|[December 14, 2012]
ARIAD Announces Accelerated Approval by FDA of Iclusig (Ponatinib) for Patients with CML and Ph+ ALL Resistant or Intolerant to Prior Tyrosine Kinase Inhibitor Therapy
CAMBRIDGE, Mass. --(Business Wire)--
Pharmaceuticals, Inc. (NASDAQ: ARIA) today announced that following
a priority review, the U.S. Food and Drug Administration (FDA) has
granted accelerated approval of Iclusig™ (ponatinib) for the treatment
of adult patients with chronic, accelerated or blast phase chronic
myeloid leukemia (CML) that is resistant or intolerant to prior tyrosine
kinase inhibitor (TKI) therapy or Philadelphia chromosome-positive acute
lymphoblastic leukemia (Ph+ ALL) that is resistant or intolerant to
prior TKI therapy.
The Iclusig™ bottle (Photo: Business Wire)
"Today's FDA approval of Iclusig is an important advance in the
treatment of patients with CML and Ph+ ALL who are resistant or
intolerant to prior TKI therapy," stated Harvey J. Berger, M.D.,
chairman and chief executive officer of ARIAD. "Within less than five
years, we were able to bring Iclusig from the start of clinical
development to U.S. approval, achieving a major milestone in ARIAD's
history. We have now transformed ARIAD into a commercial oncology
company addressing major unmet medical needs for cancer patients."
Approximately 5,000 new cases of CML are diagnosed each year in the U.S.
CML patients treated with TKIs can develop resistance or intolerance
over time to these therapies. Iclusig is a targeted cancer medicine
discovered and developed at ARIAD. It was designed by ARIAD scientists
using ARIAD's platform of computational chemistry and structure-based
drug design to inhibit BCR-ABL, including drug-resistant mutants that
arise during treatment. Iclusig is the only TKI that demonstrates
activity against the T315I gatekeeper mutation of BCR-ABL, the most
common mutation occurring in approximately ten percent of patients with
"The availability of Iclusig will improve the outcome of many patients
with CML and Philadelphia-positive ALL who are resistant or intolerant
to prior TKI therapy. It is an effective therapy that meets an unmet
medical need and has to date overcome all known resistant mutations in
preclinical studies," said Jorge Cortes, M.D., professor and deputy
chair, Department of Leukemia, The University of Texas M.D. Anderson
Cancer Center, Houston, TX. "Clinical responses to Iclusig have been
observed in patients regardless of their mutation status or stage of
disease. It is a valuable new treatment option for leukemia patients."
"For patients with CML and Philadelphia-positive ALL who become
resistant or intolerant to TKI treatments, the approval of Iclusig is
very positive news," said Rosalie Canosa, program division director at
CancerCare. "The addition of Iclusig to the arsenal of anti-leukemia
medicines is a significant development and one that offers hope for
patients coping with CML and Philadelphia-positive ALL."
The FDA approval of Iclusig was based on results from the pivotal Phase
2 PACE (Ponatinib Ph+ ALL and CML Evaluation) trial in patients with CML
or Ph+ ALL who were resistant or intolerant to prior TKI therapy, or who
had the T315I mutation of BCR-ABL. Iclusig had robust anti-leukemic
activity, with 54 percent of chronic-phase CML patients, including 70
percent of patients with the T315I mutation, achieving a major
cytogenetic response (MCyR) - the primary endpoint of the PACE trial for
In patients with advanced disease, 52 percent of accelerated-phase CML
patients, 31 percent of blast-phase CML patients and 41 percent of Ph+
ALL patients achieved a major hematologic response (MaHR) to Iclusig.
MaHR was the primary endpoint in the trial for patients with advanced
ARIAD PASS™ Patient Access and Support Services
Iclusig will be available to patients in the United States within
approximately two weeks through a number of select specialty pharmacies.
The Company has established the ARIAD PASS™ (Patient Access and Support
Services) program, a comprehensive support system designed to help
patients access, afford and adhere to treatment with Iclusig, including
patients without insurance or who are underinsured. ARIAD PASS offers
coverage support, including benefits verification and financial
assistance through dedicated benefits coordinators. The program also
includes ARIAD PASS Nurses who provide treatment support for patients
Healthcare professionals or patients can access information about ARIAD
PASS by calling 1-855-447-PASS (855-447-7277) or visiting www.ARIADPASS.com.
