Findings published in CNS Drugs from Open-Label
Extension Study Add to Safety and Tolerability Profile Observed in
Earlier Studies
Teva Pharmaceuticals, a U.S. affiliate of Teva Pharmaceutical
Industries Ltd. (NYSE and TASE: TEVA), today announced results from
the ARC-HD (Alternatives for Reducing Chorea in Huntington’s
Disease) trial, an approximately 3-year open-label, single-arm,
2-cohort, multicenter extension study evaluating the safety and
tolerability of long-term treatment with AUSTEDO®
(deutetrabenazine) tablets for chorea associated with Huntington’s
Disease (HD). The ARC-HD study was conducted by Teva in partnership
with the Huntington Study Group (HSG).
ARC-HD results showed that treatment with AUSTEDO had a safety
and tolerability profile comparable with the First-HD randomized,
double-blind, placebo-controlled, 12-week study. In ARC-HD
medication compliance rates were greater than 90% over the ~3 year
open-label extension period. Over this full period, AUSTEDO
improved and maintained chorea control in both the Rollover cohort
and the Switch cohort, as measured by the Unified Huntington’s
Disease Rating Scale (UHDRS) Total Maximal Chorea (TMC) score.1
“These data provide important insight into the long-term use of
deutetrabenazine for the treatment of chorea associated with
Huntington’s disease, which can have a significant functional
impact on people’s lives,” said Samuel Frank, MD, Associate
Professor of Neurology and Director of HDSA Center of Excellence at
Beth Israel Deaconess Medical Center, Boston, and lead author of
the study. “Results of this study add to the safety and
tolerability profile and support deutetrabenazine as a treatment
choice for this progressive condition. We are deeply grateful to
the researchers, patients and their families who played an integral
role in this study.”
The analysis included a total of 119 patients: 82 patients who
completed the randomized, double-blind placebo-controlled First-HD
trial (Rollover cohort), and 37 patients who converted overnight
from a stable tetrabenazine dose to AUSTEDO with subsequent dose
adjustments (Switch cohort). The average mean daily dose of AUSTEDO
at the conclusion of the study was 45.7 mg. The findings were
published online in CNS Drugs.
“Chorea is one of the most striking physical manifestations of
Huntington’s Disease that occurs in approximately 90% of HD
patients,” said Eran Harary, MD, SVP, Global Head of Specialty
R&D at Teva. 2 “As a disease that can have significant
functional impact on patients’ and caregivers’ lives, we’re proud
to share these new data to provide valuable insights for this
community of patients and for those who provide care to them each
day.”
3 Year Safety Results
Exposure-adjusted incidence rates (EAIRs) were used to compare
the frequency of adverse events (AEs) in this long-term open-label
extension study with those in the short-term First-HD study. EAIRs
related to AEs were comparable to those in the pivotal First-HD
trial.
Common AEs (≥4% in either cohort) in the Rollover and Switch
cohorts, respectively, included: fall, depression, anxiety,
insomnia, somnolence, and akathisia. There were no new safety
concerns.
3 Year TMC and Total Motor Score (TMS)
Findings
The study showed that mean TMC scores decreased from baseline to
Week 8 and maintained chorea control through ~3 years.
Key results include:
- In patients who rolled over from the pivotal study, from
baseline to Week 8 there was a:
- 4.5-point reduction in mean chorea scores (SD: 3.1; 95% CI:
–5.2, –3.7);
- 7.1-point reduction in mean TMS (SD: 7.3; 95% CI: –8.8,
–5.5);
- In patients who switched overnight from tetrabenazine, from
baseline to Week 8 there was a:
- 2.1-point reduction in mean chorea scores (SD: 3.3; 95% CI:
–3.1, –1.0).
- 2.4-point reduction in mean TMS (SD: 8.7; 95% CI: –5.4,
0.5).
- Reductions in TMC were maintained for all subjects in both
cohorts from Week 8 to Week 145 (or to the end of treatment,
whichever was earlier; –0.5 [SD: 5.2; 95% CI: –1.9, 1.0]).
