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Array BioPharma’s ARRY-797 Meets Primary Endpoint in Clinical Proof of Concept Trial in Osteoarthritis Patients Whose Pain is Poorly Controlled by NSAIDs
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
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
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
“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,
About the Osteoarthritis Trial
The Phase 2 trial was a 28-day double-blind, active- and placebo-controlled study in 157 patients with osteoarthritis of the knee who had moderate-to-severe chronic pain despite the use of NSAIDs. Patients were randomized (1:1:1) to receive ARRY-797, placebo or oxycodone ER while continuing their use of NSAIDs. The primary endpoint of the trial was the change in the WOMAC® pain subscale from Baseline to Week 4 compared to placebo. Secondary endpoints included safety and pharmacokinetic assessments, WOMAC® physical function subscale, WOMAC® stiffness subscale, responder analysis and the Patient’s Global Impression of Change.
Osteoarthritis, the most common form of arthritis, affects well over 20 million people in the U.S. and results in significant utilization of health care resources. A number of medications are currently available for the treatment of osteoarthritis pain, primarily NSAIDs and opioids; however, a significant unmet medical need remains. Opioids, although providing significant analgesic effects, are limited by tolerability issues (for example, somnolence, nausea, vomiting and constipation) and also suffer from the potential for abuse. NSAIDs offer only partial pain relief and are associated with renal, cardiovascular and gastrointestinal safety concerns.
About ARRY-797 / p38 Inhibitor
ARRY-797 is an orally dosed p38-alpha kinase inhibitor discovered by Array scientists. p38 regulates PGE2 production, a significant pain mediator, and TNF and IL-1 production, both mediators of inflammation. Compared to other p38 inhibitors ARRY-797 has distinct properties; it is highly selective, has exceptional potency in whole blood, has a differentiated pharmacokinetic profile and is highly water soluble. ARRY-797 achieved statistically significant analgesic effects in two Phase 2 acute dental pain studies. ARRY-797 has been generally well-tolerated with over 450 subjects/patients treated. In these largely short duration studies, common adverse events included dizziness, headache, diarrhea and nausea, mostly mild in severity and with no clear relation to dose or duration of exposure. Array believes ARRY-797 has an opportunity to address a significant unmet medical need in both acute and chronic pain.
This press release contains forward-looking statements within the
meaning of the Private Securities Litigation Reform Act of 1995,
including statements about the timing of completion or initiation of
further trials involving ARRY-797, the potential for the results of
ongoing clinical trials to support regulatory approval or the marketing
success of ARRY-797, and future plans to progress, develop and partner
ARRY-797. These statements involve significant risks and uncertainties,
including those discussed in the most recent annual report filed on form
10-K, quarterly reports filed on Form 10-Q, and other reports filed by
Array with the
Array BioPharma Inc.