part, because presently approved drugs limit the disease from a duration of approximately 6 days to approximately 5 days. If a combination of n- docosanol plus acyclovir can be shown to have clear benefits over either drug alone, a substantial marketing advantage would be indicated. This is particularly true if an effective combination can be delivered as a topical formulation, emphasis of this research

There is a substantial need for a safe, effective topical treatment for genital herpes simplex (HSV) disease. The proposed research aims to evaluate feasibility of continued development of docosanol as a topical treatment for recurrent genital herpes simplex infections. In order to achieve this objective, we have developed the following specific aims: Aim 1: Develop a new formulation optimized for application to genital areas. Aim 2: Establish efficacy of the new formulation in an animal model of genital herpes. Aim 3: Test selected formulation for safety and tolerability in toxicology studies that meet FDA requirements. Phase II will expand on the Phase I outcome which showed that formulations containing both docosanol and acyclovir provided maximal inhibition of HSV disease in a cutaneous guinea pig model when compared to formulations containing either docosanol or acyclovir alone. Upon successful completion of the aims and establishment of safety and efficacy in the nonclinical models, the applicant intends to initiate Phase 2 and 3 clinical studies of the efficacy of topical docosanol formulations in the treatment of recurrent episodes of genital herpes. If proven safe and effective, it would provide a new single agent treatment as well as allow concurrent use with acyclovir. PROPOSED COMMERCIAL APPLICATION: Topical treatment for recurrent genital herpes infections.

Thesaurus Terms:
Alphaherpesvirinae, Herpes simplex disease, acyclovir, alcohol, antiviral agent, combination chemotherapy, dosage forms, drug design /synthesis /production, drug screening /evaluation nonhuman therapy evaluation, topical drug application guinea pig