ARIAD Demonstrates Method For Orally Activated Protein Therapy
December 2, 1997 09:45 AM
CAMBRIDGE, Mass., Dec. 2 /PRNewswire/ -- ARIAD Pharmaceuticals, Inc. ARIA today published a study demonstrating that precisely controlled doses of therapeutic proteins can be delivered in vivo in response to the administration of an orally active drug. The study shows that it may be possible to overcome current limitations of protein therapy, which include the requirement for delivery by injection and the difficulty of maintaining stable and therapeutically relevant levels of protein in the patient.
ARIAD's method for orally activated therapeutic protein production, called ARGENT(TM) (ARIAD Regulated Gene Expression Technology), is expected to enter human clinical trials next year. Initially, ARIAD plans to apply ARGENT(TM) in large therapeutic protein markets, such as those for growth hormone (adult pituitary dysfunction, muscle wasting), erythropoietin (anemia) and alpha interferon (hepatitis C). Therapeutic proteins currently account for over $11 billion in worldwide sales.
The ARGENT(TM) therapeutic protein delivery system is based on transcription factors, intracellular signaling molecules that activate gene expression. ARIAD has engineered proprietary transcription factors that activate expression of a target gene only when they interact with a specific small-molecule drug. As a result, cells equipped with ARGENT(TM) and a therapeutic gene do not produce therapeutic protein in the absence of the activating drug. However, when the drug is administered, it activates the transcription factor, the target gene is expressed, and therapeutic protein production is turned on.
In the ARIAD study, published in the December 1997 issue of the Journal of Clinical Investigation, ARIAD scientists placed engineered cells in the muscle tissue of mice. These cells contained ARGENT(TM) as well as an engineered gene for human growth hormone (hGH). In the absence of drug, these mice produced no circulating hGH. However, when the drug was administered orally, hGH was produced. The amount of hGH circulating in the mice correlated closely with the dose of drug they received.
Measurable amounts of hGH could be detected in the mice eight days following a single oral administration of the activating drug. These prolonged circulating levels of hGH were encouraging. Because the half life of hGH in mice is only a few minutes, conventionally delivered hGH is cleared from the circulation rapidly. However, since the engineered cells produced hGH continuously in response to the circulating drug, it was possible to achieve stable, long-lasting and therapeutically relevant levels of hGH in the mice with a single dose of activating drug.
"By converting injectable protein therapy into oral drug therapy, we intend to achieve several improvements," said Michael Gilman, Ph.D., ARIAD's chief scientific officer. "In addition to making protein therapy more convenient for the patient, it may be possible to improve the safety and efficacy of therapy by maintaining and controlling the dose of therapeutic protein within an optimal therapeutic window."
In addition to preclinical testing of ARGENT(TM) in mice, ARIAD and its collaborators are conducting studies in primates. At the same time, ARIAD is scaling up production of the ARGENT(TM) activating drug in preparation for human clinical trials, which are planned to commence within the next year.
ARIAD Pharmaceuticals is a leader in the discovery and development of orally administered therapeutics based on signal transduction technology. ARIAD's integrated drug discovery platform includes extensive efforts in functional genomics research, small-molecule drug design and regulated gene therapy.
Some of the matters discussed in this news release are forward-looking statements that involve risks and uncertainties, including but not limited to risks and uncertainties regarding the success of the Company's preclinical studies, the ability of the Company to commence clinical trials and the success of such clinical trials, as well as economic, competitive, governmental and technological factors affecting ARIAD's operations, markets, products, services and prices, and other factors discussed under the heading "Cautionary Statement Regarding Forward-Looking Statements" in ARIAD's Annual Report on Form 10-K filed with the Securities and Exchange Commission. SOURCE ARIAD Pharmaceuticals, Inc. |
