Preclinical data demonstrates activity against
all tested ALK mutants
Additional Publication in the Journal of
Medicinal Chemistry Describes Chemical Design Elements of
Brigatinib
ARIAD Pharmaceuticals, Inc. (NASDAQ: ARIA) today announced the
publication of preclinical data on brigatinib, its investigational
oral tyrosine kinase inhibitor in development for the treatment of
patients with anaplastic lymphoma kinase positive (ALK+) metastatic
non-small cell lung cancer (NSCLC). The design and preclinical
characterization of brigatinib are described in an article titled,
“The Potent ALK Inhibitor Brigatinib (AP26113) Overcomes Mechanisms
of Resistance to First- and Second-Generation ALK Inhibitors in
Preclinical Models,” in the journal Clinical Cancer Research
(Zhang, S.; et al. Clin Cancer Res. 2016, DOI:
10.1158/1078-0432.CCR-16-0569 Published 25 October 2016).
Activating gene rearrangements in ALK account for approximately
three to seven percent of NSCLCs. Disease progression in patients
treated with the first-generation ALK inhibitor crizotinib can be
associated with secondary resistance mutations in ALK, or the
development of brain metastases. Resistance mutations in ALK,
including G1202R, have also been associated with disease
progression in patients treated with the second-generation ALK
inhibitors ceritinib and alectinib. In the preclinical studies
described in the paper, brigatinib was shown to be a highly potent
and selective inhibitor of ALK, inhibiting ALK at lower
concentrations than crizotinib, ceritinib, and alectinib.
Furthermore, in these studies, brigatinib was the only inhibitor
that showed activity against all 17 tested ALK mutants that have
been associated with preclinical or clinical resistance to existing
ALK inhibitors, including G1202R. In addition, compared to
crizotinib, brigatinib was shown to significantly prolong survival
of mice with ALK+ tumors in the brain.
“We believe that these preclinical findings support a molecular
basis for the promising systemic and intracranial activity in ALK+,
crizotinib-resistant NSCLC patients being treated with brigatinib
in clinical trials and further validate our ongoing clinical
research to understand the potential of brigatinib to address
mutations associated with disease progression,” said Victor M.
Rivera, Ph.D., vice president of preclinical & translational
research at ARIAD. “In addition, we believe that these findings
support testing brigatinib as initial therapy in ALK+ NSCLC
patients, to see if the greater in vitro potency of brigatinib also
manifests in human trials as deeper and more durable responses
compared to crizotinib, and whether emergence of ALK resistance
mutations can be delayed or even circumvented.”
ARIAD has commenced the Phase 3 ALTA 1L clinical trial to
compare brigatinib and crizotinib in ALK+ NSCLC patients who have
not received prior ALK inhibitors.
Brigatinib Medicinal Chemistry Publication
In addition, the medicinal chemistry strategy leading to the
discovery of brigatinib was published in an article titled,
“Discovery of Brigatinib (AP26113), a Phosphine Oxide-Containing,
Potent, Orally Active Inhibitor of Anaplastic Lymphoma Kinase,” in
the Journal of Medicinal Chemistry, (Huang, W.-S.; et al. J. Med.
Chem. 2016, 59, DOI: 10.1021/acs.jmedchem.6b00306).
“This publication details, for the first time, specific design
elements that ARIAD scientists utilized in synthesizing brigatinib.
Brigatinib features an innovative phosphine oxide recognition motif
that is designed to enhance potency and selectivity while also
conferring favorable pharmacologic properties,” said William C.
Shakespeare, Ph.D., vice president of drug discovery at ARIAD.
“Brigatinib is the only phosphine oxide-containing molecule to have
advanced to late stage clinical trials, showcasing how our
innovative chemistry platform can deliver novel drug candidates
designed to tackle challenging clinical problems.”
About Non-Small Cell Lung Cancer and ALK
Non-small cell lung cancer (NSCLC) is the most common form of
lung cancer, accounting for approximately 85 percent of the
estimated 228,190 new cases of lung cancer diagnosed each year in
the United States, according to the American Cancer Society.
Anaplastic lymphoma kinase (ALK) was first identified as a
chromosomal rearrangement in anaplastic large-cell lymphoma (ALCL).
