UNITED
STATES
SECURITIES
AND EXCHANGE COMMISSION
Washington,
D.C. 20549
FORM
8-K
CURRENT
REPORT
Pursuant
to Section 13 or 15(d) of The Securities Exchange Act of 1934
Date
of Report (Date of earliest event reported): January
6, 2015
ARIAD
Pharmaceuticals, Inc.
(Exact
name of registrant as specified in its charter)
Delaware
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001-36172
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22-3106987
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(State
or other jurisdiction
of
incorporation)
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(Commission
File
Number)
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(I.R.S.
Employer
Identification
No.)
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26 Landsdowne Street, Cambridge, Massachusetts
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02139
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(Address of principal executive offices)
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(Zip Code)
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Registrant's telephone number, including
area code: (617) 494-0400
Not
Applicable
(Former
name or former address, if changed since last report)
Check the
appropriate box below if the Form 8-K filing is intended to
simultaneously satisfy the filing obligation of the registrant under any
of the following provisions (see General Instruction A.2.
below):
⃞
Written
communications pursuant to Rule 425 under the Securities Act (17 CFR
230.425)
⃞
Soliciting
material pursuant to Rule 14a-12 under the Exchange Act (17 CFR
240.14a-12)
⃞
Pre-commencement
communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR
240.14d-2(b))
⃞
Pre-commencement
communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR
240.13e-4(c))
On January 6, 2015, ARIAD Pharmaceuticals, Inc. (the “Company”) issued a
press release announcing that it has concluded consultations with U.S.
and European health authorities regarding the design of a randomized,
dose-ranging trial to evaluate three starting doses of Iclusig®
(ponatinib) in patients with refractory, chronic-phase chronic myeloid
leukemia (CP-CML). The trial is expected to inform the optimal use of
Iclusig in these patients and will begin by mid-2015. Approximately 450
patients will be enrolled at clinical sites around the world.
This study will enroll patients with CP-CML who are resistant to at
least two approved tyrosine kinase inhibitors. These patients will be
randomized equally to receive once-daily administration of 45 mg (cohort
A), 30 mg (cohort B) or 15 mg (cohort C) of Iclusig. Patients in cohorts
A and B will have their daily dose reduced to 15 mg upon achievement of
major cytogenetic response (MCyR). The primary endpoint of the trial is
MCyR by 12 months for each cohort. Secondary endpoints include rate of
vascular occlusive events in each dose cohort, rates of adverse events
and rates of serious adverse events. Other secondary endpoints include
cytogenetic, molecular and hematologic response rates, tolerability,
duration of response, time to response, disease control rate,
progression-free survival and overall survival.
A copy of the press release is being filed herewith as Exhibit 99.1 and
is incorporated by reference herein.
ITEM 9.01
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Financial Statements and Exhibits
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(d) The following exhibit is filed with this report:
Exhibit Number
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Description
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99.1
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Press Release dated January 6, 2015.
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The press release contains hypertext links to information on our
websites. The information on our websites is not incorporated by
reference into this Current Report on Form 8-K and does not constitute a
part of this Form 8-K.
Pursuant to the requirements of the Securities Exchange Act of 1934, the
registrant has duly caused this report to be signed on its behalf by the
undersigned hereunto duly authorized.
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ARIAD Pharmaceuticals, Inc.
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By:
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/s/ Edward M. Fitzgerald
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Edward M. Fitzgerald
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Executive Vice President, Chief Financial Officer
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Date:
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January 7, 2015
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3
Exhibit 99.1
ARIAD
Announces Phase 2 Dose-Ranging Trial of Iclusig (Ponatinib) to Begin by
Mid-2015
Randomized
Global Trial to Evaluate Safety and Efficacy of Iclusig at Three
Starting Doses
CAMBRIDGE, Mass.--(BUSINESS WIRE)--January 6, 2015--ARIAD
Pharmaceuticals, Inc. (NASDAQ: ARIA) today announced that it has
concluded consultations with U.S. and European health authorities
regarding the design of a randomized, dose-ranging trial to evaluate
three starting doses of Iclusig® (ponatinib) in patients
with refractory, chronic-phase chronic myeloid leukemia (CP-CML). The
trial is expected to inform the optimal use of Iclusig in these patients
and will begin by mid-2015. Approximately 450 patients will be enrolled
at clinical sites around the world.
“This clinical trial is expected to provide important data regarding the
efficacy of Iclusig treatment initiating at doses less than the
currently approved starting dose and maintaining patients on a lower
dose. We expect that this will better characterize the safety profile of
Iclusig beginning at lower doses,” said Frank G. Haluska, M.D., Ph.D.,
senior vice president of clinical research and development and chief
medical officer at ARIAD. “We also anticipate that this trial will give
us the opportunity to further explore strategies for dose reductions
after patients have achieved a major cytogenetic response in order to
maximize an individual’s benefit/risk while on therapy.”
