By Mary Welch

Despite having its Phase III trial with Remune cut short because endpoints no longer were attainable, The Immune Response Corp. presented data showing Remune exhibited a significant increase in lymphocyte proliferation that is associated with a decrease in viral load.

"This data seems to support the premise that Remune may lead to the control of the HIV infection," said Dennis Carlo, president and CEO of the Carlsbad, Calif., company. "This result helps prolongs disease progression in the body. The lower the viral load, the more favorable the prognosis."

The results were presented at the Royal College of Physicians in London and were based on a recently concluded 120-week study with 2,500 HIV-infected people. Patients were allowed to follow any regimen of antiviral therapy and switch antiviral drugs as needed. In a random, preselected subset of 252 patients who took the immune-based therapy, Remune, plus the drugs or the drugs and placebo, it was shown that lymphocyte proliferation was significantly higher in individuals who received Remune than with those who didn't.

Typically, patients with HIV don't show a lymphocyte proliferative response because their immune systems are impaired and therefore can't fight the infection. However, following treatment with Remune, the lymphocyte proliferative responses seem to have been restored in some patients, Carlo said. This observed HIV-specific lymphocyte proliferation was associated with control of the virus in the patients' plasma.

"In addition, there was a significant increase in CD4 cells in the patients treated with Remune," he said.

Remune is an inactivated form of HIV lacking its envelope that is combined with a mineral oil-based adjuvant. The drug, which is injected every three months, is designed to stimulate a patient's own immune defenses to keep the virus in check.

When the company started its Phase III trial of Remune back in 1996, the rate of disease progression for HIV-infected patients was 6 percent; now with new drugs, that rate is less than 1 percent.

"When we started the study, the FDA didn't recognize surrogate endpoints such as showing a reduction in viral load as a means of showing efficacy," he said. "Now they do. This study is important because it shows that patients on the drugs who also take Remune experience a statistically significant reduction in viral load vs. those patients on a placebo."

Because it was operating under the more difficult endpoint of reducing the rate of disease progression, an independent data safety monitoring board suggested the 2,500-patient, 120-week trial be stopped because endpoints could not be met. (See BioWorld Today, May 18, 1999, p. 1.)

The company, along with partner Agouron Pharmaceuticals Inc., of La Jolla, Calif., started a pivotal trial of Remune in combination with highly active antiretroviral therapy (HAART) to treat HIV infection. In the trial, researchers hope to determine whether the addition of Remune to a HAART regimen of Viracept and Combivir delays the time to virologic failure. Some 700 patients will be involved in the trial that will last at least 48 weeks. (See BioWorld Today, Sept. 28, 1999, p. 1.)

The two companies agreed to jointly develop Remune in a deal worth up to $77 million to Immune Response. (See BioWorld Today, June 12, 1998, p. 1.)

In addition, an independent safety monitory board recommended the Remune trial in Spain be taken to its conclusion. The decision followed a review of efficacy data from the trial concerning viral load and CD4 helper T-cell counts.

Carlo was encouraged by the decision. "We believe that while antiviral drugs interrupt the reproduction process of HIV within infected cells, Remune may stimulate the immune system to destroy HIV-infected cells, an ability that is lost soon after infection with HIV."

The study in Spain is a double-blind placebo-controlled trial that has enrolled 242 HIV-infected patients not taking antiretroviral drugs (ARTs). The efficacy will be assessed by comparing the time to increases in viral load and decreases in CD4 helper T-cell counts between patient groups that received ART plus Remune or ART plus placebo.

Also being monitored are several immunological markers of HIV disease progression such as T-cell proliferation, chemokine and cytokine production and cytotoxic T cells. The trial should end in the second half of 2000.

The Immune Response Corp.'s stock (IMNR) closed Thursday at $4.312, up 37.5 cents.