San Diego Business Journal

While advances using a mix of drugs have helped keep HIV infection in check, many researchers remain skeptical about the prospects of ever killing the deadly virus and a breakthrough has yet to be made in the $5 billion market for AIDS therapies.

Two San Diego-based biotechnology firms hope to be on the forefront in the fight against HIV.

Both Immune Response Corp. and Hollis-Eden Pharmaceuticals Inc. are developing vaccines with one major goal: to restore HIV-infected patients' damaged immune systems. If proven successful, they would be milestones in the currently uncertain world of AIDS research.

Both start-ups presented encouraging data from a small number of patients at last week's 13th International AIDS Conference in Durban, South Africa.

The two biotechs each showed in two small patient studies that HIV-damaged immune systems got a boost from the respective vaccines.

Scientists say it remains to be seen whether therapeutic vaccines can boost the immune system enough to control HIV infection.

Still, the promise of anti-AIDS vaccines is so intriguing that it is now the fastest growing and hottest area of research.

Few scientists believe the drugs presently used are enough.

Dr. Ron Moss, vice president of medical and scientific affairs at Immune Response agrees.

"It's a scary time even though there are some effective therapies out there," said Moss, pointing to recent reports of a 60 percent increase in new HIV-infections in San Francisco last year as a result of risky sexual behavior.

Scientists no longer believe hitting HIV as soon and as hard as possible after infection is an adequate course of treatment, he said.

Drug "cocktails" made up of protease inhibitors and retroviral therapies prolong patients' lives, but don't kill the virus, and they have been shown to fail in 30 percent of all patients, he added.

Patients taking these costly drug cocktails need to adhere to a strict medication regimen, often taking some 25 pills a day, and often suffering toxic side effects.

Using vaccines in an attempt to prevent initial infection haven't been successful, but Immune Response and Hollis-Eden hope providing vaccination after infection will prove successful.

Both vaccines, Immune Response's Remune and Hollis-Eden's HE2000, are being tested in the U.S. and Europe on HIV-positive patients combined with antiviral therapies.

The aim is to keep the virus in check with the drug cocktails while stimulating the body's immune response using vaccine therapy.

In developing countries where patients can't afford the costly drug cocktail therapy, both vaccines are being tested as stand-alone therapies.

Moss said researchers hope the vaccines will delay patients' need for further drug treatment and the onset of AIDS.

In Durban, Immune Response presented new data on Remune from two clinical trials.

In one follow-up study where 27 patients in Thailand received a single injection of Remune every three months for 136 weeks, patients showed an increase of 100 CD4 T-cells , a key immune-system cell affected by HIV , and no increase of HIV in the blood on average, Immune reported.

A smaller study in Spain showed Remune added to an antiviral drug cocktail helped increase the number of killer T-cells that fight HIV, Moss said. Details were not available.

Experts agree, it will take a much larger study to determine whether the increased number of T-cells can wipe out HIV.

Moss hopes to use additional data from the Spain study to file for drug approval with the Food and Drug Administration by the first quarter of 2001. The firm has teamed up with San Diego's Agouron Pharmaceuticals Inc., a unit of Warner-Lambert Co., to market the drug.

By contrast, Hollis-Eden plans to develop HE2000 alone to maximize shareholder value, said Richard Hollis, chief executive officer at Hollis-Eden.

He said the firm has raised enough money to finance drug development on its own. Hollis-Eden has raised $70 million since 1997 and has $45 million in the bank.

In Durban, Hollis presented data from 37 patients injected with HE2000 for five consecutive days in a Phase I/II study in South Africa.

Results showed significant increases in CD8 T-cells which kill virally infected cells, and a boost in the immune systems of patients.

Hollis said immunologists have identified two major branches of the immune system, called Th1 and Th2.

The Th1 branch promotes a strong immune response against pathogens that reside inside cells, such as HIV. The Th2 branch promotes production of antibodies against pathogens that reside outside the cell, such as bacteria.

HIV-infected patients go for years without developing AIDS because they have developed higher levels of Th1 anti-viral protection. If a person's immune system shifts to a Th2 antibacterial mode, it becomes ineffective against fighting HIV.

Hollis believes shifting a dysregulated immune system with a Th2 bias back to Th1 could be an effective therapeutic therapy.

He hopes to show that HE2000 can boost the immune system and fight the virus, and prevent opportunistic diseases and the onset of AIDS.

As with Remune, it's too early to say if HE2000 will be successful, experts say.

Additional tests in Africa are on the way, Hollis said. In the United States, HE2000 will be tested on patients who failed antiviral drug therapies, he said.

Meanwhile, the HIV epidemic continues to rise at an alarming rate.

According to the Center for Disease Control and Prevention an estimated 16,000 Americans died from AIDS last year as a result of HIV-infection. More than 5 million Americans are at risk to contract the virus as a result of risky behavior, according to new studies released in Durban.

Therapeutic vaccines could be less costly, because they are easier to make and administered less often, Moss said.