Today's Conference Call
ARIAD will hold a conference call and webcast today, December 14, at
1:30 p.m. ET to discuss the FDA approval of Iclusig, its availability,
reimbursement and paient assistance program. 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 866-831-5605 (domestic) or
617-213-8851 (international) five minutes prior to the start time and
providing the pass code 51636171. 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.
About Iclusig (ponatinib)
Iclusig is a kinase inhibitor. The primary target for Iclusig is
BCR-ABL, an abnormal tyrosine kinase that is expressed in chronic
myeloid leukemia (CML) and Philadelphia-chromosome positive acute
lymphoblastic leukemia (Ph+ ALL). Iclusig was designed using ARIAD's
computational and structure-based drug design platform specifically to
inhibit the activity of BCR-ABL. Iclusig targets not only native BCR-ABL
but also its isoforms that carry mutations that confer resistance to
treatment, including the T315I mutation, which is the most common
mutation among resistant patients. Iclusig is the only TKI that is
effective in CML and Ph+ ALL patients with this mutation.
Please see important safety information below, and the full prescribing
information for Iclusig at www.ariad.com
Indication, Usage and Dosing
Iclusig is indicated for the treatment of adult patients with chronic
phase, accelerated phase, or blast phase chronic myeloid leukemia (CML)
that is resistant or intolerant to prior tyrosine kinase inhibitor (TKI)
therapy or Philadelphia chromosome-positive acute lymphoblastic leukemia
(Ph+ ALL) that is resistant or intolerant to prior TKI therapy.
This indication is based upon response rate. There are no trials
verifying an improvement in disease-related symptoms or increased
survival with Iclusig.
The recommended dose of Iclusig is a 45 mg tablet taken once-daily with
or without food.
Important Safety Information
Cardiovascular, cerebrovascular, and peripheral vascular thrombosis,
including fatal myocardial infarction and stroke, have been observed.
Serious arterial thrombosis occurred in 8% of Iclusig-treated patients.
Patients with cardiovascular risk factors may be at increased risk for
arterial thrombosis with Iclusig. Interrupt and consider dose
modification or discontinuation of Iclusig in patients who develop
arterial thrombotic events.
Hepatotoxicity, including two cases of fatal liver failure in patients
with advanced disease, has been observed. Iclusig treatment may result
in elevation in ALT, AST, or both. Monitor liver function tests at
baseline, monthly or as clinically indicated. Interrupt, reduce or
discontinue Iclusig as clinically indicated.
Warnings and Precautions
Twenty patients treated with Iclusig (4%) experienced serious congestive
heart failure or left ventricular dysfunction, with 4 fatalities.
Monitor patients for signs or symptoms consistent with congestive heart
failure and treat as clinically indicated. Consider dose interruption
and discontinuation of Iclusig.
2% of Iclusig patients experienced treatment-emergent hypertension as a
serious adverse reaction. Treatment-emergent hypertension occurred in
67% of patients. In patients with baseline systolic blood pressure < 140
mm Hg and baseline diastolic blood pressure < 90 mm Hg, 49% developed
Stage 1 hypertension, and 29% developed Stage 2 hypertension. Monitor
and manage blood pressure elevations.
Clinical pancreatitis occurred in 6% of patients (5% Grade 3) treated
with Iclusig. The incidence of treatment emergent lipase elevation was
41%. Check serum lipase every 2 weeks for the first 2 months and then
monthly thereafter or as clinically indicated. In cases where lipase
elevations are accompanied by abdominal symptoms, evaluate patients for
pancreatitis. Dose interruption or reduction may be required.
Serious bleeding events occurred in 5% of patients treated with Iclusig,
including fatalities. The incidence was higher in patients with AP-CML,
BP-CML, and Ph+ ALL. Most events occurred in patients with grade 4
thrombocytopenia. Interrupt Iclusig for serious hemorrhagic events.
