ARIAD Pharmaceuticals, Inc. (NASDAQ: ARIA) and Medison Pharma
Ltd, Israel's leading international marketing group for
innovative pharmaceuticals, today announced that the Israeli
Ministry of Health has granted regulatory approval for Iclusig®
(ponatinib) in Israel for adult patients with:
- Chronic phase, accelerated phase, or
blast phase chronic myeloid leukaemia (CML) who are resistant to
dasatinib or nilotinib, who are intolerant to dasatinib or
nilotinib and for whom subsequent treatment with imatinib is not
clinically appropriate, or who have the T315I mutation
- Philadelphia chromosome-positive acute
lymphoblastic leukaemia (Ph+ ALL) who are resistant to dasatinib,
who are intolerant to dasatinib and for whom subsequent treatment
with imatinib is not clinically appropriate, or who have the T315I
mutation.
ARIAD submitted its application for Iclusig to the Israeli
Ministry of Health in June 2014. Commercial launch of Iclusig is
expected to occur in the second quarter of 2015.
“Iclusig is an important addition to the treatment
armamentarium,” said Professor Arnon Nagler, head of hematology and
the Bone Marrow Transplant Division at the Chaim Sheba Medical
Center in Israel, and chairman of the Israeli Bone Marrow
Transplant Association. Dr. Nagler added, “Patients in Israel have
an excellent health care system, and having this potent and
promising drug is an important addition to the national health
basket.”
“The swift approval by the Ministry of Health in Israel speaks
to the importance of this new therapy to appropriate patients in
Israel. We look forward to continued success working with ARIAD and
fulfilling Medison’s vision to provide innovative and unique
treatments to patients in Israel,” said Meir Jakobsohn, chief
executive officer and founder of Medison Pharma.
“We are very pleased with the rapid approval of Iclusig in
Israel and the strength of our ongoing collaboration with Medison.
This milestone further recognizes the major importance of Iclusig
for the treatment of patients with refractory Philadelphia-positive
leukemias,” stated Harvey J. Berger, M.D., chairman and chief
executive officer of ARIAD. “Approval in Israel is an important
step in our effort to make Iclusig available to CML patients in
need in key regions throughout the world.”
The Ministry of Health decision was based on results from the
pivotal Phase 2 PACE (Ponatinib Ph+ ALL and CML Evaluation) trial
in patients with CML or Ph+ ALL who were resistant or intolerant to
prior tyrosine kinase inhibitor (TKI) therapy, or who had the T315I
mutation of BCR-ABL. Iclusig demonstrated anti-leukemic activity
achieving a major cytogenetic response (MCyR) in 54 percent of
chronic-phase CML patients and in 70 percent of patients with the
T315I mutation.1, 2 MCyR within the first 12 months was the primary
endpoint of the PACE trial for chronic-phase patients.1, 2
In patients with advanced disease, 57 percent of
accelerated-phase CML patients and 34 percent of blast-phase CML
patients achieved a major hematologic response (MaHR) with Iclusig.
MaHR within the first 6 months was the primary endpoint in the
trial for patients with advanced disease. 1, 2
The most common serious adverse reactions >1% were
pancreatitis, pyrexia, abdominal pain, myocardial infarction,
atrial fibrillation, anaemia, platelet count decreased, febrile
neutropenia, cardiac failure, lipase increased, dyspnea, diarrhoea,
neutrophil count decreased, pancytopenia, and pericardial
effusion.
Serious arterial cardiovascular, cerebrovascular, and peripheral
vascular occlusive adverse reactions occurred in 6.7%, 5.6%, and
5.1% of Iclusig treated patients, respectively. Serious venous
occlusive reactions occurred in 4.5% of patients. The most common
(≥20%) adverse reactions of any severity were decrease in platelet
count, rash, dry skin, and abdominal pain.2
Based on the European Medicines Agency’s orphan drug designation
and the HAEMACARE project, it is estimated that there are
approximately 700 patients with CML in Israel.
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,
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 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 Medison
Medison is Israel’s leading marketing group, representing
innovative niche healthcare products from companies such as Biogen
Idec, Amgen, Shire and Ipsen. Medison has built and maintained
long-standing relations with HMOs, local medical centers and
physicians. Backed by three generations of experience in the
healthcare industry since 1937, Medison is uniquely qualified to
provide the complete spectrum of integrated services for
international companies looking to enter or expand their presence
in the Israeli. Medison has an office and is very also active in
Romania. For more information, visit www.medisonpharma.com.
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).
Iclusig® is a registered trademark of ARIAD
Pharmaceuticals, Inc.
Reference:1. Cortes JE, et al. N Engl J Med. 2013;
369:1783-96.2. ICLUSIG (ponatinib) European Summary of Product
Characteristics
ARIAD Forward-Looking Statement
This press release contains forward-looking statements. Any
statements contained herein which do not describe historical facts,
including but not limited to, statements regarding: the expected
timing for commercial launch of Iclusig in Israel; the therapeutic
and commercial potential of Iclusig; the strength of our
collaboration with Medison; and our efforts to make Iclusig
available in additional markets, are forward-looking statements
which are based on our management's good-faith 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 factors, risks and uncertainties include, among others: our
ability to manufacture, and supply Iclusig to Medison; the ability
of Medison to perform the contracted services, such as obtaining
pricing and reimbursement approval for Iclusig in Israel; Medison’s
ability to distribute, promote, market and sell Iclusig in Israel;
the level of pricing and reimbursement obtained in Israel; the
timing and success of sales of Iclusig in Israel; the costs
associated with our development and manufacturing, commercial and
other activities; the adequacy of capital resources and the
availability of additional funding; and those additional factors
detailed in our public filings with the U.S. Securities and
Exchange Commission, including our most recent Annual Report on
Form 10-K and subsequent Quarterly Reports on Form 10-Q. Except as
otherwise noted, these forward-looking statements speak only as of
the date of this press release and we undertake no obligation to
update or revise any of these statements to reflect events or
circumstances occurring after this press release. We caution
investors not to place considerable reliance on the forward-looking
statements contained in this press release. All forward‐looking
statements in this press release are qualified in their entirety by
this cautionary statement.
For ARIAD InvestorsKendra Adams,
617-503-7028Kendra.adams@ariad.comorFor ARIAD MediaLiza
Heapes, 617-621-2315Liza.heapes@ariad.comorFor
MedisonGoldfinger CommunicationsLidor Jacob,
972-3-5620024lidor@goldfingercom.com
Ariad (NASDAQ:ARIA)
Historical Stock Chart
From Mar 2024 to Apr 2024
Ariad (NASDAQ:ARIA)
Historical Stock Chart
From Apr 2023 to Apr 2024