Investor Briefing and Webcast Today, June 2,
at 7:30 a.m. CT
ARIAD Pharmaceuticals, Inc. (NASDAQ:ARIA) today announced
longer-term follow up from its Phase 1 and pivotal Phase 2 trials
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 studies now show that with a
median follow-up of 42.5 months for chronic-phase CML (CP-CML)
patients in the Phase 1 trial, Iclusig continues to demonstrate
anti-leukemic activity in those who had limited treatment options,
and that deep and durable responses have been maintained in CP-CML
patients in the PACE trial with 87 percent estimated to remain in
major cytogenetic response (MCyR) at two years. Longer-term safety
data show that careful benefit/risk evaluation should guide the
decision to use ponatinib therapy, particularly in patients who may
be at increased risk for vascular occlusive events.
These data are being featured this afternoon in two poster
presentations at the 2014 American Society of Clinical Oncology
(ASCO) annual meeting taking place in Chicago, Illinois.
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.
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 prior TKIs. A total of 449 patients were
treated with ponatinib in the PACE trial. The starting dose in the
PACE trial was 45 mg/day.
Updated efficacy and safety data in CP-CML patients (n=270) from
the ongoing PACE trial presented at ASCO include that with a median
follow-up of 30 months (data as of January 6, 2014), 136 CP-CML
patients (50 percent) continue to receive ponatinib in the trial.
Additional data in CP-CML include:
- A median time to response (MCyR) of 2.8
months.
- 87 percent of patients estimated to
remain in MCyR at 2 years.
- 38 percent of patients achieved a major
molecular response (MMR) or better.
- Progression free survival at 2 years is
estimated to be 67 percent.
- Overall survival at 2 years is
estimated to be 86 percent.
- 18 percent of CP-CML patients
experienced a vascular occlusive serious adverse event (SAE), and
25 percent of CP-CML patients experienced any vascular occlusive
event, independent of severity or attribution.
- 16 percent of CP-CML patients
experienced an arterial occlusive SAE.
- The most common all-grade
treatment-emergent adverse events were thrombocytopenia (45%), rash
(45%) and abdominal pain (44%); discontinuation rate for adverse
events was 17 percent in CP-CML.
“Ponatinib continues to demonstrate substantial clinical
activity in these heavily pretreated patients, with responses
regardless of mutation status or disease state,” stated Hagop M.
Kantarjian, M.D., Professor and Chair, Department of Leukemia, The
University of Texas MD Anderson Cancer Center. “Deep and durable
response rates have been maintained with longer follow-up in the
PACE trial.”
On October 10, 2013, a partial clinical hold was placed on new
patient enrollment in ARIAD-sponsored trials of ponatinib due to an
accumulation of arterial thrombotic events observed after longer
follow-up. The following dose reduction recommendations were
provided by ARIAD to investigators for patients remaining on the
PACE and Phase 1 trials, unless the benefit/risk analysis warranted
treatment with a higher dose:
- CP-CML patients who already achieved a
MCyR should have their dose reduced to 15 mg/day,
- CP-CML patients who had not already
achieved MCyR should have their dose reduced to 30 mg/day, and
- Advanced-phase patients should have
their dose reduced to 30mg/day
PACE Trial Efficacy Update Following Dose Modification
Recommendations
(Data from October 10, 2013 to April 7, 2014)
- Of 126 CP-CML patients who had a
follow-up visit during this six-month interval after dose
modification recommendations were issued, almost all patients on
trial maintained their response. Dose reductions were not typically
associated with a loss of response; further follow up and
evaluation of these patients continues.
- Overall, the rate of maintenance of
response was consistent with that reported before dose-reduction
recommendations were provided.
- 23 patients had a cytogenetic
assessment. Of these, no patient lost response due to dose
reduction following partial clinical hold. One patient lost MCyR
since October 10, 2013; this patient already had the dose reduced
prior to issuance of dose modification recommendations.
- 126 patients had a molecular
assessment. Of these, 4 patients lost MMR) since October 10, 2013,
only one of whom had the dose reduced during this timeframe.
PACE Trial Safety Update Following Dose Modification
Recommendations
- New vascular occlusive serious adverse
events (SAE) during the six-month interval following dose
modification occurred predominantly in patients who did not undergo
dose reduction; further follow up and evaluation of these patients
continues.
