As described in our recent feature, (Click here for access), the anti-infectives market is poised to experience considerable growth in the next few years, with a forecast market value that is expected to double in size to more than $44 billion by 2010. The treatment of the herpes simplex viruses, HSV1 and HSV2 has been targeted by a number of companies.

Health care professionals estimate between 20- 40% of the adult population (age 12 and over) experience recurrent facial cold sores (two or more per year) caused by HSV-1 infection. An estimated 50% of sufferers use OTC treatments spending hundreds of millions of dollars each year on such products that offer only limited benefits. A further 47% of individuals use home remedies or nothing at all. Only 1- 3% will seek doctor-prescribed agents.

Currently, no cure is available for HSV-1 infection. The development of Acyclovir (Zovirax), a potent, specific and tolerable nucleosidic inhibitor of the herpes DNA polymerase, was a milestone in the development of antiviral drugs in the late 1970s. This antiviral became the most prescribed treatment for herpes infection, taken orally 5 times daily for 5–10 days or applied topically 5 times daily for 5 days. Although acyclovir represents a trusted, safe and effective therapy for the treatment of herpes infections the need for multiple dosing means that the situation is far from optimal. Furthermore treatment reduces cold sore healing times by only 10-15%, or 12-24 hours. When acyclovir became a generic drug in the mid-1990s, valacyclovir (Valtrex) and famciclovir (Famvir) were launched.

In 2002, both Bayer and Boehringer-Ingelheim researchers reported new thiazolylphenyl inhibitors of HSV helicase-primase. BAY 57-1293, an inhibitor of this enzyme, was shown to possess potent in vitro anti-herpes activity, was well-tolerated, significantly reduce time to healing, prevent rebound of disease after cessation of treatment and, most importantly, reduce frequency and severity of recurrent disease. Likewise, BILS 179 BS was also reported as an orally active antiviral in murine models of HSV-1 and HSV-2 disease and more effective than acyclovir when the treatment frequency was reduced or when initiation of treatment was delayed up to 65 hours after infection. These studies validated the use of helicase-primase inhibitors for the treatment of acute herpes virus infections.

Most recently Boehringer-Ingelheim researchers have published data describing BILS 45 BS, another helicase-primase inhibitor which is more potent than acyclovir against wild-type clinical and laboratory HSV-1 strains and also acyclovir-resistant HSV isolates. Following cutaneous infection of nude mice, acyclovir-resistant strains of HSV-1 induced significant, reproducible, and persistent cutaneous lesions that lasted for more than 2 weeks. Oral treatment with acyclovir not surprisingly failed to affect infection. In contrast, BILS 45 BS at an oral dose of 100 mg/kg/day almost completely abolished cutaneous lesions mediated by these strains. The 50% effective dose of BILS 45 BS was approximately 50 mg/kg/day. These data support the potential use of HSV helicase-primase inhibitors for the treatment of both nucleoside-sensitive and resistant HSV disease in humans.

Entry date Monday, June 30, 2003

Adapted from Duan et al, Antimicrob Agents Chemother. 2003 Jun;47(6):1798-804.

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