Additional data to be presented examining the
safety and tolerability of AUSTEDO during periods of titration and
maintenance
Teva Neuroscience, Inc., an affiliate of Teva Pharmaceutical
Industries Ltd. (NYSE and TASE: TEVA) will present new study data
on AUSTEDO at the International Parkinson and Movement Disorder
Society annual congress (MDS Virtual Congress 2020) and Psych
Congress 2020 Virtual Experience evaluating the long-term efficacy
and safety of AUSTEDO in patients with tardive dyskinesia (TD), and
the safety and tolerability of AUSTEDO during periods of titration
and maintenance in patients with TD.
“Tardive dyskinesia causes involuntarily, uncontrollable
movements, that can have a significant impact on functioning and
emotional well-being of those living with the condition,” said
Daniel McBryan, M.D., Senior Vice President, Head of Global Medical
Affairs and Pharmacovigilance at Teva. “The data being presented
this year deepen our understanding of the risk-benefit profile of
AUSTEDO over the long-term, in patients most severely impacted by
TD, and provides context around the dosing schedule.”
Three Year Efficacy and Safety of AUSTEDO for Treatment of
TD
The open-label extension of the pivotal ARM-TD and AIM-TD
studies evaluated the long-term efficacy and safety of AUSTEDO for
the treatment of TD. Treatment was titrated up to a maximum daily
dose of 48 mg based on control of movements and medication
tolerability and results were evaluated measuring change from
baseline in Abnormal Involuntary Movement Scale (AIMS) scores and
Clinical Global Impression of Change (CGIC). The following outcomes
were recorded:
- At Week 54 (n=249; total daily dose [mean±SE]: 38.7±0.66 mg),
mean change from baseline in AIMS score was -4.8±0.28, and
physician assessments reported 66% of patients met the “much
improved” or “very much improved” scores on the CGIC.
- At Week 106 (n=194; total daily dose: 39.3±0.75 mg), mean
change from baseline in AIMS score was -5.4±0.33, and physician
assessments reported 65% of patients met the “much improved” or
“very much improved” scores on the CGIC.
- At Week 145 (n=160; total daily dose: 39.4±0.83 mg), mean
change from baseline in AIMS score was -6.6±0.37, and physician
assessments reported 73% of patients met the “much improved” or
“very much improved” scores on the CGIC.
No new safety signals were identified in this population that
were inconsistent with the known safety profile of AUSTEDO.
Long-Term Efficacy and Safety of AUSTEDO In Patients Severely
Impacted by TD
A post hoc analysis of the open-label extension portion of the
pivotal ARM-TD and AIM-TD studies evaluated the efficacy of AUSTEDO
in reducing TD in the most severely impacted patients. Using the
upper quartile of baseline AIMS scores from the open-label
extension, two subgroups were defined as having scores >14 or
≤14. At all-time points from Week two to Week 145, change from
baseline in AIMS score was greater in those with baseline AIMS
score >14 versus ≤14 (mean ±SE at Wk 145: -10.9±0.8, -5.1±0.3).
Percent change from baseline in patients with AIMS score >14
reached -59.4%±3.6% versus -55.2%±3.1% for patients with AIMS score
≤14 at Week 145. The percent of patients with ≥50% AIMS reduction
at each visit was 71% in patients with baseline AIMS score >14
versus 64% in patients with AIMS score ≤14 at Week 145.
No new safety signals were identified in this population that
were inconsistent with the known safety profile of AUSTEDO.
Safety and Tolerability of AUSTEDO During Titration and
Maintenance
The study evaluated data from the ARM-TD and AIM-TD studies and
the open-label extension through week 15 to examine the safety and
tolerability of AUSTEDO during titration and maintenance phases of
therapy.
AE Rates for Fixed-Dose AUSTEDO (12
mg-36 mg groups; n=221), Flexible Dose AUSTEDO (n=169) &
Placebo (n=131)
Phase
Dose Type
Overall AEs
Serious AEs
AEs Leading to Discontinuation
Treatment-related AEs
Titration
Fixed
32.4–40.5%
2.7–6.8%
2.7–5.4%
8.1–16.2%
Flexible
49.1%
3.6%
2.4%
31.4%
Placebo
42.7%
4.6%
3.1%
26.7%
Maintenance
Fixed
21.9–28.4%
0–1.4%
0%
8.2–13.5%
Flexible
32.5%
2.4%
1.2%
12.4%
Placebo
25.2%
2.3%
0%
9.9%
Common AEs for Fixed Dose AUSTEDO (12
mg–36 mg groups)
Headache
Diarrhea
Nasopharyngitis
Depression
Hypertensions
Dry Mouth
Titration
2.7–6.8%
1.4–5.4%
1.4–4.1%
0–4.1%
0–4.1%
0–4.1%
Maintenance
0–4.1%
0%
0%
0%
0%
0%
For flexible-dose AUSTEDO, the only common AE during titration
was somnolence (11.2%); there were no common AEs during
maintenance. Rates of specific AEs in titration and maintenance
were (ranges for all groups in both periods: parkinsonism, 0–1.4%;
suicidal ideation, 0–2.7%; akathisia, 0–1.8%; restlessness,
0–1.4%).
