CAMBRIDGE, Mass. & VIENNA--(BUSINESS WIRE)--ARIAD
Pharmaceuticals, Inc. (NASDAQ: ARIA), a rare cancer-focused
innovative biotechnology company, today announced clinical data on
brigatinib, its investigational anaplastic lymphoma kinase (ALK)
inhibitor, from the pivotal ALTA trial in ALK-positive (ALK+) non-small
cell lung cancer (NSCLC) patients who had experienced disease
progression on crizotinib therapy. As of May 31, 2016, the data show
that of patients on the 180-mg regimen with a median follow-up of 11
months, 55 percent achieved confirmed objective response as assessed by
the investigator. In this arm, the median progression-free survival
(PFS) was 15.6 months in this post-crizotinib setting, by both
investigator and independent review committee (IRC) assessment.
Additionally, in this arm, 67 percent of patients with measurable brain
metastases achieved a confirmed intracranial objective response, and
intracranial PFS was 18.4 months among patients with any brain
metastases at baseline. These data will be presented today at the
International Association for the Study of Lung Cancer (IASLC) 17th
World Conference on Lung Cancer (WCLC) being held in Vienna.
“These updated ALTA trial data show that with additional follow-up,
median progression-free survival from brigatinib given post-crizotinib
is now 15.6 months, and that this is the same whether assessed by the
investigators or an independent review committee,” said D. Ross Camidge,
M.D., Ph.D., director of thoracic oncology at the University of
Colorado. “Whether this is a reflection of broader suppression of
potential resistance mutations, or its effects on protecting the central
nervous system, or both, requires further investigation but by itself
these progression-free survival data should be very encouraging for
physicians and patients alike. These data really support the idea to
pursue brigatinib, not just post-crizotinib, but also in the ongoing
ALTA 1L study, which aims to assess its potential in the ALK-treatment
The ALTA Trial
The ALTA (ALK in Lung Cancer Trial of AP26113) trial enrolled 222
patients with ALK+ NSCLC who had been treated with and experienced
disease progression on their most recent crizotinib therapy. Patients
were randomized one-to-one to receive either 90 mg of brigatinib once
per day (QD) (Arm A), or 180 mg QD, preceded by a lead-in dose of 90 mg
QD for seven days (Arm B). In addition, patients were stratified by
presence of brain metastases at baseline and best response to prior
The primary endpoint of the ALTA trial is investigator-assessed
confirmed objective response rate (ORR) as measured by the Response
Evaluation Criteria in Solid Tumors (RECIST). Key secondary endpoints
include PFS, confirmed ORR assessed by an IRC, overall survival (OS),
CNS response and PFS, duration of response, safety and tolerability.
Key Data from the ALTA Trial Update
Brigatinib Efficacy and Safety in ALK+ NSCLC Patients:
Data as of May 31, 2016 with IRC Data as of July 13, 2016
A total of 222 patients with ALK+ NSCLC treated with prior crizotinib
therapy were randomized in the study (110 patients in Arm B at the
180-mg dose level with a seven-day lead-in at 90 mg and 112 patients
in Arm A at the 90-mg dose level). The last patient was enrolled in
the study in September 2015.
The median follow-up was 11 months in Arm B and 10.2 months in Arm A.
ALTA trial data presented at the 2016 American Society of Clinical
Oncology (ASCO) meeting, as of February 29, 2016, had median follow-up
of 8.3 months in Arm B and 7.8 months in Arm A.
Investigator-assessed confirmed ORR in Arm B was 55 percent.
IRC-assessed confirmed ORR in Arm B was 54 percent.
Investigator-assessed confirmed ORR in Arm A was 45 percent.
IRC-assessed confirmed ORR in Arm A was 49 percent.
In a subgroup analysis of confirmed ORR by baseline
characteristics, there was no difference in confirmed ORR based on
prior chemotherapy versus no prior chemotherapy.
The subgroup analysis by best response to prior crizotinib
(partial or complete response versus other) suggests that patients
who had achieved partial or complete responses on prior crizotinib
treatment had a significantly higher confirmed ORR, compared with
patients who did not achieve these responses.
