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Array BioPharma Inc. today announced that its Chief Medical Officer, John Yates, M.D., presented additional positive results from a Phase 2 clinical trial evaluating the efficacy of ARRY-797, a novel small molecule pan-cytokine inhibitor, in patients with post-surgical dental pain at the American Pain Society's 27th Annual Scientific Meeting in Tampa, Florida
BOULDER, CO, USA | May 7, 2008 | Array BioPharma Inc. (Nasdaq: ARRY) today announced that its Chief Medical Officer, John Yates, M.D., presented additional positive results from a Phase 2 clinical trial evaluating the efficacy of ARRY-797, a novel small molecule pan-cytokine inhibitor, in patients with post-surgical dental pain at the American Pain Society's 27th Annual Scientific Meeting in Tampa, Florida.
ARRY-797 achieved its primary and secondary endpoints for analgesic effect and was well-tolerated in this Phase 2 clinical trial. The analgesic effect of 400 mg of ARRY-797 administered after surgery, compared to placebo, was statistically significant based upon the primary endpoint of total pain relief over six hours (10.28 for ARRY-797 vs. 3.85 for placebo; p less than 0.0001). The analgesic effect was also statistically significant for total pain relief over three, eight, 12 and 24 hours after dosing.
The pain intensity score, which is measured on a visual analog scale from 0 to 100 mm, also demonstrated significant differentiation between ARRY-797 and placebo for all time periods studied. The area under the curve for pain intensity between zero and six hours was significantly lower for patients receiving ARRY-797 both before and after surgery (200 mg per dose), and after surgery (400 mg) vs. placebo (p=0.0020 and p=0.0013, respectively). At three hours after surgery, the pain intensity was 31.5 mm lower in the group receiving ARRY-797 (400 mg) after surgery compared to placebo. Patients in this group also reported faster time to meaningful pain relief (p=0.006) and time to onset of analgesia (p=0.0017) relative to placebo.
Based on study results, Array has begun a second Phase 2 acute inflammatory pain trial in 250 patients comparing three doses of ARRY-797 (200, 400 and 600 mg) with both placebo and with an active comparator, celecoxib (400 mg). Array is also planning a 12-week study of ARRY-797 in ankylosing spondylitis (AS), which will begin patient recruitment in the fall of 2008. This study will enroll 140 patients and is planned to provide efficacy data by the fall of 2009. In addition, Array is initiating a 28-day study of ARRY-797 in 30 rheumatoid arthritis patients on stable doses of methotrexate. The primary endpoints are safety, tolerability and pharmacokinetics.
"Our scientific rationale for the trial was that ARRY-797's ability to simultaneously inhibit several inflammatory mediators, including PGE-2, TNF, IL-1 and IL-6, would result in clinically meaningful pain relief," said Dr. Yates. "We believe these impressive trial results demonstrate the potential of this drug to suppress inflammation and treat signs and symptoms in a wide variety of inflammatory diseases."
Phase 2 Inflammatory Pain Study Design
The Phase 2 trial was a randomized, double-blind, placebo-controlled, parallel-group efficacy study of ARRY-797 in patients undergoing third molar extraction. This is a standard model for testing efficacy of analgesic agents. The study objective was to assess the analgesic efficacy, safety and tolerability of ARRY-797 dosed either after the operation (400 mg) or both before and after surgery (200 mg twice). The trial enrolled 103 patients and was conducted at two centers in the United States.
About ARRY-797 / Pan-cytokine Inhibitor
ARRY-797 is a highly selective p38-alpha inhibitor, which modulates the production of several inflammatory mediators in human whole blood with nanomolar potency. ARRY-797 has unique properties, including high water solubility and tissue penetration, and was designed to limit distribution to the central nervous system.
In Phase 1 studies in healthy volunteers of up to 14 days dosing, ARRY-797 demonstrated linear increases in exposure with increasing oral doses from 25 to 400 mg. The drug was well-tolerated at all doses tested with no serious adverse events. In blood samples taken from these volunteers and treated with LPS, ARRY-797 dose-dependently inhibited the stimulated production of TNF, IL-1, IL-6 and PGE-2.
About Pan-cytokine Inhibition for Inflammation and Pain
P38 is a target that regulates the production of TNF, IL-1, IL-6 and PGE-2. TNF, IL-1 and IL-6 are all clinically validated cytokines for controlling inflammation in rheumatoid arthritis and are prevalent in many forms of inflammation. PGE-2 is an important mediator of inflammatory pain and the target of NSAIDs. Many forms of acute and chronic pain have inflammatory origins. Array believes modulation of all of these inflammatory mediators simultaneously may be more effective than inhibition of any one in isolation for controlling both the underlying inflammation and the resulting symptoms such as pain.
About Array BioPharma
Array BioPharma Inc. is a biopharmaceutical company focused on the discovery, development and commercialization of targeted small molecule drugs to treat patients afflicted with cancer, inflammatory diseases and pain. Our proprietary drug development pipeline includes clinical candidates that are designed to regulate therapeutically important target proteins and are aimed at significant unmet medical needs. In addition, leading pharmaceutical and biotechnology companies collaborate with Array to discover and develop drug candidates across a broad range of therapeutic areas. For more information on Array, please go to www.arraybiopharma.com.
SOURCE: Array BioPharma Inc. |
