Tuesday, Jun 6, 1989
Montreal -- June 6, 1989 --Genentech, Inc. today announced plans for three new sets of clinical trials to begin between now and the end of the year for its recombinant CD4 drugs, which are being tested as potential treatments for acquired immune deficiency syndrome. The announcement follows presentations by Genentech's clinical investigators on soluble recombinant CD4 Phase I safety and dosage studies delivered here today at the Fifth International Conference on AIDS.
"Although we have established recombinant CD4 is safe, it is too early to draw any conclusions about its effectiveness in treating AIDS," said Stephen A. Sherwin, M.D., vice president of clinical research. "The initial results reported in Montreal make it clear we must take immediate steps for a timely yet thorough investigation of the potential of CD4 to help those suffering from this horrible disease," he said. "Genentech is making a strong commitment to expand our work to determine as rapidly as possible if the early promise of CD4 can be realized."
The results presented at the AIDS conference by Genentech's investigators are for Phase I studies begun last August, the first to test soluble recombinant CD4 in humans. Last February, Genentech scientists published a paper on new development with CD4, the invention of a novel hybrid molecule. The hybrid molecule is now undergoing animal testing and Genentech is currently working toward entering this second and unique potential new CD4 drug into human clinical trials before the end of this year.
The hybrid molecule is constructed by genetically combining a portion of CD4 and a portion of a human antibody molecule. Termed an "immunoadhesin," this molecule may itself act like a human antibody and stimulate the body's own immune system to attack the AIDS virus directly. This antibody activity is only a theory and must be tested in animal and human studies. Animal studies already conducted show that the hybrid molecule may improve recombinant CD4 by increasing its half-life, which could dramatically improve its therapeutic effect.
"Our Phase I results with soluble recombinant CD4 indicate the potential higher half-life of the hybrid molecule may prove to be important in establishing efficacy," Sherwin said. "Although we are still in very early stages of development, we are working as quickly as possible to test the potential added benefits of the hybrid molecule as well as significantly expanding our studies of soluble recombinant CD4."
Phase II/III studies of the original soluble recombinant CD4 are being organized now under the auspices of the National Institute of Allergies and Infectious Disease (NIAID) at the National Institutes of Health (NIH). Clifford Lane, M.D., associate director of NIAID, is the principal investigator who is currently enlisting collaborating centers throughout the United States. The Phase II/III studies are part of the U.S. Food and Drug Administration's new guidelines to accelerate testing of drugs which are potential treatments for AIDS and other fatal diseases.
The randomized two-year study will involve 600 patients and be designed to test the efficacy of soluble recombinant CD4. Patients will be treated with soluble recombinant CD4 alone, AZT alone or a combination of soluble recombinant CD4 and AZT. The Phase II/III clinical trials are anticipated to begin this fall.
Two pediatric Phase I studies of soluble recombinant CD4, the first to test CD4 in infants and children, are beginning this month. Patients are currently being screened for enrollment in three-month safety and dose-ranging studies scheduled to conclude this September.
One study, with Phillip Pizzo, M.D., of the National Cancer Institute (NCI) at NIH as principal investigator, will use continuous infusion and involve 26 children aged from birth to 13 years-old. Collaborating centers are Walter Reed Army Hospital, Washington, D.C., the University of Maryland, and Children's Hospital, Washington, D.C.
The second pediatric study, with Peggy Weintrub, M.D., University of California at San Francisco as principal investigator, will use bolus injection and involve 24 patients aged from birth to 18-years-old. Collaborating centers are Children's Hospital, Newark, N.J., Stanford University Medical Center, Palo Alto, Calif., Duke University Medical Center, and Children's Memorial Hospital, Chicago.
The Phase I clinical trials begun last August and reported today in Montreal have been extended and are continuing as Phase I/II studies to gather long-term safety data and to compile efficacy data. Some of the 48 patients in this study are already taking soluble recombinant CD4 in combination with AZT. These clinical trials are being conducted at San Francisco General Hospital, New England Deaconess Hospital, Boston, and the NCI. Principal investigators are Paul Volberding, M.D., San Francisco General Hospital and Samuel Broder, M.D., NCI director.
In the test tube, it has been shown that recombinant soluble CD4 acts like a decoy, or molecular sponge, entrapping the virus. In theory, CD4 may be able to stop the progression of AIDS by blocking the HIV virus from infecting healthy cells and binding the potentially detrimental parts of the virus envelope. Genentech cautions that work involving recombinant CD4 is still in early investigational stages and must be proven in extensive human clinical trials.
Genentech, Inc., is a biotechnology company focusing on the development, manufacture and marketing of pharmaceutical products produced by recombinant DNA technology.Editor's Note:
Two news releases on the CD4 Phase I results reported in Montreal were issued. One by the University of California at San Francisco with New England Deaconess Hospital and the other by the National Cancer Institute.
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