JERUSALEM--(BUSINESS WIRE)--Jan. 15, 2018--
Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA) announced that
the U.S. Food and Drug Administration (FDA) has approved the use of
TRISENOX® (arsenic trioxide) injection in combination
with tretinoin for the treatment of adults with newly-diagnosed low-risk
acute promyelocytic leukemia (APL) whose APL is characterized by the
presence of the t(15;17) translocation or PML/RAR-alpha gene expression.
The approval was based on a Priority Review by the FDA on data from
published scientific literature and a review of Teva’s global safety
database for arsenic trioxide.
“Today’s approval to expand the indication of TRISENOX is a testament to
Teva’s commitment to providing solutions to advance cancer care,” said
Paul Rittman, Senior Vice President and General Manager, Teva Oncology.
“This label expansion represents an important benefit as TRISENOX is now
an FDA-approved first line treatment option for patients with acute
promyelocytic leukemia.”
The new indication reinforces the current practice guidelines by the
National Comprehensive Cancer Network® (NCCN).
Please see the Full
Prescribing Information for TRISENOX® and the Important
Safety Information below including Boxed Warning regarding: DIFFERENTIATION
SYNDROME AND CARDIAC CONDUCTION ABNORMALITIES.
TRISENOX® (arsenic trioxide) Injection
IMPORTANT SAFETY INFORMATION
WARNING: DIFFERENTIATION SYNDROME AND CARDIAC CONDUCTION ABNORMALITIES
Differentiation Syndrome: Patients with acute promyelocytic leukemia
(APL) treated with TRISENOX have experienced symptoms of differentiation
syndrome, which can be fatal if not treated. Symptoms may include fever,
dyspnea, acute respiratory distress, pulmonary infiltrates, pleural or
pericardial effusions, weight gain or peripheral edema, hypotension, and
renal, hepatic, or multi-organ dysfunction, in the presence or absence
of leukocytosis. If differentiation syndrome is suspected, immediately
initiate high-dose corticosteroid therapy and hemodynamic monitoring
until resolution of signs and symptoms. Temporary discontinuation of
TRISENOX may be required.
Cardiac Conduction Abnormalities: Arsenic trioxide can cause QTc
interval prolongation, complete atrioventricular block, and a torsade de
pointes-type ventricular arrhythmia, which can be fatal. Before
initiating therapy, assess the QTc interval, correct pre-existing
electrolyte abnormalities, and consider discontinuing drugs known to
prolong QTc interval. Do not administer TRISENOX to patients with
ventricular arrhythmia or prolonged QTcF.
Contraindications: TRISENOX is contraindicated in patients who
are hypersensitive to arsenic.
Differentiation Syndrome: In clinical trials, 16-23% of patients
treated with TRISENOX for APL developed differentiation syndrome.
Differentiation syndrome has been observed with and without concomitant
hyperleukocytosis, and it has occurred as early as day 1 of induction to
as late as the second month induction therapy. When TRISENOX is used in
combination with tretinoin, prednisone prophylaxis is advised.
Cardiac Conduction Abnormalities: In the clinical trials of
patients with newly-diagnosed low-risk APL treated with TRISENOX in
combination with tretinoin, 11% experienced QTc prolongation > 450 msec
for men and > 460 msec for women throughout the treatment cycles. In the
clinical trial of patients with relapsed or refractory APL treated with
TRISENOX monotherapy, 40% had at least one ECG tracing with a QTc
interval greater than 500 msec. A prolonged QTc was observed between 1
and 5 weeks after start of TRISENOX infusion, and it usually resolved by
8 weeks after TRISENOX infusion. There are no data on the effect of
TRISENOX on the QTc interval during the infusion of the drug.
The risk of torsade de pointes is related to the extent of QT
prolongation, concomitant administration of QT prolonging drugs, a
history of torsade de pointes, pre-existing QT interval prolongation,
congestive heart failure, administration of potassium-wasting diuretics,
or other conditions that result in hypokalemia or hypomagnesemia. The
risk may be increased when TRISENOX is co-administered with medications
that can lead to electrolyte abnormalities (such as diuretics or
amphotericin B).
Hepatotoxicity: In the clinical trials, 44% of patients with
newly-diagnosed low-risk APL treated with TRISENOX in combination with
tretinoin experienced elevated aspartate aminotransferase (AST),
alkaline phosphatase, and/or serum bilirubin. These abnormalities
resolved with temporary discontinuation of TRISENOX and/or tretinoin.
During treatment with TRISENOX, monitor liver chemistries at least 2-3
times per week through recovery from toxicities. Withhold treatment with
TRISENOX and/or tretinoin if elevations in AST), alkaline phosphatase,
and/or serum bilirubin occur to greater than 5 times the upper limit of
normal.
Long-term liver abnormalities can occur in APL patients treated with
TRISENOX in combination with tretinoin. In a published series, mild
liver dysfunction and hepatic steatosis were seen in 15% and 43%,
respectively, of patients at a median of 7 years (range 0-14 years)
after treatment with arsenic trioxide in combination with tretinoin.
Carcinogenesis: The active ingredient of TRISENOX, arsenic
trioxide, is a human carcinogen. Monitor patients for the development of
second primary malignancies.
Embryo-Fetal Toxicity: TRISENOX can cause fetal harm when
administered to a pregnant woman. One patient who became pregnant while
receiving arsenic trioxide had a miscarriage. Conduct pregnancy tests
prior to starting treatment and advise pregnant women of the potential
risk to a fetus. Advise patients of reproductive potential to use
effective contraception during treatment with TRISENOX and after
treatment for 6 months in females and 3 months in males. TRISENOX may
also impair fertility in males.
Lactation: TRISENOX is excreted in human milk. Because of the
potential for serious adverse reactions in the breastfed child,
discontinue breastfeeding during treatment with TRISENOX and for two
weeks after the final dose.
