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): December
8, 2014
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))
ITEM 8.01 Other Events.
On December 8, 2014, ARIAD Pharmaceuticals, Inc. (the “Company”) issued
the first of three press releases announcing data presented at the 56th
Annual Meeting of the American Society of Hematology (ASH) in San
Francisco. This press release detailed long-term follow up from the
pivotal Phase 2 PACE trial of Iclusig® (ponatinib), the
Company’s approved BCR-ABL inhibitor, in heavily pretreated patients
with resistant or intolerant chronic myeloid leukemia (CML) or
Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL).
The study now shows that with a median follow-up of approximately 3
years for chronic-phase CML (CP-CML) patients in the trial, Iclusig
continues to demonstrate anti-leukemic activity in patients with limited
treatment options. Deep and durable responses have been maintained in
CP-CML patients with 83 percent of CP-CML patients who achieved a
response, estimated to remain in major cytogenetic response (MCyR) at
three years. A copy of the press release is attached hereto as Exhibit
99.1 and is incorporated by reference into this Item 8.01of this Current
Report on Form 8-K.
On December 9, 2014, the Company issued a second press release
announcing long-term follow up data from the Phase 1 trial of Iclusig in
heavily pretreated patients with resistant or intolerant CML or Ph+ ALL.
The study now shows that with a median follow-up of four years in CP-CML
patients, Iclusig continues to demonstrate anti-leukemic activity in
patients with limited treatment options and that responses have been
maintained in CP-CML patients (n=43) with 72 percent having a MCyR, 65
percent having a complete cytogenetic response (CCyR) and 56 percent
having a major molecular response (MMR). A copy of the press release is
attached hereto as Exhibit 99.2 and is incorporated by reference into
this Item 8.01of this Current Report on Form 8-K.
Also on December 9, 2014, the Company issued a press release announcing
safety and efficacy follow-up data on Iclusig in patients with a
baseline T315I mutation from its Phase 1 and Phase 2 PACE trials in
heavily pretreated patients with resistant or intolerant CML or Ph+ ALL.
With a median follow-up of three years for CP-CML patients and nine
months overall, Iclusig continues to exhibit responses in patients with
the T315I mutation, for whom there is no other approved tyrosine kinase
inhibitor (TKI) therapy. Among patients with the T315I mutation, MCyR
was achieved by 92 percent (11/12) of CP-CML patients in the Phase 1
trial and 72 percent (46/64) of CP-CML patients in the PACE trial; taken
together, the combined MCyR rate for all T315I CP-CML patients was 75
percent. Long term safety data show that careful benefit-risk
evaluations should guide decisions to use and maintain ponatinib
therapy, particularly in patients who may be at increased risk for
arterial thrombotic events. A copy of the press release is attached
hereto as Exhibit 99.3 and is incorporated by reference into this Item
8.01of this Current Report on Form 8-K.
ITEM 9.01 Financial Statements and Exhibits.
(d) The following exhibits are filed with this report:
Exhibit
Number
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Description
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99.1
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Press Release dated December 8, 2014.
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99.2
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Press Release dated December 9, 2014.
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99.3
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Press Release dated December 9, 2014.
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THE PRESS RELEASES CONTAIN HYPERTEXT LINKS TO INFORMATION ON OUR
WEBSITE AND/OR OTHER WEBSITES. THE INFORMATION ON OUR WEBSITE AND ANY
OTHER WEBSITE IS NOT INCORPORATED BY REFERENCE INTO THIS CURRENT REPORT
ON FORM 8-K AND DOES NOT CONSTITUTE A PART OF THIS FORM 8-K.
SIGNATURES
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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December 11, 2014
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3
Exhibit 99.1
ARIAD
Announces Long-Term Safety and Efficacy Data of Ponatinib from Phase 2
Pace Clinical Trial
SAN FRANCISCO & CAMBRIDGE, Mass.--(BUSINESS WIRE)--December 8,
2014--ARIAD Pharmaceuticals, Inc. (NASDAQ:ARIA) today announced
long-term follow up from its pivotal Phase 2 trial of Iclusig®
(ponatinib), its approved BCR-ABL inhibitor, in heavily pretreated
patients with resistant or intolerant chronic myeloid leukemia (CML) or
Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL).