- Overall, 3 patients had a first
vascular occlusive SAE during this interval (2 while maintaining
dose; 1 after dose reduction).
- Overall, 8 patients who had a prior
vascular occlusive event had another during this interval. Two of
these patients who had a non-serious vascular occlusive event
previously on study had a vascular occlusive SAE during the
interval (1 while maintaining dose and 1 after reducing dose). Six
patients who had a vascular occlusive SAE previously on study had
another vascular occlusive SAE during the interval (4 while
maintaining dose and 2 after reducing dose).
“These data show retention of response and maintenance of
response, even when lowering the daily dose of ponatinib,” added
Dr. Kantarjian. “Careful benefit/risk evaluation should guide the
decision to initiate ponatinib therapy, particularly in patients
who may be at increased risk for vascular occlusive event.
Ponatinib continues to be an important treatment option for
patients with CML and Ph-positive ALL for whom the need and
potential benefit outweigh the risk.”
Phase 1 Trial Longer-Term Data
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). Twenty-four CP-CML patients
remain on study. Data presented at ASCO focus on these CP-CML
patients and are as of January 6, 2014.
- Median follow-up for CP-CML patients is
now 42.5 months (maximum follow-up is 59.1 months).
- The mean current dose in continuing
CP-CML patients is 24 mg/day, and the mean dose intensity in these
patients during the course of the study is 34 mg/day.
- Durable anti-leukemic activity
continues to be observed with ponatinib treatment:
- 72 percent of CP-CML patients had a
MCyR, 65 percent had a complete cytogenetic response (CCyR) and 51
percent of patients had MMR.
- Median durations of MCyR, CCyR and MMR
are not yet reached.
- Of 12 CP-CML patients with the T315I
mutation, 1 discontinued; 10 of the 11 ongoing patients achieved
MCyR.
- Adverse events (AE) were generally
manageable by dose reduction or interruption. The most common AE
occurring after one year of therapy was fatigue. Abdominal pain
(12%) and increased lipase (9%) were the most common grade 3
AEs.
- Twenty-eight percent (n=12) of CP-CML
patients experienced vascular occlusive SAEs, representing an
accumulation of events with continued long-term follow-up.
“These data show notable response duration of nearly five years
of ponatinib therapy and a median duration of response yet to be
reached,” stated Moshe Talpaz, M.D., Associate Director of
Translational Research and Associate Chief of Hematologic
Malignancies, Trotman Professor of Leukemia Research, University of
Michigan Medical Center. “We continue to learn about the adverse
event profile of ponatinib, including vascular events, while
recognizing that ponatinib continues to demonstrate anti-leukemic
activity in patients who have limited treatment options.”
Investor and Analyst Briefing and Webcast
ARIAD will host an investor and analyst briefing from ASCO on
Monday June 2, 2014. This breakfast meeting will feature Dr.
Lyudmila Bazhenova from UC San Diego Moores Cancer Center to
discuss the AP26113 clinical data being presented at ASCO, Dr.
Michael J. Mauro from Memorial Sloan Kettering Cancer Center to
discuss clinical data on ponatinib in CML, and Dr. Michael C.
Heinrich from Oregon Health and Science University to discuss
ponatinib clinical data in GIST.
The meeting will be webcast live along with slides and can be
accessed by visiting the investor relations section of the
Company’s website at http://investor.ariad.com.
Date: Monday, June 2, 2014 Time:
7:30 a.m. to 8:30 a.m. (CT) Location: Hilton Chicago, Marquette
Room
A replay of the investor event will be available on the ARIAD
website approximately three hours after the presentation and will
be archived on the site for four weeks. To ensure a timely
connection to the live webcast, participants should log onto the
webcast at least 15 minutes prior to the scheduled start time.
About Iclusig® (ponatinib) tablets
Iclusig is approved in the U.S., EU and Switzerland. Iclusig is
a kinase inhibitor indicated in the U.S. 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.
ARIAD Pharmaceuticals, Inc.For Investors:Kendra Adams,
617-503-7028Kendra.adams@ariad.comorFor MediaLiza Heapes,
617-620-4888Liza.heapes@ariad.com
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