Lexicon files investigational NDA for LX2931 in rheumatoid arthritis

Nov 13 2007

Lexicon Pharmaceuticals, Inc. has announced that it has submitted an investigational new drug (IND) application to the U.S. Food and Drug Administration (FDA) for LX2931, an oral drug candidate for rheumatoid arthritis and other autoimmune conditions.

The initial Phase 1 clinical trial of LX2931 is planned as a double-blind, randomized, placebo-controlled, ascending single-dose study in healthy volunteers, designed to evaluate the safety, tolerability, and pharmacokinetics of LX2931. Lexicon expects to initiate clinical trials with LX2931 following FDA review.

"As an orally-delivered modulator of lymphocyte activity, we believe LX2931 has potential to be an important new therapy for rheumatoid arthritis and other autoimmune disorders," said Philip M. Brown, M.D., J.D., vice president of clinical development at Lexicon. "We can now add immunology to the list of therapeutic areas with clinical-stage compounds from Lexicon's drug discovery pipeline."

Rheumatoid arthritis is an autoimmune disorder characterized by stiffness, pain, swelling, and limitation of motion in multiple joints. More than 2 million Americans suffer from rheumatoid arthritis, which, if left untreated, can result in disfigurement and disability from irreversible joint damage. According to the National Institutes of Health (NIH), autoimmune disorders affect between 14.7 and 23.5 million people in the United States.

LX2931 was developed at Lexicon as an inhibitor of a key enzyme in the sphingolipid pathway, which controls lymphocyte circulation and trafficking to peripheral sites in the body during an inflammatory response. As with Lexicon's other clinical and preclinical programs, the LX2931 target enzyme was identified through Lexicon's gene knockout program, Genome5000(TM). Knockout mice lacking this enzyme had a significantly decreased number of circulating lymphocytes and were resistant to inflammation in a wide range of assays modeling processes involved in the development of arthritis and other autoimmune conditions. Because inappropriate activation of lymphocytes is associated with autoimmune disorders, including rheumatoid arthritis, reduction of lymphocyte buildup at sites of disease activity holds promise as a new therapeutic mechanism. Preclinical studies with LX2931 showed a robust and reproducible reduction of inflammation in animal models of arthritis. Additionally, LX2931-treated animals showed a rapid, dose-dependent reduction in peripheral lymphocyte counts.