The study now shows that with a median follow-up of approximately 3
years for chronic-phase CML (CP-CML) patients in the trial, Iclusig
continues to demonstrate anti-leukemic activity in patients with limited
treatment options. Deep and durable responses have been maintained in
CP-CML patients with 83 percent of CP-CML patients who achieved a
response, estimated to remain in major cytogenetic response (MCyR) at
three years.
Additionally, the rate of maintenance of response in CP-CML patients was
high (greater than 90%) in patients who underwent Iclusig dose
reductions. Long-term safety data confirm that careful benefit-risk
evaluations should guide the decision to use and then maintain Iclusig
therapy, particularly in patients who may be at increased risk for
arterial thrombotic events.
The data were featured in a poster presentation on Sunday December 7, at
the 56th Annual Meeting of the American Society of Hematology
(ASH) taking place in San Francisco.
PACE Trial Update
The efficacy and safety of ponatinib in CML and Ph+ ALL patients
resistant or intolerant to dasatinib or nilotinib, or with the T315I
mutation, were evaluated in the pivotal Phase 2 PACE trial. A total of
449 patients were treated with ponatinib at a starting dose of 45 mg/day
Ninety-three percent of patients treated in the PACE trial had failed
two or more prior tyrosine kinase inhibitors (TKI), and 58 percent had
failed three or more prior TKIs.
Updated data in CP-CML patients (n=270) from the ongoing trial indicate
that with a median follow-up of 38.4 months (data as of October 6,
2014), 121 patients (45%) continue to receive ponatinib. Additional data
in CP-CML patients include:
-
55% of CP patients met the primary endpoint of MCyR by 12 months.
-
83% of patients who responded are estimated to remain in MCyR at 3
years.
-
39% of patients achieved a major molecular response (MMR) or better.
-
By Kaplan-Meier analysis, progression-free survival at 3 years is
estimated to be 61%.
-
Overall survival at 3 years is estimated to be 82%.
-
22% of CP patients experienced an arterial thrombotic serious adverse
event (SAE), and 27 percent of CP-CML patients experienced any
arterial thrombotic event, independent of severity or attribution of
relationship to ponatinib. There was no increase in the
exposure-adjusted incidence of newly occurring arterial thrombotic
events with longer follow-up.
-
4% of CP patients experienced a venous thrombotic SAE.
-
The most common all-grade treatment-emergent adverse events in CP-CML
were rash (46%), thrombocytopenia (45%), abdominal pain (45%),
headache (43%), constipation (41%) and dry skin (41%); the
discontinuation rate for adverse events was 17% in CP-CML.
“With a median follow-up of 3 years, there is no question that these are
very meaningful responses in a refractory CML patient population.
Responses such as this in a heavily pretreated patient population are
very encouraging,” stated Jorge E. Cortes, M.D., Professor and
Department Chair, Department of Leukemia, The University of Texas MD
Anderson Cancer Center. “Careful benefit-risk evaluation should guide
the decision to initiate ponatinib therapy, particularly in patients who
may be at increased risk for arterial thrombotic events. Ponatinib
continues to be a valuable treatment option for patients with refractory
CML and Ph+ ALL for whom the need and potential benefit outweigh the
risk.”
Efficacy Update Following Prospective Dose-Reduction Recommendations
(Data
from October 10, 2013 to October 6, 2014)
On October 10, 2013, following a partial clinical hold placed on new
patient enrollment in ARIAD-sponsored trials of ponatinib,
dose-reduction recommendations were provided by ARIAD to investigators
for patients remaining on the trial. The following dose reductions were
recommended, unless the benefit-risk analysis warranted treatment with a
higher dose:
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CP-CML patients who already achieved a MCyR should have their dose
reduced to 15 mg/day;
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CP-CML patients who had not already achieved MCyR should have their
dose reduced to 30 mg/day; and,
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Advanced-phase patients should have their dose reduced to 30 mg/day.
Now, with approximately one year of follow-up after these
recommendations, the rate of maintenance of response overall in CP-CML
is high -- whether or not patients underwent prospective dose reductions.
