Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA) today
announced the Phase 2/3 ARTISTS 1 and Phase 3 ARTISTS 2 trials
designed to evaluate deutetrabenazine compared to placebo for the
treatment of tics in pediatric patients with moderate to severe
Tourette Syndrome failed to meet the primary endpoint of reduction
in motor and phonic tics as assessed by the Total Tic Score of the
Yale Global Tic Severity Scale (YGTSS-TTS).
In the data received this week, the most commonly reported
adverse event in the ARTISTS 1 and ARTISTS 2 studies were headache,
somnolence and fatigue. In this population, no new safety signals
were identified that were inconsistent with the known safety
profile of deutetrabenazine.
“The results of the trials are disappointing, especially as
there is such an unmet need for this community of pediatric
patients,” said Dr. Hafrun Fridriksdottir, Executive Vice
President, Global R&D, at Teva. “As we assess a path forward,
Teva is especially grateful to the investigators, patients and
families who contributed to these studies for such an important
patient population.”
The studies were conducted in partnership between Teva and
Nuvelution Pharma, Inc.
Deutetrabenazine was approved by the FDA as AUSTEDO®
(deutetrabenazine) tablets for the treatment of chorea associated
with Huntington’s disease in April 2017 and for tardive dyskinesia
in adults in August 2017.
About ARTISTS 1
The ARTISTS 1 study was a multicenter, randomized, double-blind,
placebo-controlled, Phase 2/3 study to evaluate the safety,
tolerability and efficacy of deutetrabenazine in 119 pediatric
patients (6-16 years) with moderate to severe Tourette Syndrome.
Patients received either deutetrabenazine or placebo using a 1:1
randomization over 12 weeks of dosing. The primary endpoint was the
change in the Total Tic Score of the Yale Global Tic Severity Scale
(YGTSS-TTS) from baseline to week 12 between placebo and active
treatment groups.
About ARTISTS 2
The ARTISTS 2 study was a multicenter, randomized, double-blind,
placebo-controlled, Phase 3 study to evaluate the safety,
tolerability and efficacy of deutetrabenazine in 158 pediatric
patients (6-16 years) with moderate to severe Tourette Syndrome.
Patients received either deutetrabenazine (low dose or high dose)
or placebo using a 1:1:1 randomization over eight weeks of dosing.
The primary endpoint was the change in the Total Tic Score of the
Yale Global Tic Severity Scale (YGTSS-TTS) from baseline to week
eight between placebo and active treatment groups.
About Tourette Syndrome
Tourette Syndrome is a neurodevelopmental disorder with onset
before age 18 years, characterized by motor and phonic tics that
persist for greater than one year. Symptoms of Tourette Syndrome
typically occur first in early childhood, with peak severity around
the age of 10 years. Most individuals with Tourette Syndrome
experience improvement of symptoms in late adolescence and into
adulthood.
About AUSTEDO® (deutetrabenazine)
AUSTEDO® is a vesicular monoamine transporter 2 (VMAT2)
inhibitor approved by the U.S. Food and Drug Administration for the
treatment of tardive dyskinesia in adults and for the treatment of
chorea associated with Huntington’s disease. Safety and
effectiveness in pediatric patients have not been established.
Indications and Usage
AUSTEDO® is indicated for the treatment of chorea associated
with Huntington’s disease and for the treatment of tardive
dyskinesia in adults.
Important Safety Information
Depression and Suicidality in Patients with Huntington’s
Disease: AUSTEDO® can increase the risk of depression and
suicidal thoughts and behavior (suicidality) in patients with
Huntington’s disease. Balance the risks of depression and
suicidality with the clinical need for treatment of chorea.
Closely monitor patients for the emergence or worsening of
depression, suicidality, or unusual changes in behavior. Inform
patients, their caregivers, and families of the risk of depression
and suicidality and instruct them to report behaviors of concern
promptly to the treating physician. Exercise caution when treating
patients with a history of depression or prior suicide attempts or
ideation. AUSTEDO® is contraindicated in patients who are suicidal,
and in patients with untreated or inadequately treated
depression.
Contraindications: AUSTEDO® is contraindicated in
patients with Huntington’s disease who are suicidal, or have
untreated or inadequately treated depression. AUSTEDO® is also
contraindicated in: patients with hepatic impairment; patients
taking reserpine or within 20 days of discontinuing reserpine;
patients taking monoamine oxidase inhibitors (MAOIs), or within 14
days of discontinuing MAOI therapy; and patients taking
tetrabenazine (Xenazine®) or valbenazine (Ingrezza®).
Clinical Worsening and Adverse Events in Patients with
Huntington’s Disease: AUSTEDO® may cause a worsening in mood, cognition,
rigidity, and functional capacity. Prescribers should periodically re-evaluate
the need for AUSTEDO® in their patients by assessing the effect on
chorea and possible adverse effects.