Responses in Arm B included a confirmed partial response in a patient
with the ALK kinase domain G1202R mutation at baseline, which is
associated with resistance to all approved tyrosine kinase inhibitors
Median PFS was 15.6 months by both investigator assessment and IRC
assessment in Arm B. Median PFS was 8.8 months by investigator
assessment and 9.2 months by IRC assessment in Arm A.
Probability of OS at one year was 82 percent and 71 percent in Arm B
and Arm A, respectively. The median OS had not been reached in either
Of the 44 patients with measurable intracranial brain metastases at
baseline, the IRC-assessed intracranial ORR was 67 percent (12/18) in
Arm B and 46 percent (12/26) in Arm A.
The median IRC-assessed intracranial PFS was 18.4 months in Arm B
and 15.6 months in Arm A.
The most common treatment-emergent adverse events (TEAEs; = 30% of all
patients, [Arm B/A]), regardless of relationship to treatment, were
nausea (43%/36%), diarrhea (39%/21%), cough (36%/23%), headache
(30%/28%) and increased blood creatine phosphokinase (CPK) (33%/11%).
TEAEs, grade =3, occurring in =4 percent of all patients (excluding
neoplasm progression; Arm B/A), were increased CPK (10%/3%),
hypertension (6%/6%), pneumonia (5%/3%) and increased lipase (3%/5%).
A subset of pulmonary adverse events (AEs) with early onset (median:
Day 2; range: Day 1-9) occurred in six percent of all patients (grade
=3 in 3% of patients); no such events with early onset occurred after
dose escalation to 180 mg QD in Arm B.
Discontinuations and dose reductions due to AEs (Arm B/A) were 10
percent/three percent and 23 percent/eight percent, respectively.
Discontinuations due to documented progressive disease (Arm B/A) were
23 percent and 30 percent.
“We are encouraged by the maturing efficacy and safety profile of
brigatinib in this later data cut, which adds three months of follow up
compared to the data presented at ASCO,” stated Timothy P. Clackson,
Ph.D., president of research and development and chief scientific
officer at ARIAD. “These data are intended to be submitted to the
European Medicines Agency in early 2017 for marketing approval. Pending
regulatory review, we expect that brigatinib may become an important
therapeutic option for the crizotinib-resistant population.”
The poster presentation, “Brigatinib in Crizotinib-Refractory ALK+
NSCLC: Central Assessment and Updates from ALTA, a Pivotal Randomized
Phase 2 Trial,” (Abstract #4046, Poster ID P3.02a-013) will be presented
today, Wednesday, December 7, 2016 from 14:30 - 15:45 GMT.
Brigatinib is an investigational, targeted cancer medicine discovered
internally at ARIAD. 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. The FDA has
accepted brigatinib’s New Drug Application and has granted ARIAD’s
request for Priority Review and set an action date of April 29,
2017 under the Prescription Drug User Fee Act (PDUFA). ARIAD intends to
submit a Marketing Authorization Application (MAA) for brigatinib to the
European Medicines Agency (EMA) in early 2017.
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.
Investor and Analyst Briefing and Webcast
Timothy P. Clackson, Ph.D., president of research and development and
chief scientific officer of ARIAD will host an investor and analyst
briefing today, Wednesday, December 7, at 4:00 p.m. Central European
Time (10:00 a.m. Eastern Time) to discuss the data presented at WCLC.
Dr. Clackson will be joined by Karen Reckamp, MD, associate professor in
the Department of Medical Oncology & Therapeutics Research and
co-director of the Lung Cancer and Thoracic Oncology Program at City of
Hope Comprehensive Cancer Center (COHCCC).
The live webcast can be accessed by visiting the investor relations
section of the Company’s website at http://investor.ariad.com.
The call can be accessed by dialing 844-249-9386 (domestic) or
270-823-1534 (international) five minutes prior to the start time and
providing the pass code 20888507. A replay of the call will be available
on the ARIAD website approximately two hours after completion of the
call and will be archived for three weeks.
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).
This 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
promise and importance of brigatinib as a potential treatment option for
ALK+ lung cancer patients, additional clinical data that may be reported
on brigatinib and the expected timing and actions on our regulatory
filings for brigatinib, 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 and
government investigations; 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.