Teva Pharmaceutical Industries Ltd. (NYSE: TEVA) and H. Lundbeck A/S
announced today that a double-blind, placebo controlled, randomized,
multicenter study of Azilect® (rasagiline tablets) met its
primary endpoint. The study, known as ANDANTE (Add oN to Dopamine
AgoNists in the TrEatment of Parkinson’s
disease), assessed the efficacy and tolerability of Azilect as add-on
treatment to dopamine agonists compared to placebo. While the efficacy
of Azilect as adjunct to levodopa has been established in previous
studies (leading to its indication as adjunct therapy to levodopa), its
efficacy in combination with dopamine agonist monotherapy has not
previously been studied.
Results from the study demonstrated that the addition of Azilect 1mg/day
provided a statistically significant improvement (Primary endpoint:
treatment effect ± SE -2.4 ± 0.95 [95% CI -4.3,-0.5, p=0.012]) in total
Unified Parkinson’s Disease Rating Scale (UPDRS) score (Parts I, II and
III, version three) from baseline to week 18 in patients sub-optimally
controlled with dopamine agonist monotherapy compared to placebo.
Azilect was well-tolerated with no significant difference in adverse
events compared to placebo.
“The positive outcome of this study is important news for the PD
community, for patients and physicians,” said Robert A. Hauser, M.D.,
M.B.A., Director, Parkinson’s Disease & Movement Disorders Center at the
University of South Florida and primary investigator of the study. “In
addition to rasagiline providing symptomatic benefit to patients
sub-optimally controlled with dopamine agonist monotherapy, the study
confirmed that rasagiline is well-tolerated and provided
proof-of-concept for adding rasagiline to dopamine agonist therapy.”
As a monoamine oxidase B (MAO-B) inhibitor, Azilect acts by increasing
available synaptic dopamine. This mode of action provided the rationale
for add-on therapy to dopamine agonists in the management of PD.
“The ANDANTE data continue to clarify the clinical profile of Azilect
and the role it plays in helping to meet the needs of those living with
PD, at multiple points in the progression of their disease,” said Dr.
Michael Hayden, President of Global R&D and Chief Scientific Officer at
Teva Pharmaceutical Industries Ltd. “Teva is committed to the continued
research and understanding of Azilect in PD and to sharing important
findings like these with the scientific community.”
“We are pleased with the results of the study as they reinforce the
efficacy and tolerability profile we’ve seen in the clinical development
programme for Azilect,” said Anders Gersel Pedersen, Executive Vice
President, Research & Development at H. Lundbeck A/S. “ANDANTE
Lundbeck’s long-term commitment to championing treatment advances that
meet the specific needs of the CNS communities we serve, including
patients, healthcare providers, care partners and advocates.”
The results of the study will be presented today as part of the Emerging
Science program (formerly known as Late-Breaker Science) at the 65th
American Academy of Neurology (AAN) Annual Meeting in San Diego, Calif.
on Wednesday, March 20, 2013. Full data from the study will be submitted
ANDANTE was an 18-week, double-blind, placebo controlled, randomized,
multi-center study assessing the safety and clinical benefit of
rasagiline compared to placebo as add-on therapy to stable dose of
dopamine agonists (DAs) in the treatment of early PD.
In addition to the above stated primary endpoint results, data from the
secondary endpoint analysis showed the addition of Azilect®
resulted in a statistically significant improvement in the UPDRS motor
examination subscale (Part III) (p=0.007). There were no significant
differences between groups for the UPDRS activities of daily living
(ADL) (p=0.301) or CGI-I scores. Azilect was well-tolerated in the study.
ANDANTE was conducted at 50 research sites in the United States. A total
of 328 patients on sub-optimal DA monotherapy randomized into the study
to add-on treatment with Azilect (N=163) or placebo (N=165). Volunteers
returned to the clinic at nine weeks for an interim visit and again at
18 weeks, for an end of study visit.
To be enrolled patients needed to be on a stable DA monotherapy for ≥ 30
days. Patients included could not receive an optimal therapeutic dose of
DAs due to intolerable side effects or were no longer experiencing
sufficient control of their PD symptoms and required an additional
therapeutic agent. Rescue treatment with levodopa was allowed once the
patient had started treatment with study drug and had completed four
weeks of treatment. DA therapy could not be adjusted during the study.
The side effect profile of Azilect as add-on to DA therapy was evaluated
for changes in nature and frequency of dopaminergic adverse events.
ABOUT AZILECT® (UNITED STATES)
AZILECT® (rasagiline tablets) is indicated for the treatment
of the signs and symptoms of Parkinson's disease (PD) both as initial
therapy alone and to be added to levodopa later in the disease.
Patients should not take AZILECT® if they are taking
meperidine, tramadol, methadone, propoxyphene, dextromethorphan, St.
John’s wort, cyclobenzaprine, or other monoamine oxidase inhibitors
(MAOIs), as it could result in a serious reaction. Patients should
inform their physician if they are taking, or planning to take, any
prescription or over-the-counter drugs, especially antidepressants and
ciprofloxacin. Patients with moderate to severe liver disease should not
take AZILECT®. Patients should not exceed a dose of 1 mg per
day of AZILECT® in order to prevent a possibly dangerous
increase in blood pressure.
