Investor conference call today, December 20, at
11:30 a.m. E.T.
ARIAD Pharmaceuticals, Inc. (NASDAQ: ARIA) today announced that
the U.S. Food and Drug Administration (FDA) has approved revised
U.S. Prescribing Information (USPI) and a Risk Evaluation and
Mitigation Strategy (REMS) for Iclusig® (ponatinib) that allows
immediate resumption of its marketing and commercial distribution.
The USPI includes a revised indication statement and boxed warning,
updated safety information and recommendations regarding dosing
considerations for prescribers.
ARIAD Pharmaceuticals, Inc., based in
Cambridge, MA (Photo: Business Wire)
Iclusig is now 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 (Ph+) acute
lymphoblastic leukemia, and
- Chronic phase, accelerated phase, or
blast phase chronic myeloid leukemia or Ph+ acute lymphoblastic
leukemia for whom no other tyrosine-kinase inhibitor therapy is
indicated.
The FDA granted approval of the revised USPI based on its review
of the Iclusig clinical-trial data, including 24-month follow up of
the pivotal PACE trial. The boxed warning has been revised to alert
patients and healthcare professionals to the risk of vascular
occlusive events and includes a new warning for heart failure. The
starting dose of Iclusig remains 45 mg daily.
“In less than two months of suspending marketing and commercial
distribution of Iclusig in the U.S., we addressed the issues raised
by the FDA and now are able to market and distribute Iclusig again
in the U.S.,” stated Harvey J. Berger, M.D. chairman and chief
executive officer of ARIAD. “As we look ahead to re-launching
Iclusig in the U.S. and fulfilling our post-marketing requirements,
we will continue to focus on understanding the benefits and risks
of Iclusig treatment in patients with resistant or intolerant
Philadelphia-positive leukemias.”
At the end of October 2013, there were approximately 640
patients receiving Iclusig obtained through commercial channels in
the U.S. Since then, Iclusig has been made available through
emergency and single-patient investigational new drug (IND)
applications, which were reviewed and approved by the FDA on a
case-by-case basis. Through today, FDA has approved 350 INDs. This
figure includes approximately 260 patients who have already
received Iclusig and approximately 90 additional patients who have
been approved to receive Iclusig through these mechanisms.
“We are committed to continuing our productive collaboration
with the FDA and to helping patients and their physicians make
informed decisions about the most appropriate use of Iclusig in the
context of the revised product label,” stated Frank Haluska, M.D.,
Ph.D., senior vice president and chief medical officer of
ARIAD.
“Commercial distribution of Iclusig will begin by mid-January at
which time we will deploy dedicated commercial and medical affairs
teams in the U.S. In the meantime, patients will continue to
receive Iclusig through the IND mechanism,” stated Marty Duvall,
executive vice president and chief commercial officer. “We expect
the commercialization of Iclusig to be cash-flow positive from the
onset.”
REMS Program and Post-Marketing Requirements
The objective of the REMS program is to inform prescribers of
the risk of vascular occlusion associated with Iclusig and of the
revised indications. The REMS program, which will be initiated
within three weeks, includes letters to physicians and professional
societies, a fact sheet and information that will be communicated
through professional journals and displayed at scientific meetings.
All of these materials will be available on an Iclusig REMS
website.
In addition, ARIAD has agreed to fulfill a series of
post-marketing requirements beginning in 2014 to better understand
the risks of vascular occlusion and to further explore various
doses of Iclusig, as follows:
- Enhanced pharmacovigilance assessment
of risk factors for, and the management and consequences of,
vascular occlusive events that are serious or require medical
evaluation or treatment, occurring while patients are receiving
Iclusig administered in clinical trials or obtained through
commercial channels,
- Prospective observation of patients on
Iclusig obtained through commercial channels to evaluate the
incidence of, and risk factors for, vascular occlusive events when
Iclusig is given with or without anticoagulant or antiplatelet
agents,
- Continued follow-up of patients from
the three ARIAD-sponsored trials of Iclusig in
Philadelphia-positive leukemias to assess the long-term safety of
Iclusig treatment, including the long-term risk of vascular
occlusive events, and
- A randomized, multi-arm trial to
characterize a range of Iclusig doses and to inform its safe use in
patients with refractory, chronic-phase chronic myeloid
leukemia.
Today’s Conference Call at 11:30 a.m. ET
ARIAD management will host a conference call and webcast to
discuss the approval of a new U.S. product label for Iclusig today,
December 20 at 11:30 a.m. ET. The live webcast can be accessed by
visiting the investor relations section of the Company’s website at
http://investor.ariad.com. The call can be accessed by dialing
888-771-4371 (U.S.) or +1 847-585-4405 (international) and
providing the participant code 36331249. A replay of the call will
be available on the ARIAD website approximately two hours after
completion of the call and will be archived for three weeks.
About Iclusig® (ponatinib)
Iclusig is a kinase inhibitor. The primary target for Iclusig is
BCR-ABL, an abnormal tyrosine kinase that is expressed in chronic
myeloid leukemia (CML) and Philadelphia-chromosome positive acute
lymphoblastic leukemia (Ph+ ALL). Iclusig was designed using
ARIAD’s computational and structure-based drug design platform
specifically to inhibit the activity of BCR-ABL. Iclusig targets
not only native BCR-ABL but also its isoforms that carry mutations
that confer resistance to treatment, including the T315I mutation,
a common mutation which has been associated with resistance to
other approved TKIs.
IMPORTANT SAFETY INFORMATION, INCLUDING THE BOXED
WARNING
WARNING: VASCULAR OCCLUSION, HEART FAILURE, and
HEPATOTOXICITY
See full U.S. 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 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, the timing and financial success of
the resumption of commercial marketing and sales of Iclusig; the
Company's ability to fulfill the four post-marketing requirements
to the satisfaction of the FDA; the timing and results of the
enhanced pharmacovigilance study, the prospective observational
study and the long-term follow-up of subjects in Iclusig clinical
studies; the timing, enrollment and results of the randomized,
multi-arm trial to characterize a range of Iclusig doses; and the
safety profile for Iclusig as it continues to be studied.
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.
Photos/Multimedia Gallery Available:
http://www.businesswire.com/multimedia/home/20131220005569/en/
ARIAD Pharmaceuticals, Inc.For InvestorsKendra Adams,
617-503-7028Kendra.adams@ariad.comorMaria Cantor,
617-621-2208Maria.cantor@ariad.comorFor MediaBill Berry,
212-253-8881bberry@berrypr.comorAndrea Coan,
212-253-8881acoan@berrypr.com
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