Rigel Pharmaceuticals said it has ended clinical development of its experimental drug R333 after it failed a Phase II study assessing its effect on the skin disease discoid lupus erythematosus (DLE), and will instead refocus on launching two Phase III trials for its drug candidate fostamatinib for the bleeding disorder immune thrombocytopenic purpura (ITP).
Rigel said R333, a topical dermatological JAK/SYK inhibitor, failed to meet its primary endpoint in the Phase II study. After four weeks of treatment, fewer DLE patients than expected achieved at least a 50% decrease in active skin lesions from baseline with respect to the total combined erythema-and-scaling score of all treated lesions.
"Unfortunately, discoid lupus is a difficult indication and R333 didn't provide the benefit we had hoped. However, this frees up resources to focus on our ITP and dry eye programs," Rigel Chairman and CEO James M. Gower said in a statement.
R333 is the third Rigel drug candidate whose development has seen clinical trial failures this year. In June, AstraZeneca returned products rights for fostamatinib to Rigel and ended a partnership launched in 2010 to develop the compound for rheumatoid arthritis—a collaboration the partners said at the time could net up to $1.25 billion, plus royalties, for Rigel. The termination followed mixed results from three OSKIRA Phase III trials.
In August, Rigel’s R343 failed to show effectiveness against allergic rhinitis in a Phase II study the company conducted alone, after Pfizer ended a collaboration for the drug in 2011. R343 failed to meet its primary or secondary endpoints or did not meet the primary endpoint in a Phase II study—the change in pre-bronchodilator FEV1 (a measure of lung function) from baseline to dosing completion at week 8, compared to active doses to placebo. R343 was shown to be relatively safe and well tolerated at the two doses studied.
Rigel responded to the setbacks by eliminating 30 employees or 18% of its workforce, “mostly in the drug discovery area,” the company said in September.
Gower said Rigel will shift its clinical attention to fostamatinib, an oral SYK inhibitor. Following an end-of-Phase II meeting with FDA regulators, the company said it expects in the first half of 2014 to begin the two Phase III trials. Each is expected to enroll about 75 patients who would be treated for six months, then have the option to enroll in an extension study.
Both trials will include randomized, placebo-controlled, enrollment-verified ITP patients with platelet counts below 30,000 platelets per microliter of blood. The goal of the trials will be to achieve a durable platelet count increase to over 50,000 platelets per microliter of blood.
“We now have a clear picture of the Phase III program for fostamatinib in ITP, and we plan to start the studies early next year,” Gower said.
Rigel anticipates top line data from the studies to emerge in 2015.
Fostamatinib is one of five product candidates under development at Rigel. In addition to fostamatinib, they include R348, a topical JAK/SYK inhibitor for dry eye that is now in Phase II clinical trials; R118, an AMPK activator entering Phase I early next year; and two oncology product candidates in Phase I development with partners BerGenBio and Daiichi Sankyo.