Genetic studies indicate that chromosomal rearrangements in ALK are
key drivers in a subset of NSCLC patients as well. Since ALK is
generally not expressed in normal adult tissues, we believe that it
represents a promising molecular target for cancer therapy.
Approximately three to eight percent of patients with NSCLC have a
rearrangement in the ALK gene.
About Brigatinib
Brigatinib is an investigational, targeted cancer medicine
discovered internally at ARIAD Pharmaceuticals, Inc. It is in
development for the treatment of patients with anaplastic lymphoma
kinase positive (ALK+) non-small cell lung cancer (NSCLC) whose
disease is resistant or intolerant to crizotinib. Brigatinib is
currently being evaluated in the global Phase 2 ALTA trial that is
the basis for its initial regulatory review. ARIAD has also
initiated the Phase 3 ALTA 1L trial to assess the efficacy and
safety of brigatinib in comparison to crizotinib in patients with
locally advanced or metastatic ALK+ NSCLC who have not received
prior treatment with an ALK inhibitor. More information on
brigatinib clinical trials, including the expanded access program
(EAP) for ALK+ NSCLC can be found here.
About ARIAD
ARIAD Pharmaceuticals, Inc., headquartered in Cambridge,
Massachusetts, is focused on discovering, developing and
commercializing precision therapies for patients with rare cancers.
ARIAD is working on new medicines to advance the treatment of rare
forms of chronic and acute leukemia, lung cancer and other rare
cancers. ARIAD utilizes computational and structural approaches to
design small-molecule drugs that overcome resistance to existing
cancer medicines. For additional information, visit
http://www.ariad.com or follow ARIAD on Twitter (@ARIADPharm).
Forward-Looking StatementsThis press release contains
forward-looking statements, each of which are qualified in their
entirety by this cautionary statement. Any statements contained
herein which do not describe historical facts, including, but not
limited to the statements related to the potential therapeutic
benefits of brigatinib and the potential promise of ARIAD’s
research platform, are forward-looking statements that are based on
management’s expectations and are subject to certain factors, risks
and uncertainties that may cause actual results, outcome of events,
timing and performance to differ materially from those expressed or
implied by such statements. These factors, risks and uncertainties
include, but are not limited to, our ability to successfully
commercialize and generate profits from sales of our products; our
ability to meet anticipated clinical trial commencement, enrollment
and completion dates and regulatory filing dates for our products
and product candidates and to move new development candidates into
the clinic; our ability to execute on our key corporate
initiatives; regulatory developments and safety issues, including
difficulties or delays in obtaining regulatory and pricing and
reimbursement approvals to market our products; competition from
alternative therapies; our reliance on the performance of
third-party manufacturers, specialty pharmacies, distributors and
other collaborators for the supply, distribution, development
and/or commercialization of our products and product candidates;
the occurrence of adverse safety events with our products and
product candidates; the costs associated with our research,
development, manufacturing, commercialization and other activities;
the conduct, timing and results of preclinical and clinical studies
of our products and product candidates, including that preclinical
data and early-stage clinical data may not be replicated in
later-stage clinical studies; the adequacy of our capital resources
and the availability of additional funding; the ability to satisfy
our contractual obligations, including under our leases,
convertible debt and royalty financing agreements; patent
protection and third-party intellectual property claims;
litigation; our operations in foreign countries with or through
third parties; risks related to key employees, markets, economic
conditions, health care reform, prices and reimbursement rates; and
other risk factors detailed in our public filings with the U.S.
Securities and Exchange Commission, including our most recent
Annual Report on Form 10-K and subsequent Quarterly Reports on Form
10-Q. Except as otherwise noted, these forward-looking statements
speak only as of the date of this press release and we undertake no
obligation to update or revise any of these statements to reflect
events or circumstances occurring after this press release. We
caution investors not to place considerable reliance on the
forward-looking statements contained in this press release.
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version on businesswire.com: http://www.businesswire.com/news/home/20161026005377/en/
ARIAD Pharmaceuticals, Inc.For InvestorsManmeet Soni,
617-503-7298Manmeet.soni@ariad.comorFor MediaLiza Heapes,
617-621-2315Liza.heapes@ariad.com
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