By Randall Osborne

West Coast Editor

After gaining momentum in April with positive data for its HIV drug Remune, The Immune Response Corp. took a hit Friday, when the company¿s shares lost 55.5 percent on news that a Phase II study in Spain failed to meet its primary endpoint.

IRC¿s stock (NASDAQ:IMNR) closed Friday at $2.18, down $2.72.

¿This jeopardizes not only the development of Remune, but the short-term future of the company,¿ said Alan Auerbach, an analyst with San Francisco-based Wells Fargo Van Kasper. ¿I wouldn¿t be surprised to see Pfizer pull out of the deal before the end of the year.¿

IRC is developing Remune with Agouron Pharmaceuticals Inc., of La Jolla, Calif., a subsidiary of New York-based Pfizer Inc. ¿They¿re conducting Phase III studies with Remune that are almost identical in design [to the failed Phase II study],¿ Auerbach said.

An independent data safety monitoring board evaluated results from IRC¿s Phase II trial of Remune (HIV-1 Immunogen), and found no significant difference between the treated group and the control group. Last year, IRC said preliminary results from the trial were promising. (See BioWorld Today, June 22, 2000.)

The primary endpoint was time to increase to 5,000 copies/ml of viral load (the amount of HIV detected in the blood) or a 50 percent decrease in CD4+ T cells/ml or a decrease to less than 250 CD4+ T cells/ml while on antiretroviral therapy.

But a subgroup of patients who were more immunocompetent seems to have shown a decrease in viral load, the board said, calling for more study. Eduardo Fernandez-Cruz, principal investigator in the study, said those patients represent the key to making Remune work.

¿If you are targeting the immune system of the patient, it¿s going to be important to evaluate a priori whether the immune system is competent or intact, capable of responding to this type of therapy,¿ he said. ¿We started the trial in 1997, and the protocol was written in 1996. At the time, there was no knowledge of what markers would establish ability to respond. Now, we know.¿

Other company officials were not available, but Fernandez-Cruz spoke from a hotel in New York, where they met with the safety board. He said markers will be used to select patients for a Phase III trial to get under way ¿in the next six months.¿

He told BioWorld Today ¿you will never be able to reach a primary endpoint in unselected populations. But, if we understand the concept behind the result we have shown, and understand the objective in the trial, no one in the world would say this has not been successful.¿

The study was conducted at 13 centers, and was a multicenter, double-blind, placebo-controlled, randomized trial of 243 antiviral-naive patients with chronic HIV infection with CD4+ T cells between 300-700 cells/ml. Viral load at entry ranged from less than 10,000 copies/ml to greater than 100,000 copies/ml. Results will be presented later this month at the Sixth European Conference on Experimental AIDS Research in Edinburgh, Scotland.

Remune has had a rocky history. In April, IRC¿s stock jumped 58 percent, closing at $2.58, on news of data showing that patients treated with Remune showed a reduction in viral load regardless of concomitant antiretroviral drug therapy. (See BioWorld Today, April 24, 2001.)

Auerbach, who downgraded IRC¿s stock to ¿underperform,¿ said the firm has neglected its pipeline. ¿It¿s extensive, but they have just not executed on development,¿ he told BioWorld Today. ¿This could be one of three drugs in Phase III testing.¿

IRC has IR501, a T-cell receptor peptide vaccine for rheumatoid arthritis, which has completed two Phase II trials, and IR502, a similar drug for psoriasis, also in development.

¿There¿s a million HIV-infected individuals in the U.S., and 2.5 million with rheumatoid arthritis,¿ Auerbach said. ¿And how about psoriasis? It¿s even higher.¿

Fernandez-Cruz, however, works only in the HIV program ¿ and he¿s determined to prove Remune¿s worth, in selected groups of patients and potentially larger segments.

¿Our studies have been consistent in showing patients that, conceptually, have competent immune systems will respond, regardless of viral load,¿ he said. Others won¿t respond, no matter what, he added.

¿The confusion [about results from the Phase II study] is in the minds even of the investigators and the evaluators, not in the data,¿ he said. ¿It¿s there. It¿s clear.¿

He recalled a conversation with vaccine pioneer Jonas Salk, who told him ¿there will be the ones who have the vision, understand the concept and are able to interpret what they see,¿ but many will not.

¿This is not an easy thing to do,¿ Fernandez-Cruz said. ¿But we¿ve come to a turning point, and from now on, we¿ll be in better shape. This is something that comes step by step. It¿s going to take some time.¿