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Of the 64 patients who were in MCyR at the time of dose reductions, 61
patients (95%) maintained their response at 1 year following dose
reduction to either 30 mg or 15 mg.
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Of the 47 patients who were in MMR at the time of dose reductions, 44
patients (94%) maintained their response at 1 year following dose
reduction to either 30 mg or 15 mg.
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42 patients in MCyR did not undergo any dose reductions (the majority
of which were already at a reduced dose of 30 mg or 15 mg as of
October 10, 2013); of these, 39 patients (93%) maintained MCyR after 1
more year of ponatinib treatment.
Safety Update Following Prospective Dose-Reduction Recommendations
(Data from October 10, 2013 to October 6, 2014)
-
Of the patients who underwent prospective dose reduction, 5 of 70
patients (7%) without prior events had a new arterial thrombotic event
during the twelve-month interval following prospective dose reduction.
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Of the patients who did not undergo prospective dose reduction, 7 of
67 patients (10%) without prior events had a new arterial thrombotic
event in the same time interval.
“These data show that the majority of patients in the PACE trial
retained response, even when lowering the daily dose of Iclusig,” stated
Frank G. Haluska, M.D., Ph.D., senior vice president of clinical
research and development and chief medical officer at ARIAD. “The safety
and efficacy of Iclusig at starting doses lower than 45 mg will be
studied in a randomized trial set to begin next year.”
About Iclusig® (ponatinib) tablets
Iclusig is approved in the U.S., EU, Australia and Switzerland.
In the US, 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 updated clinical data 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.
Iclusig® is a registered trademark of ARIAD
Pharmaceuticals, Inc.
CONTACT:
ARIAD Pharmaceuticals, Inc.
For Investors
Kendra
Adams, 617-503-7028
Kendra.adams@ariad.com
or
For
Media
Liza Heapes, 617-620-4888
Liza.heapes@ariad.com
Exhibit 99.2
ARIAD
Announces Long-Term Safety and Efficacy Data of Ponatinib in
Chronic-Phase Chronic Myeloid Leukemia from Phase 1 Clinical Trial
~
Median Follow-up in Trial Now Four Years
CAMBRIDGE, Mass. & SAN FRANCISCO--(BUSINESS WIRE)--December 9,
2014--ARIAD Pharmaceuticals, Inc. (NASDAQ: ARIA) today announced
long-term follow up data from the Phase 1 trial of Iclusig®
(ponatinib), its approved BCR-ABL inhibitor, in heavily pretreated
patients with resistant or intolerant chronic myeloid leukemia (CML) or
Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL).
The study now shows that with a median follow-up of four years in
chronic phase CML (CP-CML) patients, Iclusig continues to demonstrate
anti-leukemic activity in patients with limited treatment options and
that responses have been maintained in CP-CML patients (n=43) with 72
percent having a major cytogenetic response (MCyR), 65 percent having a
complete cytogenetic response (CCyR) and 56 percent having a major
molecular response (MMR). Long-term safety data show that careful
benefit-risk evaluations should guide decisions to use and maintain
ponatinib therapy, particularly in patients who may be at increased risk
for arterial thrombotic events.
These data were featured in a poster presentation on December 8 at the 56th
Annual Meeting of the American Society of Hematology (ASH) taking place
in San Francisco.
“With nearly six years of treatment for some patients in this study,
ponatinib continues to demonstrate anti-leukemic responses in this
heavily pre-treated patient population,” stated Moshe Talpaz, M.D.,
Associate Director of Translational Research and Associate Chief of
Hematologic Malignancies, Trotman Professor of Leukemia Research, at the
University of Michigan Comprehensive Cancer Center. “We are continuing
to assess the safety profile of ponatinib and the impact of dose
reductions of ponatinib for patients with CML and Ph+ ALL for whom the
need and potential benefit outweigh the risk.”
Phase 1 Trial Long-Term Data
The Phase 1 dose-escalation study of ponatinib (starting dose range: 2
to 60 mg once daily) enrolled 81 patients with resistant or refractory
hematologic cancers, including 43 patients with chronic-phase CML. Sixty
percent of CP-CML patients in this study had failed at least three prior
tyrosine kinase inhibitors (TKI), and over 90 percent received at least
two prior TKIs. Twenty-two CP-CML patients (51 percent) remain on study.