QTc Prolongation: Tetrabenazine, a closely related VMAT2
inhibitor, causes an increase in the corrected QT (QTc) interval. A
clinically relevant QT prolongation may occur in some patients
treated with AUSTEDO® who are CYP2D6 poor metabolizers or are
co-administered a strong CYP2D6 inhibitor. Dose reduction may be
necessary. The use of AUSTEDO® in combination with other drugs
known to prolong QTc may result in clinically significant QT
prolongations. For patients requiring AUSTEDO® doses greater than
24 mg per day who are using AUSTEDO® with other drugs known to
prolong QTc, assess the QTc interval before and after increasing
the dose of AUSTEDO® or the other drugs. AUSTEDO® should be avoided
in patients with congenital long QT syndrome and in patients with a
history of cardiac arrhythmias.
Neuroleptic Malignant Syndrome (NMS), a potentially fatal symptom complex reported
in association with drugs that reduce dopaminergic transmission,
has been observed in patients receiving tetrabenazine. The risk may
be increased by concomitant use of dopamine antagonists or
antipsychotics. The management of NMS should include immediate
discontinuation of AUSTEDO®; intensive symptomatic treatment and medical
monitoring; and treatment of any concomitant serious medical
problems.
Akathisia, Agitation, and Restlessness: AUSTEDO® may
increase the risk of akathisia, agitation, and restlessness. The
risk of akathisia may be increased by concomitant use of dopamine
antagonists or antipsychotics. If a patient develops akathisia, the
AUSTEDO® dose should be reduced; some patients may require
discontinuation of therapy.
Parkinsonism: AUSTEDO® may cause parkinsonism in patients
with Huntington’s disease or tardive dyskinesia. Parkinsonism has
also been observed with other VMAT2 inhibitors. The risk of
parkinsonism may be increased by concomitant use of dopamine
antagonists or antipsychotics. If a patient develops parkinsonism,
the AUSTEDO® dose should be reduced; some patients may require
discontinuation of therapy.
Sedation and Somnolence: Sedation is a common
dose-limiting adverse reaction of AUSTEDO®. Patients should not
perform activities requiring mental alertness, such as operating a
motor vehicle or hazardous machinery, until they are on a
maintenance dose of AUSTEDO® and know how the drug affects them.
Concomitant use of alcohol or other sedating drugs may have
additive effects and worsen sedation and somnolence.
Hyperprolactinemia: Tetrabenazine elevates serum
prolactin concentrations in humans. If there is a clinical
suspicion of symptomatic hyperprolactinemia, appropriate laboratory
testing should be done and consideration should be given to
discontinuation of AUSTEDO®.
Binding to Melanin-Containing Tissues: Deutetrabenazine or its metabolites bind to
melanin-containing tissues and could accumulate in these tissues
over time. Prescribers should be aware of the possibility of
long-term ophthalmologic effects.
CYP2D6 Metabolism: In patients who are poor CYP2D6
metabolizers or are taking strong CYP2D6 inhibitors, the total
daily dosage of AUSTEDO® should not exceed 36 mg (maximum single
dose of 18 mg).
Common Adverse Reactions: The most common adverse
reactions for AUSTEDO® (>8% and greater than placebo) in a
controlled clinical study in patients with Huntington’s disease
were somnolence, diarrhea, dry mouth, and fatigue. The most common
adverse reactions for AUSTEDO® (4% and greater than placebo) in
controlled clinical studies in patients with tardive dyskinesia
were nasopharyngitis and insomnia.
Please see accompanying full Prescribing Information,
including Boxed Warning.
About Teva
Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA) has
been developing and producing medicines to improve people’s lives
for more than a century. We are a global leader in generic and
specialty medicines with a portfolio consisting of over 3,500
products in nearly every therapeutic area. Around 200 million
people around the world take a Teva medicine every day, and are
served by one of the largest and most complex supply chains in the
pharmaceutical industry. Along with our established presence in
generics, we have significant innovative research and operations
supporting our growing portfolio of specialty and biopharmaceutical
products. Learn more at 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 results of two registration trials of
deutetrabenazine in pediatric patients with Tourette Syndrome,
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:
- challenges inherent in product research and development,
including uncertainty of clinical trials;
- our ability to successfully compete in the marketplace,
including the uncertainty of commercial success of AUSTEDO®;
and other factors discussed in our Annual Report on Form 10-K
and subsequently filed reports, including in the sections captioned
"Risk Factors” and “Forward Looking Statements.” 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.
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IR Contacts United States Kevin C. Mannix (215)
591-8912
Ran Meir 972 (3) 926-7516
PR Contacts United States Doris Li
973-295-7563
Israel Yonatan Beker 972 (54) 888 5898
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