-- Data Presented at 2008 ACR/ARHP Annual Scientific Meeting --
BOULDER, Colo.--(BUSINESS WIRE)--Oct. 26, 2008--Array BioPharma
Inc. (Nasdaq: ARRY) today announced positive results from a Phase 2
acute inflammatory dental pain study evaluating the analgesic efficacy
of ARRY-797, a small molecule p38 inhibitor, at the 2008 ACR/ARHP
Annual Scientific Meeting in San Francisco, Calif. These results
confirm a smaller Phase 2 dental pain study reported in May 2008 in
which ARRY-797 demonstrated significant analgesic benefit when
administered either prior to or following surgery.
This Phase 2 randomized study enrolled 253 patients with
postsurgical pain. 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 less
than 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, robust pain relief, and
good duration of analgesia (see table below).
Median time Median time
Pain to onset to rescue
Pain Relief Intensity of analgesia medication
(TOTPAR6)(1) (2)(mm) (min.) (hrs)
----------------------------------------------------------------------
Placebo 2.56 71.0 not reached 1.6
----------------------------------------------------------------------
ARRY-797 / 200 not reached
mg 5.98 56.7 4.0
----------------------------------------------------------------------
ARRY-797 / 400
mg 8.89 44.3 60.5 6.6
----------------------------------------------------------------------
ARRY-797 / 600
mg 9.48 37.2 43.5 6.2
----------------------------------------------------------------------
Celecoxib /
400 mg 8.58 45.4 65.0 7.2
----------------------------------------------------------------------
(1) Total Pain Relief over 6 hours post dose
(2) Mean pain intensity on a Visual Analog Scale (0 to 100 mm)
measured at 3 hours post dose
In patients requiring rescue medication six to eighteen hours
following dosing, administration of a second 200 mg dose of ARRY-797
resulted in statistically significant pain relief compared to placebo
(p less than 0.008). No serious adverse events were reported in the
ARRY-797 treated groups, and the overall incidence of adverse events
was similar across all treatment groups. In the management of acute
pain, the recommended dose of celecoxib is 400 mg initially, followed
by an additional 200 mg dose if needed on the first day. On subsequent
days, the recommended dose is 200 mg twice daily as needed.
Also at the conference, Array presented results from two previous
ARRY-797 trials. In the first Phase 2 dental pain study, CRP levels, a
biomarker of systemic inflammation and cardiovascular disease, were
measured. Compared to placebo, ARRY-797 reduced CRP by 85% on the day
following surgery. In a Phase 1 study, ARRY-797 significantly
inhibited the inflammatory cytokines TNF and IL-1 and the pain
mediator PGE2 out to 24 hours post-dose.
"These results, together with our multiple-dose, 14-day trial in
healthy volunteers, confirm that ARRY-797 is well-tolerated at doses
that provide acute analgesic benefit and systemic anti-inflammatory
activity," said Kevin Koch, Ph.D., President and Chief Scientific
Officer, Array BioPharma. "In view of our tolerability profile, we are
exploring higher doses of ARRY-797 and evaluating additional trials in
sub-chronic pain indications."
Array is also conducting a 12-week study of ARRY-797 in ankylosing
spondylitis (AS), a painful inflammatory condition, which will begin
patient recruitment before the end of 2008. This study will enroll
over 160 patients and is planned to provide efficacy data in the first
half of 2010. The reported positive analgesic results, coupled with
the inflammatory cytokine inhibition, provide additional support for
the potential clinical benefit to AS patients.
The ARRY-797 posters will be available as PDFs after they are
presented at ACR/ARHP on Array's website:
www.arraybiopharma.com/PatentsPublications/Default.asp?PBCategoryID=3.
Phase 2 Inflammatory Pain Study Design
This Phase 2 trial was a randomized, double-blind, active- and
placebo-controlled, parallel-group dose-range finding analgesic
efficacy trial of ARRY-797. Patients underwent elective dental surgery
to remove 3 or more impacted third molars. Following surgery and the
development of moderate to severe pain, patients were randomized to
receive either ARRY-797 (200 mg, 400 mg or 600 mg), placebo, or
celecoxib (400 mg). In patients requiring rescue medication six to
eighteen hours following dosing, a second dose of either 200 mg
ARRY-797 or placebo was administered.
About ARRY-797 / p38 Inhibitor
ARRY-797 is a highly selective, orally dosed, p38-alpha kinase
inhibitor, which modulates the production of several inflammatory
mediators in human whole blood with nanomolar potency. ARRY-797 has
distinct properties compared to other p38 inhibitors; in particular,
exceptional potency in whole blood coupled with a unique
pharmacokinetic and distribution profile.
In Phase 1 studies in healthy volunteers, ARRY-797 demonstrated
linear increases in exposure with increasing oral doses from 25 to 400
mg. During 14-day treatment periods, the drug was well-tolerated at
all doses tested. In blood samples taken from these volunteers,
ARRY-797 dose-dependently inhibited the LPS-stimulated production of
the inflammatory cytokines, TNF and IL-1, as well as PGE2, a key
mediator of pain. In Phase 2 acute inflammatory pain trials, ARRY-797
was well-tolerated, demonstrated clinically meaningful analgesic
benefit, as well as a significant reduction in CRP levels, a biomarker
of systemic inflammation. Array plans to initiate a Phase 2 study of
ARRY-797 in patients with ankylosing spondylitis by the end of 2008
and will explore higher doses of ARRY-797 to support the potential use
of this agent in additional sub-chronic pain indications.
About p38 Inhibition for Inflammation and Pain
P38-alpha is an intracellular protein kinase that regulates the
production of, and response to, inflammatory mediators, such as TNF,
IL-1 and IL-6, as well as the pain mediator PGE2. Injectable biologic
agents which regulate the actions of TNF, IL-1 and IL-6 are all
clinically validated drugs used in controlling inflammation in
rheumatoid arthritis and several related inflammatory diseases. PGE2
is an important inducer of inflammatory pain and its production is
blocked by commonly used NSAIDs like ibuprofen. Many forms of acute
and chronic pain have inflammatory origins, and pan-cytokine
suppression may treat both the inflammation and the resulting pain and
tissue damage. 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 joint/tissue destruction and 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, the expected progress and
success of our internal proprietary drug discovery activities and the
development activities of our collaborators, 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,
including clinical trials, tied to milestones and royalties, and our
ability to attract and retain experienced scientists and management.
We are providing this information as of October 26, 2008. 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.
CONTACT:
Array BioPharma Inc.
Tricia Haugeto, 303-386-1193
ir@arraybiopharma.com
SOURCE: Array BioPharma Inc.