Data presented at ASH focus on these CP-CML patients and represent
follow-up through September 26, 2014.
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Median follow-up for CP patients is now four years (49.9 months) with
the maximum follow-up now six years (69.9 months).
-
Of 22 ongoing CP patients, 14 are receiving 15 mg/day ponatinib, 5 are
at 30 mg/day, and 3 are at 45 mg/day. The mean current dose is 22.5
mg/day, and, the median dose intensity in these patients during the
course of the study is 34.2 mg/day.
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Anti-leukemic activity continues to be observed with ponatinib
treatment:
-
72 percent of CP patients had a MCyR, 65 percent had a complete
cytogenetic response (CCyR) and 56 percent had a MMR. Of note,
17/22 ongoing CP-CML patients (77 percent) are in deep molecular
response of MMR or better;
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The median time to MCyR, CCyR and MMR was 2.8, 5.5 and 7.4 months,
respectively;
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Median duration of MCyR, CCyR or MMR have not yet been reached.
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By Kaplan-Meier analysis, the probability of CP-CML patients
maintaining MCyR at 4 years was estimated as 68 percent.
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Ten of the 15 CP patients (67%) who started ponatinib at a dose of 30
mg or less achieved MCyR, comparable to the overall response rate of
72 percent.
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The most common treatment-emergent adverse events occurring in CP
patients were rash (65%), fatigue (60%), abdominal pain (58%),
headache (58%), and arthralgia (53%). When analyzed by year, most
adverse events occurred in the first year of treatment.
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Thirty percent (n=13) of CP patients experienced arterial thrombotic
serious adverse events (SAEs), and 40 percent of CP-CML patients
experienced any arterial thrombotic event, independent of severity.
There were two venous thrombotic events and no serious venous
thrombotic events.
“The long-term follow-up of results of the Phase 1 study of ponatinib in
patients with chronic myeloid leukemia in the chronic phase shows that
responding patients can achieve lasting, deep responses,” said Frank G.
Haluska, M.D., Ph.D., chief medical officer and senior vice president,
clinical R&D at ARIAD Pharmaceuticals. “These results inform the
strategy of the planned randomized study of ponatinib doses, and the
observed robust response rates and response durations support testing
lower doses in refractory patients. The dose ranging study is planned to
begin in 2015.”
About Iclusig® (ponatinib) tablets
Iclusig is approved in the U.S., EU, Switzerland and Australia.
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 updated clinical data 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.
Iclusig® is a registered trademark of ARIAD
Pharmaceuticals, Inc.
CONTACT:
ARIAD Pharmaceuticals, Inc.
For Investors
Kendra
Adams, 617-503-7028
Kendra.adams@ariad.com
or
For
Media
Liza Heapes, 617-620-4888
Liza.heapes@ariad.com
Exhibit 99.3
ARIAD
Announces Follow-up Data from Phase 1 and PACE Trials of Ponatinib in
Patients with T315I Mutation in Chronic Myeloid Leukemia
CAMBRIDGE, Mass. & SAN FRANCISCO--(BUSINESS WIRE)--December 9,
2014--ARIAD Pharmaceuticals, Inc. (NASDAQ: ARIA) today announced safety
and efficacy follow-up data on Iclusig® (ponatinib), its
approved BCR-ABL inhibitor, in patients with a baseline T315I mutation
from its Phase 1 and Phase 2 PACE trials in heavily pretreated patients
with resistant or intolerant chronic myeloid leukemia (CML) or
Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL).
With a median follow-up of three years for CP-CML patients and nine
months overall, Iclusig continues to exhibit responses in patients with
the T315I mutation, for whom there is no other approved tyrosine kinase
inhibitor (TKI) therapy. Among patients with the T315I mutation, major
cytogenetic response (MCyR) was achieved by 92 percent (11/12) of
chronic phase CML patients (CP-CML) in the Phase 1 trial and 72 percent
(46/64) of CP-CML patients in the PACE trial; taken together, the
combined MCyR rate for all T315I CP-CML patients was 75 percent.