Common AEs for Placebo
Somnolence
Headache
Nausea
Fatigue
Dry Mouth
Titration
6.9%
6.1%
5.3%
4.6%
4.6%
Maintenance
0%
0%
0%
0%
0%
All abstracts presented at MDS Virtual Congress 2020 will be
published in the Movement Disorders journal e-supplement and
displayed as an e-poster in the 2020 Virtual Poster. Abstracts at
the Psych Congress 2020 Virtual Experience will be available online
in the virtual exhibit hall.
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.
AUSTEDO® 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 About AUSTEDO®
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 2,400
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 AUSTEDO, 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 commercial success of AUSTEDO;
- our ability to successfully compete in the marketplace,
including: that we are substantially dependent on our generic
products; consolidation of our customer base and commercial
alliances among our customers; the increase in the number of
competitors targeting generic opportunities and seeking U.S. market
exclusivity for generic versions of significant products;
competition for our specialty products, especially COPAXONE®, our
leading medicine, which faces competition from existing and
potential additional generic versions, competing glatiramer acetate
products and orally-administered alternatives; the uncertainty of
commercial success of AJOVY® or AUSTEDO®; competition from
companies with greater resources and capabilities; delays in
launches of new products and our ability to achieve expected
results from investments in our product pipeline; ability to
develop and commercialize biopharmaceutical products; efforts of
pharmaceutical companies to limit the use of generics, including
through legislation and regulations and the effectiveness of our
patents and other measures to protect our intellectual property
rights;
- our substantial indebtedness, which may limit our ability to
incur additional indebtedness, engage in additional transactions or
make new investments, may result in a further downgrade of our
credit ratings; and our inability to raise debt or borrow funds in
amounts or on terms that are favorable to us;
- our business and operations in general, including: uncertainty
regarding the magnitude, duration, and geographic reach of the
COVID-19 pandemic and its impact on our business, financial
condition, operations, cash flows, and liquidity and on the economy
in general; interruptions in our supply chain, including due to
potential effects of the COVID-19 pandemic on our operations and
business in geographic locations impacted by the pandemic and on
the business operations of our customers and suppliers; adequacy of
and our ability to successfully execute and maintain the activities
and efforts related to the measures we have taken or may take in
response to the COVID-19 pandemic and associated costs therewith;
effectiveness of our restructuring plan announced in December 2017;
challenges associated with conducting business globally, including
adverse effects of the COVID-19 pandemic, political or economic
instability, major hostilities or terrorism; our ability to
attract, hire and retain highly skilled personnel; our ability to
develop and commercialize additional pharmaceutical products;
compliance with anti-corruption sanctions and trade control laws;
manufacturing or quality control problems; disruptions of
information technology systems; breaches of our data security;
variations in intellectual property laws; significant sales to a
limited number of customers; our ability to successfully bid for
suitable acquisition targets or licensing opportunities, or to
consummate and integrate acquisitions; our prospects and
opportunities for growth if we sell assets and potential
difficulties related to the operation of our new global enterprise
resource planning (ERP) system;
- compliance, regulatory and litigation matters, including: our
ability to successfully defend against the DOJ criminal charges of
a Sherman Act violations; increased legal and regulatory action in
connection with public concern over the abuse of opioid medications
in the U.S. and our ability to reach a final resolution of the
remaining opioid-related litigation; costs and delays resulting
from the extensive governmental regulation to which we are subject
or delays in governmental processing time including due to modified
government operations due to the COVID-19 pandemic and effects on
product and patent approvals; the effects of reforms in healthcare
regulation and reductions in pharmaceutical pricing, reimbursement
and coverage; governmental investigations into S&M practices;
potential liability for patent infringement; 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;
- other financial and economic risks, including: our exposure to
currency fluctuations and restrictions as well as credit risks;
potential impairments of our intangible assets; potential
significant increases in tax liabilities; and the effect on our
overall effective tax rate of the termination or expiration of
governmental programs or tax benefits, or of a change in our
business; and other factors discussed in our Quarterly Reports on
Form 10-Q for the first and second quarters of 2020 and our Annual
Report on Form 10-K for the year ended December 31, 2019, 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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version on businesswire.com: https://www.businesswire.com/news/home/20200914005022/en/
IR United States Kevin C. Mannix (215) 591-8912
Ran Meir 972 (3) 926-7516 PR United States Doris Li
(973) 265-3752 Israel Yonatan Beker 972 (54) 888 5898
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