Array BioPharma announces positive results from ARRY-797 Phase 2 trial on osteoarthritis

Array BioPharma (NASDAQ: ARRY) today announced that ARRY-797 met its primary endpoint in a randomized, placebo-controlled and active-controlled (oxycodone ER) Phase 2 clinical trial in 157 osteoarthritis patients suffering from moderate to severe knee pain despite the use of non-steroidal anti-inflammatory drugs (NSAIDs). Patients in all treatment groups continued using NSAIDs throughout the trial.

The investigational compound, ARRY-797, is a novel, oral, selective p38 inhibitor with a mechanism of action unique from that of currently approved pain medications.

Treatment with ARRY-797 resulted in a statistically significant reduction in pain over a 28-day period compared to placebo, as measured using the Western Ontario and McMaster Universities Arthritis Index (WOMAC^®) pain subscale (a 0 - 10 numerical pain rating scale). Patients receiving ARRY-797 experienced a mean reduction in the WOMAC^® pain subscale score at day 28 vs. baseline that was 0.8 greater than those receiving placebo (2.4 vs. 1.6; one-sided p = 0.0247). Additional endpoints, including WOMAC^® physical function, WOMAC^® stiffness, responder analysis and the Patient's Global Impression of Change, also showed improvement relative to placebo.

Oxycodone ER was used as the active control for the trial. A higher discontinuation rate due to adverse events was observed in patients treated with oxycodone ER (34%) than for either the ARRY-797 (6%) or placebo (8%) treatment groups. In patients completing the trial, the reduction in WOMAC^® pain observed for ARRY-797 was comparable to that seen with oxycodone ER.

"The study results with ARRY-797 showed promising benefit in the management of pain in osteoarthritis patients who are refractory to NSAIDS," said Alan Kivitz, M.D., founder of the Altoona Arthritis and Osteoporosis Center and an investigator on the study. "This study was designed with a high hurdle in mind, which this drug was able to overcome."

In this trial, ARRY-797 was considered overall to be well-tolerated at the selected dose of 400 mg twice-daily. The most common adverse events observed in patients treated with ARRY-797 were dizziness, diarrhea and nausea, which were mainly mild in severity. ARRY-797 treatment was associated with sporadic, transient increases in creatine kinase and aspartate aminotransferase. Mild prolongations of the QTc interval and sustained decreases in systolic and diastolic blood pressure were also observed.

To further explore the safety and tolerability of ARRY-797, Array is currently conducting a multiple ascending dose trial in healthy volunteers at doses up to 2.5-fold higher than those evaluated in the osteoarthritis pain trial. ARRY-797 has been well-tolerated in this trial to date, and greater QTc prolongations were observed at these higher dose levels. No subject in either trial exhibited an absolute QTc interval >500 msec or a change from baseline >60 msec, two values cited by regulatory authorities, including the FDA, as thresholds of particular concern for cardiac arrhythmia. These QTc observations warrant further evaluation.

"These results, together with our earlier studies in acute pain, provide evidence that ARRY-797 delivers therapeutic utility in both acute and chronic pain settings," said Ron Squarer, Chief Executive Officer, Array BioPharma. "Given the scope of a development program in pain, Array will aggressively seek a partner to maximize the value of this drug."