Major Design Features of the Trial
This study will enroll patients with CP-CML who are resistant to at
least two approved tyrosine kinase inhibitors. These patients will be
randomized equally to receive once-daily administration of 45 mg (cohort
A), 30 mg (cohort B) or 15 mg (cohort C) of Iclusig. Patients in cohorts
A and B will have their daily dose reduced to 15 mg upon achievement of
major cytogenetic response (MCyR).
The primary endpoint of the trial is MCyR by 12 months for each cohort.
Secondary endpoints include rate of vascular occlusive events in each
dose cohort, rates of adverse events and rates of serious adverse
events. Other secondary endpoints include cytogenetic, molecular and
hematologic response rates, tolerability, duration of response, time to
response, disease control rate, progression-free survival and overall
survival.
Interim reports will be submitted to the U.S. Food and Drug
Administration and the European Medicines Agency, providing an
opportunity to review safety and efficacy data collected during the
trial. Patients will be enrolled at up to 90 cancer centers globally.
For more information about the trial, patients and physicians should
call the U.S. toll-free number 855-552-7423, the EU toll-free number 800
00027423, or the international number +1 617-503-7423, or email ARIAD at ClinicalTrials@ariad.com.
About Iclusig® (ponatinib) tablets
Iclusig is approved in the U.S., EU, Australia and Switzerland.
In the U.S., Iclusig is a kinase inhibitor indicated for the:
-
Treatment of adult patients with T315I-positive chronic myeloid
leukemia (chronic phase, accelerated phase, or blast phase) or
T315I-positive Philadelphia chromosome positive acute lymphoblastic
leukemia (Ph+ ALL).
-
Treatment of adult patients with chronic phase, accelerated phase, or
blast phase chronic myeloid leukemia or Ph+ ALL for whom no other
tyrosine kinase inhibitor (TKI) therapy is indicated.
IMPORTANT SAFETY INFORMATION, INCLUDING THE BOXED WARNING
WARNING: VASCULAR OCCLUSION, HEART FAILURE, and HEPATOTOXICITY
See full prescribing information for complete boxed warning
-
Vascular Occlusion: Arterial and venous thrombosis and occlusions
have occurred in at least 27% of Iclusig treated patients, including
fatal myocardial infarction, stroke, stenosis of large arterial
vessels of the brain, severe peripheral vascular disease, and the need
for urgent revascularization procedures. Patients with and without
cardiovascular risk factors, including patients less than 50 years
old, experienced these events. Monitor for evidence of thromboembolism
and vascular occlusion. Interrupt or stop Iclusig immediately for
vascular occlusion. A benefit risk consideration should guide a
decision to restart Iclusig therapy.
-
Heart Failure, including fatalities, occurred in 8% of
Iclusig-treated patients. Monitor cardiac function. Interrupt or stop
Iclusig for new or worsening heart failure.
-
Hepatotoxicity, liver failure and death have occurred in
Iclusig-treated patients. Monitor hepatic function. Interrupt Iclusig
if hepatotoxicity is suspected.
Vascular Occlusion: Arterial and venous thrombosis and
occlusions, including fatal myocardial infarction, stroke, stenosis of
large arterial vessels of the brain, severe peripheral vascular disease,
and the need for urgent revascularization procedures have occurred in at
least 27% of Iclusig-treated patients from the phase 1 and phase 2
trials. Iclusig can also cause recurrent or multi-site vascular
occlusion. Overall, 20% of Iclusig-treated patients experienced an
arterial occlusion and thrombosis event of any grade. Fatal and
life-threatening vascular occlusion has occurred within 2 weeks of
starting Iclusig treatment and in patients treated with average daily
dose intensities as low as 15 mg per day. The median time to onset of
the first vascular occlusion event was 5 months. Patients with and
without cardiovascular risk factors have experienced vascular occlusion
although these events were more frequent with increasing age and in
patients with prior history of ischemia, hypertension, diabetes, or
hyperlipidemia. Interrupt or stop Iclusig immediately in patients who
develop vascular occlusion events.
Heart Failure: Fatal and serious heart failure or left
ventricular dysfunction occurred in 5% of Iclusig-treated patients
(22/449). Eight percent of patients (35/449) experienced any grade of
heart failure or left ventricular dysfunction. Monitor patients for
signs or symptoms consistent with heart failure and treat as clinically
indicated, including interruption of Iclusig. Consider discontinuation
of Iclusig in patients who develop serious heart failure.