HD is a rare and fatal neurodegenerative disorder, affecting
approximately 35,000 people in the United States.3,4 Chorea is
associated with involuntary, random and sudden, twisting and/or
writhing movements and is one of the most striking physical
manifestations of this disease.2 Chorea can interfere with daily
function, cause social isolation, and increase risk of injury,
leading to decreased quality of life for patients with HD.1
About AUSTEDO (deutetrabenazine) Tablets
AUSTEDO is the first and only vesicular monoamine transporter 2
(VMAT2) inhibitor approved by the U.S. Food and Drug Administration
for the treatment of tardive dyskinesia (TD) in adults and for the
treatment of chorea associated with Huntington’s disease. TD is a
movement disorder that is characterized by uncontrollable,
abnormal, and repetitive movements of the face, torso, and/or other
body parts, which may be disruptive and negatively impact
individuals. Chorea – involuntary, random and sudden, twisting
and/or writhing movements – is one of the most striking physical
manifestations of Huntington’s disease and occurs in approximately
90% of patients. Chorea can have a significant impact on daily
activities and progressively limit peoples’ lives. Safety and
effectiveness in pediatric patients have not been established.
Indications and Usage
AUSTEDO (deutetrabenazine) tablets is indicated in adults for
the treatment of chorea associated with Huntington’s disease and
for the treatment of tardive dyskinesia.
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: AUSTEDO may prolong the QT interval,
but the degree of QT prolongation is not clinically significant
when AUSTEDO is administered within the recommended dosage range.
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.
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.
About Huntington Study Group
Founded in 1993, the Huntington Study Group (HSG), a
global not-for-profit organization, together with its wholly owned
for-profit subsidiary, HSG Clinical Research, Inc., designs,
implements, manages, and conducts clinical research trials. The
HSG, a leader in conducting clinical trials for HD, has more than
800 HD experts at over 130 HSG Credentialed Research Sites
worldwide. The mission of the HSG is seeking treatments that make a
difference for those affected by HD. The HSG also offers
educational services like CME4HD™ for healthcare professionals and
care providers on treating patients with HD. For more information,
visit our
website www.huntingtonstudygroup.org.
The ARC-HD study was conducted in cooperation between the HSG
and the Clinical Trials Coordination Center (CTCC) at the
University of Rochester Medical Center's Center for Health +
Technology (CHeT). For more information, visit the CTCC
website https://www.urmc.rochester.edu/health-technology/our-expertise/clinical-trials-coordination.aspx.
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, 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. You
can identify these forward-looking statements by the use of words
such as “should,” “expect,” “anticipate,” “estimate,” “target,”
“may,” “project,” “guidance,” “intend,” “plan,” “believe” and other
words and terms of similar meaning and expression in connection
with any discussion of future operating or financial performance.
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 our ability to develop and commercialize
biopharmaceutical products, competition for our specialty products,
including AUSTEDO, AJOVY® and COPAXONE®; our ability to achieve
expected results from investments in our product pipeline, our
ability to develop and commercialize additional pharmaceutical
products, and the effectiveness of our patents and other measures
to protect our intellectual property rights; our substantial
indebtedness; our business and operations in general, including
uncertainty regarding the COVID-19 pandemic and the governmental
and societal responses thereto; 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; costs and delays resulting from the
extensive pharmaceutical regulation to which we are subject or
delays in governmental processing time due to travel and work
restrictions caused by the COVID-19 pandemic; compliance,
regulatory and litigation matters, including failure to comply with
complex legal and regulatory environments; other financial and
economic risks; and other factors discussed in our Quarterly Report
on Form 10-Q for the second quarter of 2022 and in our Annual
Report on Form 10-K for the year ended December 31, 2021, including
in the section captioned “Risk Factors.” 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.
1 Frank, S. Testa C, Edmondson, M. et al. The Safety of
Deutetrabenazine for Chorea in Huntington Disease: An Open-label
Extension Study. CNS Drugs. 2022. [to be updated upon publication]
2 A Physician’s Guide to the Management of Huntington’s Disease
(3rd edition). Huntington’s Disease Society of America (HDSA)
website. 3 Fisher E, Hayden R. Multisource ascertainment of
Huntington disease in Canada: prevalence and population at risk.;
Mov Disord. 2014;29(1):105-114. 4 Huntington’s disease: a family
guide. HDSA website.
http://hdsa.org/wp-content/uploads/2015/03/HDSA_FamilyGuide.pdf.
Published 2016. Accessed September 2022.
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