SMITHKLINE BEECHAM PRODRUG FAMCICLOVIR FOR VARICELLA ZOSTER
SMITHKLINE BEECHAM PRODRUG FAMCICLOVIR FOR VARICELLA ZOSTER has a "principle advantage" over Burroughs Wellcome's Zovirax (acyclovir) in that it can be given three times a day instead of five times a day, and is "at least as effective as acyclovir," John Gnann, MD, University of Alabama at Birmingham, told a scientific workshop on varicella zoster virus infection May 14 in Bethesda, Md. The meeting was cosponsored by the VZV Research Foundation and the National Institutes of Health. Gnann discussed results of a study conducted in Europe and Canada testing famciclovir in 544 immunocompetent patients with varicella zoster. Patients were divided into four treatment groups and given either 800 mg acyclovir five times daily, 250 mg famciclovir three times daily, 500 mg famciclovir three times daily, or 750 mg famciclovir three times daily. A preliminary study analysis found "no significant differences in rates of cutaneous healing, no significant difference in loss of pain and that the safety and tolerance of famciclovir among any of the four [treatment] groups was the same" as acyclovir, he noted. Gnann described famciclovir as being "readily orally absorbed." SmithKline has said famciclovir (BRL-42810) is in Phase II. Industry interest in more patient-friendly shingles treatments appears to have picked up, in part due to the growing geriatric population and the recent addition of a chicken pox indication for Zovirax. The varicella virus causes shingles or chickenpox in about 90% of the population. An estimated one in five people will develop shingles during a 75-year lifetime, with the incidence and severity increasing with age and lowered immunity. BVaraU, developed by Bristol-Myers Squibb, also has shown antiviral activity against varicella zoster, Gnann said. In vitro, BVaraU's activity against shingles is "1,000-fold higher than acyclovir," Gnann stated. The current clinical trial dosage of BVaraU is 40 mg once a day. The major potential problem with the drug is that it has been found to be carcinogenic in rodent studies, Gnann maintained, causing increased incidence of liver and testicular tumors at high doses for long duration. Burroughs Wellcome is testing two other drugs, the Zovirax prodrug valaciclovir and 882C87, for use against varicella zoster. According to Gnann, 882C87 is "five to seven-fold more active" in vitro against varicella zoster than acyclovir, has a "very prolonged" half-life of 12 to 14 hours, and could be given in 100 to 200 mg doses once- or twice-daily. Burroughs-Wellcome expects to file an NDA for valaciclovir in 1994 for treatment of herpes simplex and varicella zoster ("The Pink Sheet" May 10, p. 13). The compound has the same safety profile as acyclovir at a two-to- three times daily dose. Wellcome also has another compound in preclinicals, 6- methoxypurine arabinoside, an ara-M derivative, Gnann said. Other companies conducting preclinical testing for antivirals for varicella zoster include Abbott with A, 79296 and A, 73209, and SmithKline Beecham with mappicine ketone.
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