An Aids Drug With A New M.O.?

It may kill the fuel the virus uses to spread--in animals

Experts in AIDS research rarely get excited at the first report of a new drug. After all, few test-tube successes are repeated in animal experiments. Indeed, David M. Anderson, assistant director of the Washington Regional Primate Center at the University of Washington in Seattle, is so used to seeing ambiguous data from animal tests that he was surprised when he saw data on a new drug called HE2000. Infected monkeys taking the drug "lived longer, gained weight, and had more energy," he says. "It was not an outcome I expected."

Now the expectations for HE2000 are rising. If it proves effective in humans, it could be a breakthrough in the $5 billion market for AIDS therapies. On May 6, HE2000's maker, San diego-based Hollis-Eden Pharmaceuticals Inc. launched a clinical trial in humans in South Africa, and one week later won approval from the Food & Drug Administration to begin clinical trials in the U.S.

GREAT NEED. It's far too soon to say whether HE2000 could really be an effective AIDS drug. And Hollis-Eden is so tiny most Wall Street biotech analysts barely notice it. But the drug's success in animal trials suggests Hollis-Eden may be on to something important. "It's an interesting drug," says P. Spencer Cox, a director at Treatment Action Group, an AIDS advocacy organization. "But we don't know anything about its safety or efficacy."

There is a desperate need for new types of AIDS drugs. At least 33 million adults and children worldwide are now living with HIV, the virus that causes AIDS, according to UNAIDS, the United Nations program on HIV/AIDS. Drug cocktails made up of protease inhibitors and retrovirals can keep HIV in check and stave off full-blown AIDS. But they cost thousands of dollars a year, and don't eradicate the virus. With prolonged use, the virus may also become resistant to the drugs. Recent studies show that up to 28% of people being infected with HIV today get viral strains resistant to at least one AIDS drug.

HE2000 could prove to be cheaper than the cocktails because it's easier to make and it's administered less often. HE2000 might also address the resistance problem. The drug is a synthetic version of DHEA, a naturally occurring hormone. Unlike the currently prescribed drugs, HE2000 appears to work by shutting down key cellular proteins the virus needs during infection. "That's important," says Dr. Thomas C. Merigan, the director of Stanford University's Center for AIDS research. "If something works on the cell, not the virus, there is less pressure for the virus to mutate and become resistant." Says Richard B. Hollis, "We want to look at HIV and other diseases from a different perspective in the hopes of developing breakthrough compounds."

DUBIOUS. So far, the data from Anderson's study on monkeys are promising. Three that had been infected with an extremely virulent virus were given two courses of the drug over three months. None became resistant to the treatment or experienced side effects, and all lived nearly twice as long as the animals in the control group. Still, even though the monkeys' viral levels fell 95%, detectable levels remained, indicating HE2000 didn't completely wipe out the virus. "We have seen a beneficial effect, but we need to do more research," says Anderson.

Some AIDS activists are dubious. Martin Delaney, founding director of Project Inform, worries that HE2000 could be another drug with an ill-defined mechanism that doesn't work. "I'm very skeptical," he says. Other researchers warn that many promising treatments disappoint in human tests. "We still need to see a successful proof of concept in people," says Dr. Jacob P. Lalezari, a virologist at the University of California at San Francisco.

That's why the human trials are critical. Hollis-Eden hopes for results from its U.S. and South Africa tests by September. If the outcomes are positive, HE2000 and Hollis-Eden could be on the fast track to larger successes.