New Mechanisms of Action
Rheumatoid arthritis and other autoimmune diseases
LX2931 is an orally-delivered small molecule inhibitor of sphingosine-1-phosphate lyase (S1P lyase), an enzyme in the sphingosine-1-phosphate (S1P) pathway associated with the body's inflammatory response. Inappropriate inflammatory cell response is associated with autoimmune diseases, a spectrum of disorders in which the immune system malfunctions and causes the body to attack its own organs, tissues, and cells. LX2931 is under development for the potential treatment of autoimmune diseases such as rheumatoid arthritis.
LX2931 regulates lymphocytes by targeting S1P lyase, the enzyme that degrades S1P. The secreted messenger, S1P, interacts with S1P receptors such as S1P1 to regulate lymphocyte migration from lymphoid tissues (e.g., thymus and spleen). In preclinical models, inhibition of S1P lyase by LX2931 caused the concentration of S1P to rise in preferentially in lymphoid tissues, thereby reducing inflammation.
Results from a Phase 2 study of LX2931 in patients with rheumatoid arthritis indicated that all doses were well tolerated and patients treated with 150 mg of LX2931 once daily showed an improvement in the primary efficacy endpoint, the percentage of patients achieving an American College of Rheumatology 20 (ACR20) response at week 12. Additional post-hoc analysis revealed that patients with plasma levels of LX2931 >60 ng/ml had a statistically significant improvement in ACR20 scores (p<0.001) compared to those with lower plasma concentrations.
For more detailed information regarding the Phase 2 study, please see our press release here.
LX2931 has recently completed a dose escalation trial in patients with rheumatoid arthritis. LX2931 was well-tolerated and showed signals of clinical benefit.
About Rheumatoid Arthritis
Autoimmune and inflammatory diseases, such as rheumatoid arthritis multiple sclerosis and systemic lupus, result when the body’s immune system attacks its own organs, tissues and cells causing tissue damage (see figure). A substantial portion of the population suffers from these diseases, which are often chronic, debilitating, and life-threatening. Rheumatoid arthritis is a common autoimmune disease characterized by an inappropriate immune system attack on the joints. Symptoms include fever, malaise, fatigue, pain, stiffness, and eventually deformation of the joints.
The body's own immune system attacks a joint's synovial membrane, which becomes inflamed, secretes fluid, and the cartilage becomes rough and pitted.
Rheumatoid Arthritis Prevalence
According to the National Institutes of Health (NIH), more than 1 million Americans suffer from rheumatoid arthritis. If left untreated, rheumatoid arthritis can result in disfigurement and disability from irreversible joint damage. Autoimmune disorders, collectively, affect between 14.7 and 23.5 million people in the United States.
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* This drug candidate is currently undergoing human clinical studies; safety and efficacy have not been evaluated by any regulatory authorities for the indications described.