BOULDER, Colo., Jul 08, 2009 (BUSINESS WIRE) -- Array BioPharma Inc. (NASDAQ: ARRY) today announced top-line results
from its Phase 1 seven-day dose escalation trial up to 1,200 mg daily of
p38 inhibitor, ARRY-797, in healthy volunteers. In addition, the
top-line results were announced in a second study, where ARRY-797 was
evaluated in a 28-day Phase 1b trial in stable rheumatoid arthritis (RA)
patients taking methotrexate. This study compared two doses of ARRY-797
to placebo.
A preliminary analysis of both trials indicates that ARRY-797 was well
tolerated with a pharmacokinetic profile consistent with earlier
studies. In the 28-day, three-arm RA study with a total of 28 patients,
ARRY-797 showed inhibition of CRP levels (marker of inflammation) only
during the first three weeks of dosing and a beneficial reduction in NTx
levels (marker of bone remodeling) throughout the study. In addition,
ARRY-797 showed a trend to improve the patients' assessment of pain (VAS
score) over the course of the study.
"In the 28-day RA study, ARRY-797 demonstrated a transient inhibition of
the inflammatory biomarker CRP and a trend towards analgesic efficacy in
the pain endpoint," said Kevin Koch, Ph.D., President and Chief
Scientific Officer. "Since these results are similar to other p38
inhibitors evaluated in rheumatoid arthritis, these findings have led us
to discontinue testing of ARRY-797 in chronic inflammatory diseases. We
continue to believe that a p38 inhibitor holds promise in treating
patients with cancer and sub-chronic pain."
The Company continues to conduct a full analysis of safety,
pharmacokinetics and efficacy data from both studies. Array anticipates
that complete results from the studies will be presented at a medical
conference in 2010. Based on these preliminary results, Array plans to
cease the enrollment of new patients in its current clinical trial of
ARRY-797 in ankylosing spondylitis patients.
Phase 1b Dose Escalation Trial in Healthy Volunteers: Clinical
Study Design and Results
This Phase 1b dose escalation trial was a randomized, double-blind,
placebo-controlled study in healthy volunteers and was designed to
evaluate the safety and pharmacokinetics of ARRY-797 after single-day
and multiple-day administration of ARRY-797. Single ascending-doses of
900 mg (once) and 1,200 mg/day (800 mg followed by 400 mg 12 hours
later), and multiple-day, ascending-doses of 200, 300 and 400 mg/day TID
(every eight hours) for eight consecutive days were explored.
Safety, Tolerability and Pharmacokinetics: Overall, ARRY-797 was
well-tolerated after single-day and multiple-day administration of total
daily doses of 600 mg, 900 mg, and 1,200 mg. In the multiple-day cohorts
up to 400 mg TID, no adverse event (AE) was reported by more than one
subject in any treatment group and all AEs were considered mild in
intensity. In the single-day cohorts, mild dizziness was reported by two
of the 6 subjects receiving a 900 mg dose of ARRY-797 and moderate
dizziness by one of the 6 subjects receiving 800 mg followed by 400 mg
ARRY-797. Approximately dose-proportional increases in mean total and
peak exposures were observed with increasing dose following single- and
multiple-dose administration. Mean plasma concentrations of ARRY-797
reached steady-state on day two after repeat-dose administration with
modest accumulation.
Phase 1b 28-day Study in Patients with RA: Clinical Study
Design and Results
This Phase 1b trial was a randomized, double-blind, placebo-controlled
design that enrolled 29 patients with RA. Twenty eight patients
completed four weeks of treatment. The trial was conducted at six sites
in the United States. Patients received either 100 mg or 200 mg ARRY-797
twice daily, or placebo. In addition, all patients were on a background
of methotrexate and could receive certain NSAIDs (including COX-2
inhibitors), corticosteroids (low-dose), opioids/analgesics, aspirin, or
acetaminophen. Patients were evaluated every seven days for improvement
in clinical signs and symptoms according three measures: CRP levels
(marker of inflammation), patient's assessment of arthritis pain (VAS
score), and NTx levels (marker of bone remodeling).
Effects on Signs and Symptoms of Rheumatoid Arthritis: The CRP
levels at the 200 mg BID dose of ARRY-797 showed a statistically
significant decrease during the first three weeks of the study but
returned to baseline on week four. Also, the patient's assessment of
pain (VAS score) showed trends to decrease in the 200 mg BID arm. The
NTx levels for both active arms separated from placebo by as much as 30
percent in the 100 mg arm and 50 percent in the 200 mg arm.