Serious fluid retention events occurred in 3% of patients treated with
Iclusig. One instance of brain edema was fatal. Monitor patients for
fluid retention and manage patients as clinically indicated. Interrupt,
reduce, or discontinue Iclusig as clinically indicated.
Symptomatic bradyarrhythmias that led to a requirement for pacemaker
implantation occurred in 3 (1%) Iclusig-treated patients. Advise
patients to report signs and symptoms suggestive of slow heart rate
(fainting, dizziness, or chest pain).
Supraventricular tachyarrhythmias occurred in 5% of Iclusig-treated
patients. Atrial fibrillation was the most common supraventricular
tachyarrhythmia. Advise patients to report signs and symptoms of rapid
heart rate (palpitations, dizziness).
Severe (Grade 3 or 4) myelosuppression occurred in 48% of patients
treated with Iclusig. Obtain complete blood counts every 2 weeks for the
first 3 months and then monthly or as clinically indicated, and adjust
the dose as recommended.
Two patients (<1%) with advanced disease (AP-CML, BP-CML, or Ph+ ALL)
developed serious tumor lysis syndrome. Hyperuricemia occurred in 7% of
patients overall. Ensure adequate hydration and treat high uric acid
levels prior to initiating therapy with Iclusig.
Since Iclusig may compromise wound healing, interrupt Iclusig for at
least 1 week prior to major surgery. Serious gastrointestinal
perforation (fistula) occurred in one patient 38 days
Iclusig can cause fetal harm. Advise women to avoid pregnancy while
The most common non-hematologic adverse reactions (=20%) were
hypertension, rash, abdominal pain, fatigue, headache, dry skin,
constipation, arthralgia, and nausea, and pyrexia. Hematologic adverse
reactions included thrombocytopenia, anemia, neutropenia, lymphopenia,
and leukopenia. Please see the full Prescribing Information for Iclusig,
including the Boxed Warning.
About CML and Ph+ ALL
is characterized by an excessive and unregulated production of white
blood cells by the bone marrow due to a genetic abnormality that
produces the BCR-ABL protein. After a chronic phase of production of too
many white blood cells, CML typically evolves to the more aggressive
phases referred to as accelerated phase and blast crisis. Ph+ ALL is a
subtype of acute lymphoblastic leukemia that carries the Ph+ chromosome
that produces BCR-ABL. It has a more aggressive course than CML and is
often treated with a combination of chemotherapy and tyrosine kinase
inhibitors. The BCR-ABL protein is expressed in both of these diseases.
ARIAD Pharmaceuticals, Inc. is a global oncology company focused on the
discovery, development and commercialization of medicines to transform
the lives of cancer patients. ARIAD's first medicine, Iclusig™, is
approved in the U.S. for the treatment of adult patients with chronic,
accelerated or blast phase chronic myeloid leukemia that is resistant or
intolerant to prior tyrosine kinase inhibitor (TKI) therapy or
Philadelphia chromosome-positive acute lymphoblastic leukemia that is
resistant or intolerant to prior TKI therapy. Additional clinical trials
of Iclusig in other cancers are ongoing. ARIAD is also studying AP26113,
another molecularly targeted medicine, in certain forms of lung cancer.
For additional information, visit http://www.ariad.com
or follow ARIAD on Twitter
This press release contains "forward-looking statements" including, but
not limited to, potential regulatory approvals, new indications or
labeling for, or potential future sales of Iclusig. Forward-looking
statements 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 risks and
uncertainties include, but are not limited to, preclinical data and
early-stage clinical data that may not be replicated in later-stage
clinical studies, the costs associated with our research, development,
manufacturing and other activities, the conduct, timing and results of
pre-clinical and clinical studies of our product candidates, the
adequacy of our capital resources and the availability of additional
funding, and other factors detailed in the Company's public filings with
the U.S. Securities and Exchange Commission. The information contained
in this press release is believed to be current as of the date of
original issue. The Company does not intend to update any of the
forward-looking statements after the date of this document to conform
these statements to actual results or to changes in the Company's
expectations, except as required by law.
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