BOULDER, Colo.--(BUSINESS WIRE)--Jul. 31, 2012--
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.”
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.
About Osteoarthritis
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.
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 and inflammatory diseases.
Array has four core proprietary clinical programs: ARRY-614 for
myelodysplastic syndromes, ARRY-520 for multiple myeloma, ARRY-797 for
pain and ARRY-502 for asthma. In addition, Array has 10 partner-funded
clinical programs including two MEK inhibitors in Phase 2 clinical
trials: selumetinib with AstraZeneca and MEK162 with Novartis. For more
information on Array, please go to www.arraybiopharma.com.
Forward-Looking Statement
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 Securities and Exchange Commission. Because these
statements reflect current expectations concerning future events, actual
results could differ materially from those anticipated in these
forward-looking statements as a result of many factors. These factors
include, but are not limited to, the ability of Array to continue to
fund and successfully progress research and development efforts with
respect to ARRY-797; the ability of Array to out-license further
development of ARRY-797 on terms that are favorable to Array; the
willingness of pharmaceutical and biotechnology companies to in-license
drugs for their product pipelines; risks associated with dependence on
collaborators for the clinical development and commercialization of
out-licensed drug candidates; the ability to effectively and timely
conduct clinical trials in light of increasing costs and difficulties in
locating appropriate trial sites and in enrolling patients who meet the
criteria for certain clinical trials; and risks associated with
dependence on third-party service providers to successfully conduct
clinical trials within and outside the United States. Array is providing
this information as of July 31, 2012 and undertakes no duty to update
any forward-looking statements to reflect the occurrence of events or
circumstances after the date of such statements or of anticipated or
unanticipated events that alter any assumptions underlying such
statements.
Source: Array BioPharma Inc.
Array BioPharma Inc.
Tricia Haugeto, 303-386-1193
ir@arraybiopharma.com
