By Lisa Seachrist

Washington Editor

The Immune Response Corp. and Agouron Pharmaceuticals Inc. have started a Phase III study testing whether the addition of their therapeutic vaccine, Remune (HIV-1 immunogen), to highly active antiretroviral therapy (HAART) can prolong the durability of these therapies.

The trial is being conducted through the Adult AIDS Clinical Trial Group, a multicenter cooperative clinical trials group funded by the Division of AIDS in the National Institute of Allergy and Infectious Disease. The companies are supplying Remune and funding the laboratory tests as well as other aspects of the study.

The trial is the second Phase III study of Remune announced by Carlsbad, Calif.-based Immune Response (IRC) and La Jolla, Calif.-based Agouron in the past year, since a previous Phase III study was cut short for failure to meet its endpoints. In this study, the companies will test whether Remune added to a stable regimen of HAART can prolong the effectiveness of a specific combination of HAART drugs.

"We're looking at whether we can prolong the durability of HAART with Remune on board," said Joy Schmitt, spokeswoman for Agouron, a wholly owned subsidiary of the Warner-Lambert Co., of Morris Plains, N.J. "That's why we are looking at patients who are already having success with HAART."

The clinical study will look at patients who are on a stable regimen of HAART that has brought levels of HIV-1 RNA in the blood down to less than 500 copies per milliliter and have CD4 T-cell counts greater or equal to 300 cells per cubic milliliter. The study permits all combinations of HAART.

"The important thing about Remune is that we believe it works better in patients with suppressed viral loads as compared to high viral loads," Schmitt said. "That's why we are looking at these patients."

Half of the 472 patients enrolled in the study will receive an injection of Remune once every three months, while the other half will receive an injection of mineral oil-based adjuvant in addition to the HAART therapy. The study will run for 96 weeks and will assess the time to virologic relapse (a predetermined level of HIV-1 RNA detected in the blood). The company has planned for an interim analysis of data at 48 weeks to assess any differences between the Remune-treated group and the control group.

Remune is an inactivated form of HIV lacking its envelope. It is combined with a mineral oil-based adjuvant and is designed to stimulate a patient's own immune defenses to keep the virus in check.

When IRC began development of Remune in 1996, the company designed a large pivotal trial of 2,500 patients to test whether the therapy could slow the progression to AIDS. In the meantime, HAART became the standard of care, and the rate at which HIV-infected patients see their disease progress to AIDS has plummeted. In 1999, the company shelved the study on the advice of a data safety monitoring board because too few patients progressed to a diagnosis of AIDS. (See BioWorld Today, May 18, 1999, p. 1.)

In September, IRC and Agouron announced a Phase III study of Remune in HIV-infected patients who had never been treated. The study is testing the time to virologic relapse in patients receiving the combination of Viracept and Combivir with and without the addition of Remune. The study disclosed Wednesday expands Remune's role into treatment-experienced patients. (See BioWorld Today, Nov. 5, 1999, p. 1.)

Agouron signed a $77 million pact with IRC to develop Remune six months before being acquired by Warner-Lambert in a $2.1 billion deal. (See BioWorld Today, Jan. 27, 1999, p. 1; and June 12, 1998, p. 1.)

IRC's stock (NASDAQ:IMNR) closed Wednesday at $8, down 79.68 cents.