Immune Response Corp. is expected to launch a Phase III U.S. studyin mid-March 1996 of its HIV therapeutic vaccine _ the first suchAIDS treatment to reach late-stage testing _ to determine if thetherapy can stabilize progression of the deadly disease.
The HIV-1 immunogen, called Remune, is Immune Response's leadproduct and has been in clinical development since 1987.
If the immune system stimulating treatment demonstrates success inthe upcoming three-year study, officials of the Carlsbad, Calif.-basedImmune Response expect the therapy to be used in association withantiviral drugs, such as nucleoside analogs and protease inhibitors,which interrupt viral replication.
While the antiviral drugs target HIV-infected cells, ImmuneResponse's therapeutic vaccine is designed to rally the immunesystem's own killer T cells and antibodies to fight the reservoir ofvirus and stop HIV from infecting new cells.
Richard Trauger, senior scientific officer for Immune Response, saidRemune is inactivated HIV combined with a mineral oil-basedadjuvant to help boost the immune system's response to the virus'proteins.
Through purification, the inactivated HIV loses the glycoprotein (gp)120, which is an envelope protein that helps the virus infect cells.Immune Response officials said loss of gp120 is a benefit, allowingRemune to stimulate an immune response independent of the quicklymutating surface protein, whose changes assist the virus in avoidingattack.
Genentech Inc., of South San Francisco, and Chiron Corp., ofEmeryville, Calif., have developed preventive vaccines based ongp120. After Phase I and Phase II studies, the National Institutes ofHealth in 1994 declined to support continued development saying thedata were not promising enough for large scale studies.
Chiron has been working with Pasteur Merieux Connaught, ofSwitfwater, Pa., on methods of improving the gp120 vaccine andGenentech last week said it was starting a new company to revivedevelopment of its version. (See BioWorld Today, Feb. 15, 1996, p.1.)
Remune is not a preventive vaccine, said Charles Cashion, ImmuneResponse's chief financial officer. The goal is to begin using Remuneas HIV is detected, when a patient's immune system begins to fightthe virus. The therapeutic vaccine, in theory, would enhance theantibody and killer T cell assault.
In the Phase III trials, enrollment will be limited to AIDS patientswith CD4 counts of between 300 and 550. However, if Remune wereapproved for marketing, Cashion said it would be targeted fortreatment at earlier stages of the disease when CD counts are higher.A healthy person has CD4 counts of more than 1,000.
Cashion said 3,000 AIDS patients will be enrolled in the study. Aninterim analysis will be made one year after the start of the trial,which will be conducted at 50 medical centers throughout the U.S.The primary endpoint for the study is clinical, preventing patientsfrom progressing to opportunistic infections or death. Data also willbe collected on surrogate markers _ increasing CD4 counts anddecreasing viral load _ for research purposes.
Patients in the study will receive Remune plus the adjuvant onceevery three months in addition to any antiviral drugs they are taking.The placebo control group will receive the adjuvant and a placebo.
In addition to the Phase III U.S. trial, Immune Response will beginclinical studies in Thailand this year under a collaboration withBangkok-based Trinity Medical Group Ltd. A Phase III study therewould not get under way until 1997.
Immune Response's path to late-stage clinical trials with Remune hasnot been smooth. The company lost its corporate partner, Rhone-Poulenc Rorer, of Collegeville, Pa., a year ago. The two formed ajoint venture in 1988 to develop the HIV-1 immunogen, which wasfirst proposed by Jonas Salk in 1987.
Immune Response and Rorer battled over control of development andthe latter withdrew from the project in March 1995, giving the formerfull rights to the therapy.
The immunogen's development progress also suffered after membersof the FDA's Vaccines and Related Biologicals Advisory Committeein 1995 expressed reservations about the potential effectiveness ofthe treatment based on Phase II/III trial data from 1993. Remune wasjudged safe.
Despite the concerns, the advisory committee in January 1995recommended the FDA approve a Phase III trial. Last week, the FDAapproved the manufacturing facility in King of Prussia, Pa., andTuesday the agency cleared the way for the Phase III trial to begin. n
-- Charles Craig
(c) 1997 American Health Consultants. All rights reserved.