Rigel Pharmaceuticals, Inc., a clinical-stage drug development company that discovers and develops novel, small-molecule drugs for the treatment of inflammatory and autoimmune diseases, as well as muscle disorders, said  that two of its lead product candidates entered clinical trials during the fourth quarter of 2011.

The company is evaluating R548, an oral JAK3 inhibitor, as a potential therapeutic for transplant rejection and other systemic immune disorders. The second candidate, R333, is a topical JAK/SYK inhibitor aimed at treating various phases of discoid lupus (lupus of the skin).

"Rigel continues to be one of the most productive companies in the biopharmaceutical sector, as evidenced by the commencement of First in Human (FIH) studies in two programs this past quarter," said James M. Gower, chairman and chief executive officer of Rigel. "The goal of our highly-talented 155 person R&D-focused organization is to add at least one new product candidate into the clinic each year for the foreseeable future and move those into proof-of-concept trials. We plan to have phase 2 trial results in three internal programmes in 2013," he added.

Transplant rejection is an area of tremendous medical need. While 90% of patients survive the first year after receiving the transplanted organ, chronic organ rejection rates rise to 50% within the five to ten years following surgery. Currently available therapeutics are not sufficient to help these patients achieve lasting recovery. Furthermore, transplants of certain organs are rarely done because of the inadequacies of these therapies. Rigel's R548 is a JAK3 inhibitor that is expected to moderate the immune system's response to the allograft and improve patient outcomes. R548 may also have application in treating other immune system disorders. Phase 1 clinical studies in normal healthy volunteers began in the fourth quarter of 2011.

Discoid Lupus Erythematosus (DLE) is an autoimmune system disorder of the skin. Inflamed disk-shaped sores on the face, chest and scalp, which may result in scaring, swelling and hair loss, characterize DLE. This disorder has an acute phase, which research has connected to SYK kinase signalling within the immune cascade. There is also a chronic phase of the disorder due to the abundance of JAK signalling. The current treatment options available for discoid lupus are few and have toxicities that further limit their use. In December 2011, Rigel began a phase 1 clinical trial of R333, a topical JAK/SYK inhibitor, which may be useful in treating both phases of this potentially disfiguring disorder.  

In addition to the above clinical programs, Rigel expects to initiate a phase 2 trial with R343, an inhaled SYK inhibitor, for patients with allergic asthma in mid-2012. This multi-center, multiple dose, placebo controlled study is expected to include approximately 300 asthma patients.  R343 will be delivered directly into the lungs via a dry inhalation device. Rigel will share additional information about its plans for R343 in future announcements.

In the meantime, Rigel's collaborator on fostamatinib, AstraZeneca (AZ), has indicated that the phase 3 studies in rheumatoid arthritis are continuing as planned. The first of the OSKIRA (Oral SYK Inhibition in Rheumatoid Arthritis) studies, OSKIRA-1, completed full enrollment in the fourth quarter of 2011. OSKIRA-1 is a 12-month clinical trial of approximately 900 patients studying two dosing regimens of fostamatinib compared to placebo in patients who are not achieving an adequate response with methotrexate alone. AZ expects to file a New Drug Application for fostamatinib in the US and a European equivalent in 2013. The companies will provide more specific timing as that milestone approaches.