Hepatotoxicity: Iclusig can cause hepatotoxicity, including liver
failure and death. Fulminant hepatic failure leading to death occurred
in an Iclusig-treated patient within one week of starting Iclusig. Two
additional fatal cases of acute liver failure also occurred. The fatal
cases occurred in patients with blast phase CML (BP-CML) or Philadelphia
chromosome positive acute lymphoblastic leukemia (Ph+ ALL). Severe
hepatotoxicity occurred in all disease cohorts. Iclusig treatment may
result in elevation in ALT, AST, or both. Monitor liver function tests
at baseline, then at least monthly or as clinically indicated.
Interrupt, reduce or discontinue Iclusig as clinically indicated.
Hypertension: 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). Eight patients treated with
Iclusig (2%) experienced treatment-emergent symptomatic hypertension as
a serious adverse reaction, including one patient (<1%) with
hypertensive crisis. Patients may require urgent clinical intervention
for hypertension associated with confusion, headache, chest pain, or
shortness of breath. In 131 patients with Stage 1 hypertension at
baseline, 61% (80/131) developed Stage 2 hypertension. Monitor and
manage blood pressure elevations during Iclusig use and treat
hypertension to normalize blood pressure. Interrupt, dose reduce, or
stop Iclusig if hypertension is not medically controlled.
Pancreatitis: Clinical pancreatitis occurred in 6% (28/449) of
patients (5% Grade 3) treated with Iclusig. Pancreatitis resulted in
discontinuation or treatment interruption in 6% of patients (25/449).
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. Consider additional serum lipase
monitoring in patients with a history of pancreatitis or alcohol abuse.
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 pancreatitis. Do not consider
restarting Iclusig until patients have complete resolution of symptoms
and lipase levels are less than 1.5 x ULN.
Neuropathy: Peripheral and cranial neuropathy have occurred in
Iclusig-treated patients. Overall, 13% (59/449) of Iclusig-treated
patients experienced a peripheral neuropathy event of any grade (2%,
grade 3/4). In clinical trials, the most common peripheral neuropathies
reported were peripheral neuropathy (4%, 18/449), paresthesia (4%,
17/449), hypoesthesia (2%, 11/449), and hyperesthesia (1%, 5/449).
Cranial neuropathy developed in 1% (6/449) of Iclusig-treated patients
(<1% grade 3/4). Of the patients who developed neuropathy, 31% (20/65)
developed neuropathy during the first month of treatment. Monitor
patients for symptoms of neuropathy, such as hypoesthesia,
hyperesthesia, paresthesia, discomfort, a burning sensation, neuropathic
pain or weakness. Consider interrupting Iclusig and evaluate if
neuropathy is suspected.
Ocular Toxicity: Serious ocular toxicities leading to blindness
or blurred vision have occurred in Iclusig-treated patients. Retinal
toxicities including macular edema, retinal vein occlusion, and retinal
hemorrhage occurred in 3% of Iclusig-treated patients. Conjunctival or
corneal irritation, dry eye, or eye pain occurred in 13% of patients.
Visual blurring occurred in 6% of the patients. Other ocular toxicities
include cataracts, glaucoma, iritis, iridocyclitis, and ulcerative
keratitis. Conduct comprehensive eye exams at baseline and periodically
during treatment.
Hemorrhage: Serious bleeding events, including fatalities,
occurred in 5% (22/449) of patients treated with Iclusig. Hemorrhagic
events occurred in 24% of patients. The incidence of serious bleeding
events was higher in patients with accelerated phase CML (AP-CML),
BP-CML, and Ph+ ALL. Most hemorrhagic events, but not all occurred in
patients with grade 4 thrombocytopenia. Interrupt Iclusig for serious or
severe hemorrhage and evaluate.
Fluid Retention: Serious fluid retention events occurred in 3%
(13/449) of patients treated with Iclusig. One instance of brain edema
was fatal. In total, fluid retention occurred in 23% of the patients.
The most common fluid retention events were peripheral edema (16%),
pleural effusion (7%), and pericardial effusion (3%). 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 1% (3/449) of
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% (25/449) 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).
Interrupt Iclusig and evaluate.
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). Due to the potential for
tumor lysis syndrome in patients with advanced disease, 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.
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 U.S. Prescribing Information for Iclusig,
including the Boxed Warning, for additional important safety information.
About ARIAD
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.com or
follow ARIAD on Twitter (@ARIADPharm).
This press release contains “forward-looking statements” including, but
not limited to, statements relating to an upcoming dose-ranging study
for ponatinib and its potential to further explore dose reduction
strategies after patients have achieved a major cytogenetic response.
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 enrollment,
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.
Iclusig® is a registered trademark of ARIAD
Pharmaceuticals, Inc.
CONTACT:
ARIAD Pharmaceuticals
For Investors
Kendra
Adams, 617-503-7028
Kendra.adams@ariad.com
or
For
Media
Liza Heapes, 617-620-4888
Liza.heapes@ariad.com
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