ARIAD Announces Phase 1/2 Trial Data on Brigatinib Published

ARIAD Pharmaceuticals, Inc. (NASDAQ: ARIA) today announced clinical data on its investigational anaplastic lymphoma kinase (ALK) inhibitor, brigatinib, were published in The Lancet Oncology (Gettinger, S.; ed al. The Lancet Onc. 2016, DOI: 10.1016/S1470-2045(16)30392-8 Published 8 November 2016). ARIAD has submitted a New Drug Application (NDA) for brigatinib to the U.S. Food and Drug Administration (FDA), seeking U.S. marketing approval for patients with metastatic ALK-positive (ALK+) non-small cell lung cancer (NSCLC) who are resistant or intolerant to crizotinib.
“The publication reports the results of the first clinical evaluation of
brigatinib in patients with advanced malignancies, including ALK+
NSCLC,” stated Scott N. Gettinger, M.D., associate professor of medicine
at Yale Cancer Center and lead author. “Brigatinib yielded responses in
the majority of patients with crizotinib-treated ALK+ NSCLC, with median
progression free survival of over one year. Additionally, responses in
the brain were achieved in this crizotinib refractory population. Early
onset pulmonary adverse events, which occurred in eight percent of
patients, generally within 48 hours of first dose, appeared to be
related to starting dose.”
The data published this week include safety analyses on all patients in
the trial (N=137) and efficacy analyses on all patients with ALK+ NSCLC
(n=79). Of the 79 ALK+ NSCLC patients, all but eight had previously been
treated with crizotinib. With patient data as of June 2015, the median
time on treatment for ALK+ NSCLC patients was 15.4 months (range, 0.03 –
39.4 months, ongoing).
The confirmed objective response rate (ORR) was 62% (44/71) in ALK+
NSCLC patients with prior crizotinib treatment. The median progression
free survival (PFS) of ALK+ NSCLC patients previously treated with
crizotinib was 13.2 months. Eight ALK+ NSCLC patients in the trial were
crizotinib-naive. Of these, all eight achieved a confirmed objective
response, including three complete responses. At the time of analysis,
median PFS was not reached in these patients. Brain metastases were
identified in 63% of ALK+ NSCLC patients (50/79) at baseline. The
intracranial ORR was 53% (8/15) among evaluable patients with measurable
brain metastases.
The most common grade 3–4 treatment-emergent adverse events across all
doses were increased lipase (9%; 12/137), dyspnea (6%; 8/137), and
hypertension (5%; 7/137). Serious treatment-emergent adverse events
(excluding neoplasm progression) reported in ≥5% of all patients were
dyspnea (7%; 10/137), pneumonia (7%; 9/137), and hypoxia (5%; 7/137).
Eight percent of patients (11/137) experienced a subset of pulmonary
adverse events with early onset, most occurring within 48 hours of
dosing. The frequency of these events appeared dose-related. Among
patients who started at 90 mg once daily and continued at this dose or
escalated to 180 mg once daily after seven days, 2% (1/50) had such
events.
Data from the Phase 1/2 trial and pivotal ALTA trial of brigatinib have
been included in the NDA submitted to the FDA. The FDA has granted
ARIAD’s request for Priority Review and has set an action date of April
29, 2017 under the Prescription Drug User Fee Act (PDUFA). ARIAD is
seeking accelerated U.S. marketing approval for brigatinib in patients
with metastatic ALK+ NSCLC who are resistant or intolerant to crizotinib
and plans to submit a Marketing Authorization Application (MAA) for
brigatinib to the European Medicines Agency (EMA) in early 2017.
“This in-depth publication provides a thorough review of the Phase 1/2
trial of brigatinib, ARIAD’s internally developed targeted cancer
candidate under regulatory review,” stated Timothy P. Clackson, Ph.D.,
president of research and development and chief scientific officer at
ARIAD. “We are excited to continue to work with academic collaborators
to provide additional clinical detail on the brigatinib trials,
including upcoming presentations at the World Conference on Lung Cancer
in December.”
About Brigatinib
Brigatinib is an investigational, targeted cancer medicine discovered
internally at ARIAD. It is in development for the treatment of patients
with anaplastic lymphoma kinase positive (ALK+) non-small cell lung
cancer (NSCLC). The global Phase 2 ALTA trial, in patients with locally
advanced or metastatic ALK+ NSCLC who were previously treated with
crizotinib, is the primary basis for brigatinib’s 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.
Brigatinib received Breakthrough Therapy designation from the FDA for
the treatment of patients with ALK+ NSCLC whose tumors are resistant to
crizotinib, and was granted orphan drug designation by the FDA for the
treatment of ALK+ NSCLC.
About ALK+ NSCLC
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. Approximately three to eight percent of patients with NSCLC have a
rearrangement in the ALK gene.
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 https://www.ariad.com
or follow ARIAD on Twitter (@ARIADPharm).
Forward-Looking Statements
This press release contains forward-looking statements. Any statements
contained herein which do not describe historical facts, including, but
not limited to, statements regarding: regulatory filings for brigatinib
and the therapeutic potential of brigatinib are forward-looking
statements which 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, among others: early-stage clinical data may
not be replicated in later-stage clinical studies; the costs associated
with our research, development, manufacturing and other activities; the
adequacy of our capital resources and the availability of additional
funding; our ongoing and additional clinical trials of brigatinib may
not be successful or initiated, enrolled or conducted in a timely
manner; our ability to meet anticipated regulatory filing and approval
dates for brigatinib; regulatory developments and safety issues,
including difficulties or delays in obtaining regulatory and pricing and
reimbursement approvals for brigatinib; competitive risks; manufacturing
issues and those additional 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. All forward‐looking statements in this
press release are qualified in their entirety by this cautionary
statement.