Long-term safety data show that careful benefit-risk evaluations should
guide decisions to use and maintain ponatinib therapy, particularly in
patients who may be at increased risk for arterial thrombotic events.
These data were featured on Monday December 8, at the 56th
Annual Meeting of the American Society of Hematology (ASH) taking place
in San Francisco.
“For CML patients with the T315I mutation, there were few treatment
options available prior to ponatinib, and prognosis for these patients
was poor. Now, with nearly six years of treatment for some patients in
these trials, we have longer term data demonstrating that ponatinib
continues to evoke responses in these CP-CML patients,” stated Michael
J. Mauro, M.D., Leader, Myeloproliferative Neoplasms Programs, at the
Memorial Sloan Kettering Cancer Center. “With these follow-up data,
overall survival of 78 percent is now estimated at three years for
chronic-phase patients with the T315I mutation in these trials.”
Phase 1 and PACE Data in Patients with T315I
The analysis describes the pooled efficacy and safety of ponatinib in
patients with a T315I mutation detected at baseline from the ongoing
Phase 1 dose-escalation study and Phase 2 PACE trials. The analysis
includes 147 patients with a T315I mutation from the Phase 1 (n=19) and
PACE (n=128) trials. Half of the 76 CP-CML patients with T315I remain on
treatment and 44 (30%) total patients (all disease phases) with T315I
remain on treatment in the respective trials. Data presented on these
patients are as of September 26, 2014 for the Phase 1 trial and October
6, 2014 for the PACE trial.
-
Median follow-up for all T315I patients in this analysis is 8.9
months. The median follow-up for CP-CML patients with T315I (n=76) is
three years (maximum follow-up, 70 months).
-
In these heavily pre-treated T315I patients, 45 percent of the total
patients had received treatment with two prior TKIs, and 40 percent
had received three or more prior TKIs. In patients with CP-CML, 46
percent had received two prior TKIs, and 39 percent had three or more
prior TKIs.
-
For CP patients, responses continue to be observed in T315I patients
treated with ponatinib at 3 years. In the combined analysis of these
patients from both trials:
-
75 percent of all CP-CML patients achieved MCyR, 72 percent
achieved a complete cytogenetic response (CCyR), and 61 percent
achieved a major molecular response (MMR).
-
By Kaplan-Meier estimate, 83 percent of these CP patients were
estimated to maintain MCyR at 3 years, and 81 percent were
estimated to maintain CCyR at 3 years. The median duration of
response has not yet been reached.
-
58 percent of advanced phase (AP) CML patients with T315I achieved
major hematologic response (MaHR), the end-point for those
patients in the trials. Twenty-seven percent of blast phase (BP)
CML patients, and 38 percent of Ph+ ALL patients achieved MaHR.
-
The probability for overall survival in CP patients with T315I at 36
months is 78 percent and 63 percent for patients with AP-CML.
-
The most common treatment-emergent adverse events in T315I patients
(all disease phases) were rash (42%), abdominal pain (39%), headache
(39%), and nausea (36%). The most common serious treatment-emergent
adverse events were neoplasm progression (10%), pneumonia (7%), and
acute myocardial infarction (5%).
-
Thirty-two percent (n=24) of CP-CML patients with T315I experienced
arterial thrombotic events, and 7 percent experienced a venous
thrombotic event (VTE). Exposure-adjusted incidences of arterial and
venous thrombotic events in patients with the T315I mutation were
similar to those observed in the overall patient population.
“Ponatinib is the only TKI approved for patients with the T315I mutation
of BCR-ABL, which is a common mutation that is associated with
resistance in Philadelphia-positive leukemias,” said Frank G. Haluska,
M.D., Ph.D., chief medical officer and senior vice president, clinical
R&D at ARIAD Pharmaceuticals. “The combined data from the two ongoing
trials of ponatinib show continued, clinically meaningful responses in
this difficult-to-treat patient population.”
About Iclusig® (ponatinib) tablets
Iclusig is approved in the U.S., EU, Switzerland and Australia.
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 updated clinical data 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.
Iclusig® is a registered trademark of ARIAD
Pharmaceuticals, Inc.
CONTACT:
ARIAD Pharmaceuticals, Inc.
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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