ARIAD Announces Long-Term Durability-of-Response Data on Ponatinib from
Ongoing Phase 1 Study
Median follow-up of more than three years for chronic-phase CML patients
72 percent of patients maintain major cytogenetic response; median duration
not yet reached
2013 ASCO Annual Meeting
CHICAGO & CAMBRIDGE, Mass. -- June 2, 2013
ARIAD Pharmaceuticals, Inc. (NASDAQ: ARIA) today announced long-term
durability-of-response data from its Phase 1 trial of Iclusig^® (ponatinib) in
heavily pretreated patients with resistant or intolerant chronic myeloid
leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic
leukemia (Ph+ ALL). The study shows that among chronic-phase (CP) patients,
the median durations of major and complete cytogenetic responses, along with
major molecular response, have yet to be reached. The median follow-up for CP
patients still on study is now more than three years (36.5 months).
These data are being featured today at 8:00 a.m. CT in a poster presentation
at the Annual Meeting of the American Society of Clinical Oncology (ASCO)
being held in Chicago.
“These data show that ponatinib continues to provide deep, durable clinical
responses in chronic-phase CML patients who failed several prior tyrosine
kinase inhibitor therapies,” stated Michael Mauro, M.D., associate professor
at the Oregon Health & Science University, Portland, Oregon. “It is noteworthy
that these patients are maintaining their responses over this long period of
time and that a median duration of response to ponatinib has not yet been
Phase 1 Long-Term Update
The Phase 1 dose-escalation study of ponatinib enrolled 81 patients with
resistant or refractory hematologic cancers, including 43 patients with
chronic-phase CML. Sixty-one percent of the CP-CML patients in this study had
failed at least three prior tyrosine kinase inhibitors (TKI).
The trial is ongoing, and study data reported at ASCO show deep and durable
anti-leukemic activity in CP-CML patients.
*With a median follow-up of 36.5 months, 28 of the 43 patients with CP-CML
remain on study (65%). Of these, 23 are currently in major cytogenetic
response (MCyR), 22 in complete cytogenetic response (CCyR), and 17 in
major molecular response (MMR) or greater.
*The median time to MCyR among responders was 2.8 months (range, 1.8 to
16.6 months). The duration of MCyR ranged from 1.9 to more than 46.5
months (ongoing); the median has not yet been reached.
*The median time to CCyR among responders was 5.5 months (range, 1.8 to
33.2 months). The duration of CCyR ranged from 1.9 to more than 40.5
months (ongoing); the median has not yet been reached.
*The median time to MMR was 5.6 months (range, 1.8 to 38.7 months). The
duration of MMR ranged from 2.8 to more than 41 months (ongoing); the
median has not yet been reached. Of the 17 patients remaining on trial in
MMR, 7 have achieved the deeper response landmark of MR4 and an additional
6 have achieved MR4.5.
*The most common non-hematologic treatment-related adverse events among all
patients in this trial included rash (42%), arthralgia (20%), increased
lipase (20%), fatigue (20%) and dry skin (19%), with the majority of these
being grades 1 or 2 in severity. The most common hematologic
treatment-related adverse events included thrombocytopenia (34%),
neutropenia (14%) and anemia (12%), with thrombocytopenia and neutropenia
being primarily grades 3 or 4 in severity.
“In addition to ponatinib achieving robust patient responses in this
refractory CML population, responses are deepening over time, with nearly all
responding patients in CCyR and more than half of the responders showing deep
molecular responses,” stated Frank G. Haluska, M.D., Ph.D., senior vice
president and chief medical officer at ARIAD.
About CML and Ph+ ALL
CML 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.
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, a common
mutation which has been associated with resistance to other approved TKIs.
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
Important Safety Information
Arterial Thrombosis: Cardiovascular, cerebrovascular, and peripheral vascular
thrombosis, including fatal myocardial infarction and stroke have occurred in
Iclusig-treated patients. In clinical trials, serious arterial thrombosis
occurred in 8% of Iclusig-treated patients. Interrupt and consider
discontinuation of Iclusig in patients who develop arterial thrombotic events.
Hepatotoxicity: Hepatotoxicity, liver failure and death have occurred in
Iclusig-treated patients. Monitor hepatic function prior to and during
treatment. Interrupt and then reduce or discontinue Iclusig for
Warnings and Precautions
Congestive Heart Failure: Twenty patients treated with Iclusig (4%)
experienced serious congestive heart failure (CHF) or left ventricular
dysfunction (LVD), with 4 fatalities. Thirty-three patients treated with
Iclusig (7%) experienced any grade of CHF or LVD. Monitor patients for signs
or symptoms consistent with CHF and treat as clinically indicated, including
interruption of Iclusig. Consider discontinuation of Iclusig in patients who
develop serious CHF.
Hypertension: Eight patients treated with Iclusig (2%) experienced
treatment-emergent symptomatic hypertension as a serious adverse reaction,
including hypertensive crisis. Treatment-emergent hypertension (defined as
systolic BP≥140 mm Hg or diastolic BP≥90 mm Hg on at least one occasion)
occurred in 67% of patients (300/449). Monitor and manage blood pressure
Pancreatitis: 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. Dose interruption or reduction may be
required. In cases where lipase elevations are accompanied by abdominal
symptoms, interrupt treatment with Iclusig and evaluate patients for
Hemorrhage: Serious bleeding events occurred in 5% (22/449) of patients
treated with Iclusig, including fatalities. Hemorrhagic events occurred in 24%
of patients. The incidence of serious bleeding events 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 or severe hemorrhage.
Fluid Retention: 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.
Cardiac Arrhythmias: 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 and occurred in 20 patients. For 13 patients,
the event led to hospitalization. Advise patients to report signs and symptoms
of rapid heart rate (palpitations, dizziness).
Myelosuppression: Severe (Grade 3 or 4) myelosuppression occurred in 48%
(215/449) of patients treated with Iclusig. The incidence of these events was
greater in patients with AP-CML, BP-CML and Ph+ ALL than in patients with
CP-CML. 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.
Tumor Lysis Syndrome: Two patients (<1%) with advanced disease (AP-CML,
BP-CML, or Ph+ ALL) treated with Iclusig developed serious tumor lysis
syndrome. Hyperuricemia occurred in 7%(30/449) of patients overall; the
majority had CP-CML (19 patients). Ensure adequate hydration and treat high
uric acid levels prior to initiating therapy with Iclusig.
Compromised Wound Healing and Gastrointestinal Perforation: 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 post-cholecystectomy.
Embryo-Fetal Toxicity: Iclusig can cause fetal harm. If Iclusig is used during
pregnancy, or if the patient becomes pregnant while taking Iclusig, the
patient should be apprised of the potential hazard to the fetus. Advise women
to avoid pregnancy while taking Iclusig.
The most common non-hematologic adverse reactions (≥20%) were hypertension,
rash, abdominal pain, fatigue, headache, dry skin, constipation, arthralgia,
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.
ARIAD Pharmaceuticals, Inc., headquartered in Cambridge, Massachusetts and
Lausanne, Switzerland, is an integrated global oncology company focused on
transforming the lives of cancer patients with breakthrough medicines. ARIAD
is working on new medicines to advance the treatment of various forms of
chronic and acute leukemia, lung cancer and other difficult-to-treat 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.comor follow ARIAD on
This press release contains “forward-looking statements” including, but not
limited to, statements relating to the updated clinical data and durability of
response for ponatinib. 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.
ARIAD Pharmaceuticals, Inc.
Kendra Adams, 617-503-7028
Liza Heapes, 617-621-2315
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