Array BioPharma Inc announced its preliminary analysis of results from a study examining ARRY-162, a small molecule MEK inhibitor, in a 12-week phase-2 clinical trial with 201 patients. The patients had active rheumatoid arthritis (RA) that was not completely responsive to methotrexate. This study included a placebo group and three different dose groups of ARRY-162, all on a stable background of methotrexate. None of the treatment groups demonstrated a statistically significant ACR20 response rate compared to the placebo group at 12 weeks (p=0.459), therefore the study did not meet the primary endpoint.
Overall, the placebo response rates in this study were higher than expected for this patient population and showed regional differences, with patients in South America (99 patients) having substantially higher placebo response rates than those in Eastern Europe (101 patients). In Eastern Europe when patients in the three active treatment arms were combined, there was a trend towards efficacy, as measured by DAS28-4(CRP) (p=0.067), 'Good' Eular response (p=0.105) and ACR20 response rate (p=0.115). Array is conducting a full analysis of safety, efficacy and pharmacokinetic data from this study and expects to present complete results at a medical conference in 2010.
"This is the first clinical trial evaluating the modulation of the MEK pathway for the treatment of chronic inflammatory disease," said Kevin Koch, president and chief scientific officer. "While we are disappointed in the overall efficacy outcome, we were pleased with the confirmation of the favourable safety profile and are continuing to evaluate the regional results. Previously we announced our strategy to rapidly advance ARRY-162 for the treatment of cancer patients. We initiated a phase 1 oncology trial last month and patient dosing is underway."
ARRY-162, an orally active MEK inhibitor, has shown significant efficacy and is well tolerated in preclinical models of human arthritis and other inflammatory diseases. In preclinical combination studies with standard of care RA treatments, including methotrexate, dexamethasone, ibuprofen, and etanercept, ARRY-162 was well tolerated and demonstrated at least additive efficacy, even with the maximally efficacious dose of etanercept. ARRY-162 was well-tolerated in preclinical studies for up to 9 months of daily dosing. Phase 1 clinical trials with ARRY-162 have demonstrated selective and dose-dependant inhibition of IL-1, IL-6 and TNF with convenient oral dosing, as well as good tolerability when used in combination with methotrexate.
Array believes ARRY-162 is particularly well-suited for use in cancer treatment and has advantages over other MEK inhibitors currently in development, including greater potency, and improved safety and pharmacokinetics.
MEK is a key protein kinase in the RAS/RAF/MEK/ERK pathway, which mediates production of key proinflammatory cytokines, including TNFa, IL-1ß and IL-6, as well as cellular proliferation and survival.
Array BioPharma is a biopharmaceutical company focused on the discovery, development and commercialization of targeted small-molecule drugs to treat patients afflicted with cancer, inflammatory diseases, pain and metabolic diseases.