Safety, Tolerability and Pharmacokinetics: ARRY-797 was
well-tolerated through 29 days of dosing. There were no premature
discontinuations for serious AEs in any of the study arms. The most
common AEs were generally mild or moderate and were not significantly
different than placebo. Based upon a preliminary assessment, the
exposure of ARRY-797 was consistent with previous studies in healthy
volunteers, there were no apparent drug-drug interactions between
methotrexate and ARRY-797, and no apparent food effect was observed.
ARRY-797 in Acute Pain
The efficacy of ARRY-797 previously was evaluated in two acute
inflammatory pain trials in patients with post-surgical dental pain.
ARRY-797 achieved its primary and secondary endpoints for analgesic
efficacy and was well-tolerated in both trials.
In the first trial, the analgesic effect of 400 mg of ARRY-797, compared
to placebo, was statistically significant based upon the primary
endpoint of total pain relief over six hours post dose (p<0.0001). The
analgesic effect was also statistically significant for total pain
relief over three, eight, 12, and 24 hours post dose. Other analgesic
endpoints, including total pain intensity, time to meaningful pain
relief, and time to analgesia were also significantly improved versus
placebo. Peri-operative dosing with 200 mg before and 200 mg after
surgery also resulted in a substantial reduction in total pain
intensity. Array believes the efficacy observed in this study is due to
the simultaneous inhibition of the pain mediator PGE2 and the
inflammatory mediators TNF, IL-1, and IL-6. No serious AEs were reported
and non-serious adverse events were evenly balanced across the three
groups.
In the second trial, three doses of ARRY-797 (200 mg, 400 mg, and 600
mg) were compared to placebo and celecoxib (400 mg). In the primary
efficacy measure of total pain relief over six hours post dose
(p<0.001), ARRY-797 produced a dose-dependent analgesic response,
compared to placebo. ARRY-797 (400 and 600 mg) and celecoxib (400 mg)
demonstrated significant analgesic benefit, a rapid onset of action
(within 1 hour), and good duration of analgesia.
About ARRY-797 / Pan-cytokine Inhibitor
ARRY-797 is a potent and highly selective p38a inhibitor that decreases
production of PGE2 as well as cytokines such as TNF and IL-1.
The anti-inflammatory and analgesic efficacy of ARRY-797 have been
demonstrated in two previously reported clinical studies using an acute
dental pain model (ACR 2008 Poster #357). In those studies, ARRY-797,
administered orally at the onset of moderate to severe pain, provided a
dose-related analgesic benefit as measured by total pain relief over six
hours following dosing, as well as a profound reduction in post surgical
CRP elevation. The time to onset, magnitude, and duration of analgesia
were similar for ARRY-797 at the two highest doses evaluated (400 mg and
600 mg) and celecoxib 400 mg.
About Pan-cytokine Inhibition for Inflammation and Pain
p38 is a kinase target that regulates the production TNF, IL-1, and IL-6
as well as PGE2. PGE2 is an important mediator of
inflammatory pain and its production is the target of NSAIDs. Many forms
of acute and chronic pain have inflammatory origins, and pan-cytokine
suppression may treat both the inflammation and the resulting pain.
Array believes modulation of all three cytokines plus PGE2 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, and
metabolic diseases. 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.
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 our future plans for advancing certain of our
proprietary drug programs, the potential to earn future milestone
payments, license fees or royalty revenue, and the plans of our
collaborators to further develop drugs we have out-licensed or on which
we are collaborating. These statements involve significant risks and
uncertainties, including those discussed in our annual report filed on
form 10-K for the year ended June 30, 2008, and in other reports filed
by Array with the Securities and Exchange Commission. Because these
statements reflect our current expectations concerning future events,
our 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, our ability to continue to fund
and successfully progress internal research efforts and to create
effective, commercially viable drugs, our ability to achieve and
maintain profitability, the extent to which the pharmaceutical and
biotechnology industries are willing to in-license drug candidates for
their product pipelines and to collaborate with and fund third parties
on their drug discovery activities, our ability to out-license our
proprietary candidates on favorable terms, risks associated with our
dependence on our collaborators for the clinical development and
commercialization of our out-licensed drug candidates, the ability of
our collaborators and of Array to meet objectives tied to milestones and
royalties, and our ability to attract and retain experienced scientists
and management. We are providing this information as of July 8, 2009. We
undertake 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
thaugeto@arraybiopharma.com
