Dec. 18, 2000--Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN - news) announced that it has initiated a Phase I clinical trial to assess the safety and tolerability of the Company's interleukin-1 (IL-1) Cytokine Trap in patients with rheumatoid arthritis.
The placebo controlled, double blind, dose-escalation study will be conducted at several centers in the United States and includes a single dose phase and a multiple dose phase.
``The IL-1 Trap clinical trial is an important milestone for Regeneron,'' commented Leonard S. Schleifer, M.D., Ph.D., President and Chief Executive Officer of Regeneron. ``The IL-1 Trap is the first of a series of drug candidates that is based on Regeneron's basic insights into how cytokines work and our proprietary Trap technology. The IL-1 Trap clearly demonstrates how Regeneron's molecular and biological expertise, combined with our process science, protein manufacturing, and preclinical development capabilities, can lead to potentially important drug candidates. Over the next year, we also expect to initiate clinical trials of a Vascular Endothelial Growth Factor (VEGF) Trap to block angiogenesis and vascular permeability in settings of cancer and other conditions and a dual Trap for both interleukin-4 and interleukin-13 for asthma/allergies.''
Rheumatoid Arthritis, IL-1, and the IL-1 Cytokine Trap
Rheumatoid arthritis is a chronic disease in which the immune system attacks the tissue that lines and cushions joints. Over time, the cartilage, bone, and ligaments of the joint erode, leading to progressive joint deformity and joint destruction, generally in the hand, wrist, knee, and foot. Joints become painful and swollen and motion is limited. Over two million people, 1% of the U.S. population, are estimated to have rheumatoid arthritis, and 10% eventually become disabled. Women account for two-thirds of these patients.
Rheumatoid arthritis involves an excess of certain cytokines, including IL-1 and tumor necrosis factor (TNF). Drugs that block TNF have already been approved for the treatment of rheumatoid arthritis, while animal studies indicate that IL-1 is also an attractive target for drug development in this disease. Based on preclinical studies, Regeneron's IL-1 Trap is a potent blocker of IL-1 activity, has a long half-life in the blood, penetrates into the inflamed joint, and blocks cartilage erosion in animal models.
While both TNF and IL-1 can induce arthritis, IL-1 more potently induces cartilage destruction in animal models. In addition, the arthritis caused by TNF in some animals can be prevented by blocking the action of IL-1, indicating that the arthritogenic action of TNF may be mediated in part through IL-1. Perhaps even stronger evidence for the role of IL-1 in rheumatoid arthritis is the spontaneously occurring arthritis that occurs in mice that are deficient in the interleukin-1 receptor antagonist (IL-1ra), a naturally occurring blocker of IL-1 action. The validation of IL-1 blockade as a target for drugs to treat rheumatoid arthritis also appears to have been demonstrated by the positive results reported by Amgen Inc. with administration of IL-1ra in clinical trials to patients with rheumatoid arthritis.
In excess, cytokines can be harmful and have been linked to a variety of diseases. Regeneron's research has led to proprietary insights into the mechanism of action of cytokines and to novel approaches to blocking their harmful effects, using what are termed Cytokine Traps. Regeneron has issued patents on 11 Cytokine Traps, including the IL-1 Trap.
Neil Stahl, Ph.D., Vice President, Preclinical Development and Biomolecular Science for Regeneron, said, ``IL-1 is one of the most important of the proinflammatory cytokines that appear to be produced in excess in many diseases. Blocking IL-1 action with the IL-1 Trap may, therefore, be useful in treating a variety of human illnesses in addition to rheumatoid arthritis.'' ... |
