By Randall Osborne
West Coast Editor
Just more than a week after stopping enrollment in a Phase III trial of its therapeutic vaccine Remune (HIV-1 Immunogen) to adjust the protocol, The Immune Response Corp. (IRC) said a Phase II study of the vaccine in Spain showed promising preliminary results against the AIDS virus.
Two-year data from the study, which is expected to last three years, were presented at the fifth European Conference on Experimental AIDS Research in Madrid, where attendees heard Remune - which IRC is developing with Agouron Pharmaceuticals Inc., of La Jolla, Calif., a wholly owned subsidiary of Warner-Lambert Co. - worked in a subset of patients.
IRC's stock (NASDAQ:IMNR) jumped more than 12 percent on the news, ending Wednesday at $9.937, up $1.25, after reaching a high of $11.
"It was a surprise to the market," said Kathy Lane, spokeswoman for Carlsbad, Calif.-based IRC. "Everyone who follows the company has known the trial was ongoing, but I don't think anybody was aware [IRC would] would present data at this conference."
All of the blood samples tested from a subset of people receiving antiviral drug therapy plus Remune showed significant killer, or CD8, T-cell activity specific to HIV. All those receiving the antiviral drug therapy plus placebo had little or no such response.
"[Researchers] decided they would closely monitor some participants, so they preselected three sites where they knew they could get the blood work done in an expeditious manner," Lane said.
"Memory" killer T cells, which are formed after exposure to a pathogen to bolster the organism for a quick defense when challenged by it again, also rose in the Remune group, as compared to the placebo group of the subset. Importantly, so did memory "helper" CD4 T cells.
Levels of the soluble cytokine interferon-gamma (by which the function of helper T cells can be measured) went up, too, in the Remune group as compared to the placebo group, both of which consisted of 27 patients.
Researchers told the Madrid conference that preliminary data suggest that getting the response of helper T cells and activation of T-cell precursors requires some consistent HIV exposure, as could be provided with a therapeutic vaccine such as Remune. Helper T-cell responses of Remune-treated patients may have kicked their killer T cells into gear, they said.
The Phase II study in Spain is a double-blind placebo-controlled trial at 13 sites, enrolling 243 HIV-infected patients who had not previously undergone antiviral drug therapy.
Scientists are measuring Remune's efficacy with antiviral therapy by comparing the time to increases in viral load, or decrease in CD4 helper T-cell counts, between the two groups: one given antiviral therapy plus Remune, and one given antiviral therapy plus a placebo.
Remune is an inactivated form of HIV, without the viral envelope, combined with a mineral oil-based adjuvant. It is injected every three months.
Earlier this month, IRC and Agouron said enrollment in a prospective 472-patient Phase III trial of Remune with highly active antiretroviral therapy in the U.S. was halted to reassess design of the protocol. At that point, 131 patients had been enrolled. (See BioWorld Today, June 12, 2000, p. 1.)
"Typically, the protocol changes are things like sample size and duration of the trial," Lane said. "If I had to guess, I'd say [it will be a change in] sample size. We don't want to do or say anything that would muddy the waters. The National Institutes of Health came to us, and it's footing the bill. All we're doing is supplying the Remune."
Last year, a Phase III trial of Remune was halted by an independent data safety monitoring board. The panel said the 2,500-patient, 120-week study could not meet its primary endpoint of reducing the rate of disease progression. (See BioWorld Today, May 18, 1999, p. 1.)
Remune has "had a rocky history," Lane acknowledged. "Part of it is being in the wrong place at the wrong time." For example, until Agouron became involved in development of the vaccine, the FDA would not accept viral load as a measure of its efficacy, she said.
The stock-price climb, Lane said, happened because the news about Remune was good, and because "it's a news-driven volatile stock, and you've got a market that's in love with biotech again."
An interim look at the Phase II data from the trial in Spain was scheduled for later this year, and more details from the trial are expected at a scientific conference next month.
Meanwhile, Alan Auerbach, vice president and research analyst with First Security Van Kasper in San Francisco, rates IRC stock as a "strong buy."
Auerbach said the market has undervalued IRC because "nobody's dug deep to see if something's there. If Remune has such a bad history, why is Warner-Lambert pumping so much money into it?"
Remune was "moving ahead long before the Spain results," he added.
In any case, Auerbach told BioWorld Today, there's more to the IRC story than Remune, which is one of a number of drugs in the pipeline - including a compound for rheumatoid arthritis, soon to enter Phase III trials, Auerbach said.
"It has double the market potential Remune's got, but no one realizes [IRC] has it," Auerbach said. "Just from the Vegas odds point of view, one of these is going to be a drug."