Autoimmune diseases
Elan’s therapeutic strategy for treating autoimmune and other diseases is to identify mechanisms common to these diseases and develop novel therapeutics that may stop or interfere with the underlying causes of disease. Even after our drugs are approved, Elan continues to study their safety and effectiveness to continually improve our ability to benefit patients.
Multiple Sclerosis
Nearly 20 years ago, Elan scientists made the breakthrough discovery of how white blood cells are able to enter the brains of people with multiple sclerosis (MS) and destroy nerve cells. Alpha 4 integrin is a protein expressed by immune cells that allows immune system cells to leave the bloodstream and invade target tissues. Blocking alpha 4 integrin stops immune cells from entering tissues. Since first publishing the hypothesis concerning the therapeutic potential of blocking alpha 4 integrin in 1992, our scientists have been expanding and refining scientific understanding of how cells enter tissues. Through this deep understanding, we have developed small molecules that can selectively block particular alpha 4 integrin interactions. We have advanced a number of compounds in this area. ELND002 is being studied for MS and hematologic malignancies, and ELND004 is being studied for ulcerative colitis and Crohn’s disease.
The discovery of the role of alpha 4 integrin led to the development of TYSABRI® (natalizumab), which provides another treatment option for patients with relapsing forms of MS. TYSABRI is a monoclonal antibody that blocks alpha 4 integrin from inducing immune cells to leave the bloodstream. TYSABRI also prevents these immune cells from migrating into chronically inflamed tissue where they may cause or maintain inflammation.
The FDA approved TYSABRI in November 2004 to treat patients with relapsing forms of multiple sclerosis. TYSABRI was voluntarily removed from the market in early 2005 after three patients contracted progressive multifocal leukoencephalopathy (PML), a serious, rare opportunistic viral brain infection.
In June 2006, the FDA approved the reintroduction of TYSABRI as a monotherapy to treat relapsing forms of MS. Approval for the marketing of TYSABRI in the European Union was also received in June 2006. The distribution of TYSABRI in both the United States and European Union began in July 2006. In the United States, Europe and the rest of the world, provisions are in place to ensure patients are informed of the risks associated with TYSABRI therapy, including progressive multifocal leukoencephalopathy (PML), and to enhance collection of post-marketing data on the safety and utilization of TYSABRI for MS.
Elan scientists are also looking at mechanisms beyond alpha 4 integrin to identify novel therapies addressing unmet medical needs of secondary progressive MS patients. We have ongoing discovery research efforts focused on understanding the relationship between the brain inflammation and neurodegeneration characteristic of patients with advanced MS. This work includes a drug discovery program targeting a cell signaling molecule that is believed to be associated with chronic brain inflammation in MS patients.
TYSABRI Prescribing Information
Crohn’s disease
After discovering that alpha 4 integrin plays a central role in the inflammatory responses associated with MS, Elan scientists explored whether the protein might be involved in other inflammatory diseases. Elan evaluated TYSABRI as a treatment for Crohn’s disease (CD) in collaboration with Biogen Idec. The safety and efficacy of TYSABRI as both an induction and maintenance therapy were evaluated in 11 clinical studies, including three pivotal, randomized, double-blind, placebo-controlled, multi-center trials.
In January 2008, the FDA approved the supplemental Biologics License Application (sBLA) for TYSABRI for inducing and maintaining clinical response and remission in adult patients with moderately to severely active CD, with evidence of inflammation, who have had an inadequate response to, or are unable to tolerate, conventional CD therapies and inhibitors of TNF-alpha. Elan launched TYSABRI for the treatment of Crohn’s disease in the United States in the first quarter of 2008.