Patients with Renal Impairment: Exposure of arsenic trioxide may
be higher in patients with severe renal impairment. Patients with severe
renal impairment (creatinine clearance less than 30 mL/min) should be
monitored for toxicity when these patients are treated with TRISENOX,
and a dose reduction may be warranted. The use of TRISENOX in patients
on dialysis has not been studied.
Patients with Hepatic Impairment: Since limited data are
available across all hepatic impairment groups, caution is advised in
the use of TRISENOX in patients with hepatic impairment. Monitor
patients with severe hepatic impairment (Child-Pugh Class C) who are
treated with TRISENOX for toxicity.
Most Common Adverse Reactions: The most common adverse reactions
(greater than 30%) were leukocytosis, neutropenia, thrombocytopenia,
nausea, vomiting, diarrhea, abdominal pain, hepatic toxicity, fever,
rigors, fatigue, insomnia, tachycardia, QTc prolongation, edema,
hyperglycemia, hypokalemia, hypomagnesemia, dyspnea, cough, rash or
itching, sore throat, arthralgia, headaches, paresthesia, and dizziness.
TO REPORT SIDE EFFECTS: Contact us at 1-888-483-8279 or USMedinfo@tevapharma.com
Indications
TRISENOX® is indicated:
-
In combination with tretinoin for treatment of adults with
newly-diagnosed low-risk acute promyelocytic leukemia (APL) whose APL
is characterized by the presence of the t(15;17) translocation or
PML/RAR-alpha gene expression.
-
For induction of remission and consolidation in patients with APL who
are refractory to, or have relapsed from, retinoid and anthracycline
chemotherapy, and whose APL is characterized by the presence of the
t(15;17) translocation or PML/RAR-alpha gene expression.
About Teva
Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA) is a leading
global pharmaceutical company that delivers high-quality,
patient-centric healthcare solutions used by approximately 200 million
patients in 100 markets every day. Headquartered in Israel, Teva is the
world’s largest generic medicines producer, leveraging its portfolio of
more than 1,800 molecules to produce a wide range of generic products in
nearly every therapeutic area. In specialty medicines, Teva has the
world-leading innovative treatment for multiple sclerosis as well as
late-stage development programs for other disorders of the central
nervous system, including movement disorders, migraine, pain and
neurodegenerative conditions, as well as a broad portfolio of
respiratory products. Teva is leveraging its generics and specialty
capabilities in order to seek new ways of addressing unmet patient needs
by combining drug development with devices, services and technologies.
Teva's net revenues in 2016 were $21.9 billion. For more information,
visit www.tevapharm.com.
Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements within the
meaning of the Private Securities Litigation Reform Act of 1995
regarding the expanded indication for TRISENOX®, which are based on
management’s current beliefs and expectations and are subject to
substantial risks and uncertainties, both known and unknown, that could
cause our future results, performance or achievements to differ
significantly from that expressed or implied by such forward-looking
statements. Important factors that could cause or contribute to such
differences include risks relating to:
-
the uncertainty of commercial success of TRISENOX®;
-
our specialty medicines business, including: competition for our
specialty products, especially Copaxone®, our
leading medicine, which faces competition from existing and potential
additional generic versions and orally-administered alternatives; our
ability to achieve expected results from investments in our product
pipeline; competition from companies with greater resources and
capabilities; and the effectiveness of our patents and other measures
to protect our intellectual property rights;
-
our business and operations in general, including: uncertainties
relating to the potential success and our ability to effectively
execute a restructuring plan; uncertainties relating to the potential
benefits and success of our new organizational structure and recent
senior management changes; our ability to develop and commercialize
additional pharmaceutical products; manufacturing or quality control
problems, which may damage our reputation for quality production and
require costly remediation; interruptions in our supply chain;
disruptions of our or third party information technology systems or
breaches of our data security; the restructuring of our manufacturing
network, including potential related labor unrest; the impact of
continuing consolidation of our distributors and customers; and
variations in patent laws that may adversely affect our ability to
manufacture our products; our ability to consummate
dispositions on terms acceptable to us; adverse effects of political
or economic instability, major hostilities or terrorism on our
significant worldwide operations; and our ability to successfully bid
for suitable acquisition targets or licensing opportunities, or to
consummate and integrate acquisitions;
-
compliance, regulatory and litigation matters, including: costs and
delays resulting from the extensive governmental regulation to which
we are subject; the effects of reforms in healthcare regulation and
reductions in pharmaceutical pricing, reimbursement and coverage;
potential additional adverse consequences following our resolution
with the U.S. government of our FCPA investigation; governmental
investigations into sales and marketing practices; potential liability
for sales of generic products prior to a final resolution of
outstanding patent litigation; product liability claims; increased
government scrutiny of our patent settlement agreements; failure to
comply with complex Medicare and Medicaid reporting and payment
obligations; and environmental risks; and other factors
discussed in our Annual Report on Form 20-F for the year
ended December 31, 2016 (“Annual Report”), including in the section
captioned “Risk Factors,” and in our other filings with the U.S.
Securities and Exchange Commission, which are available at www.sec.gov
and www.tevapharm.com.
Forward-looking statements speak only as of the date on which they are
made, and we assume no obligation to update or revise any
forward-looking statements or other information contained herein,
whether as a result of new information, future events or otherwise.
You are cautioned not to put undue reliance on these
forward-looking statements.
View source version on businesswire.com: http://www.businesswire.com/news/home/20180115005254/en/
Source: Teva Pharmaceutical Industries Ltd.
Teva Pharmaceutical Industries Ltd.
IR:
United States:
Kevin
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or
Ran Meir, 215-591-3033
or
Israel:
Tomer
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or
PR:
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or
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