Next week, Hybridon Inc.'s antisense weapon against AIDS starts itsfirst human trial in the U.S.Following just-completed clinical studies in France of GEM 91, ananti-HIV, antisense molecule, a Phase IA human study gets under wayMay 19 at the University of Alabama.GEM, which stands for genetic expression modulation, is anoligodeoxynucleotide phosphorothioate, the first antisense compoundaimed at inhibiting HIV in humans. (See BioWorld, May 4,1993, p. 1.)The French Phase IA trial, at two of France's leading teachinghospitals, found the drug well-tolerated in 24 test subjects. Halfreceived it intravenously; half, subcutaneously. "There were no sideeffects," Hybridon's president and CEO, E. Andrews Grinstead III, toldBioWorld, "GEM appears to be clean." Hybridon is based inWorcester, Mass.Safety having been demonstrated in France, the Alabama GEM 91 willbe radio-labeled with isotopic sulfur (35S) as an imaging agent, inorder to observe the compound's distribution and pharmacokinetics inthe human body. Six HIV-positive but asymptomatic volunteers, withCD4 counts between 200 and 500, will receive a single dose of theoligonucleotide.The FDA, where GEM-91 has been awaiting an investigation new drugapproval for many months, has requested that Hybridon provide theFrench results, Grinstead recalled. "We filed it in March, together withsome monkey data they had asked for, and in less than 30 days wewere cleared" for the Phase IA Alabama study.The primate material FDA had requested, Grinstead said, "concerned acertain hypotension we had seen in monkeys. We were able todemonstrate the mechanism of action to the agency, showing the effectto be avoidable. "The FDA then asked that we provide that informationto other antisense companies, so we will publish it in a couple ofmonths.""Our intention," he said, "is to follow it immediately with a Phase IB/IIin late June."The University of Alabama at Birmingham is designated by theNational Institute of Allergy and Infectious Diseases as a Phase-Ifacility, because of its intensive drug-testing capabilities. The test willbe jointly coordinated by Robert Diasio, chairman of pharmacology,and Michael Saag of the university's AIDS clinic. Diasio said, "GEM91 represents a new therapeutic approach in the treatment of AIDS. Weare enthusiastic about the start of these trials." n
-- David N. Leff Science Editor
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