Side effects seen with AZILECT® alone are flu syndrome, joint
pain, depression, and indigestion; and when taken with levodopa are
uncontrolled movements (dyskinesia), accidental injury, weight loss, low
blood pressure when standing, vomiting, anorexia, joint pain, abdominal
pain, nausea, constipation, dry mouth, rash, abnormal dreams, and fall.
See additional important information at http://www.azilect.com/Resources/PDFs/PrescribingInformation-pdf.aspx.
For hardcopy releases, please see enclosed full prescribing information.
AZILECT® is currently available in more than 40 countries
worldwide, including the U.S., Canada, Israel, Mexico, and all EU
countries. Teva has a long-term agreement for the joint development and
marketing of AZILECT® in Europe and some additional markets
with H. Lundbeck A/S. In North America, AZILECT® is marketed
by Teva's wholly-owned subsidiary, Teva Neuroscience, Inc. (www.tevaneuro.com).
AZILECT® is indicated for the treatment of idiopathic
Parkinson’s disease (PD) as monotherapy (without levodopa) or as adjunct
therapy (with levodopa) in patients with end of dose fluctuations.
Hypersensitivity to the active substance or to any of the excipients.
Concomitant treatment with other monoamine oxidase (MAO) inhibitors
(including medicinal and natural products without prescription e.g. St.
John's Wort) or pethidine. At least 14 days must elapse between
discontinuation of rasagiline and initiation of treatment with MAO
inhibitors or pethidine. Rasagiline is contraindicated in patients with
severe hepatic impairment.
Special Warnings and Precautions:
The concomitant use of rasagiline and fluoxetine or fluvoxamine should
be avoided. At least five weeks should elapse between discontinuation of
fluoxetine and initiation of treatment with rasagiline. At least 14 days
should elapse between discontinuation of rasagiline and initiation of
treatment with fluoxetine or fluvoxamine. The concomitant use of
rasagiline and dextromethorphan or sympathomimetics such as those
present in nasal and oral decongestants or cold medicinal product
containing ephedrine or pseudoephedrine is not recommended. During the
clinical development program, the occurrence of cases of melanoma
prompted the consideration of a possible association with rasagiline.
The data collected suggests that Parkinson’s disease, and not any
medicinal products in particular, is associated with a higher risk of
skin cancer (not exclusively melanoma). Any suspicious skin lesion
should be evaluated by a specialist. Caution should be used when
initiating treatment with rasagiline in patients with mild hepatic
impairment. Rasagiline use in patients with moderate hepatic impairment
should be avoided. In case patients progress from mild to moderate
hepatic impairment, rasagiline should be stopped.
Rasagiline must not be administered along with other MAO inhibitors
(including medicinal and natural products without prescription e.g. St.
John's Wort) as there may be a risk of non-selective MAO inhibition that
may lead to hypertensive crisis. Serious adverse reactions have been
reported with the concomitant use of pethidine and MAO inhibitors
including another selective MAO-B inhibitor. The concomitant
administration of rasagiline and pethidine is contraindicated. With MAO
inhibitors there have been reports of medicinal product interactions
with the concomitant use of sympathomimetic medicinal products.
Therefore, in view of the MAO inhibitory activity of rasagiline,
concomitant administration of rasagiline and sympathomimetics such as
those present in nasal and oral decongestants or cold medicinal
products, containing ephedrine or pseudoephedrine. Concomitant
administration of rasagiline and dextromethorphan is not recommended.
The concomitant use of rasagiline and fluoxetine or fluvoxamine should
be avoided. Serious adverse reactions have been reported with the
concomitant use of SSRIs, SNRIs, tricyclic/ tetracyclic antidepressants
and MAO inhibitors in clinical trials. Therefore, in view of the MAO
inhibitory activity of rasagiline, antidepressants should be
administered with caution.
Fertility, Pregnancy and Lactation:
No clinical data on exposed pregnancies is available. Animal studies do
not indicate direct or indirect harmful effects with respect to
pregnancy, embryonal/foetal development, parturition or postnatal
development. Caution should be exercised when prescribing to pregnant
Monotherapy: In parentheses is the adverse reaction incidence (%
of patients) in rasagiline vs. placebo, respectively. Adverse reactions
with at least 2% difference over placebo are: Influenza (4.7% vs.
0.7%), depression (5.4% vs. 2%), headache (14.1% vs. 11.9%),
conjunctivitis (2.7% vs. 0.7%), rhinitis (3.4% vs. 0.7%),
dermatitis (2.0% vs. 0%), musculoskeletal pain (6.7%
vs. 2.6%), neck pain (2.7% vs. 0%,), malaise (2% vs. 0%). Adjunct
Therapy: In parentheses is the adverse reaction incidence (% of
patients) in rasagiline vs. placebo, respectively. Adverse reactions
with at least 2% difference over placebo are: Dyskinesia (10.5% vs.
6.2%), orthostatic hypotension (3.9% vs. 0.8%), abdominal
pain (4.2% vs. 1.3%), constipation (4.2% vs. 2.1%), nausea
and vomiting (8.4% vs. 6.2%), decreased weight (4.5% vs. 1.5%).
There is no specific antidote. In case of overdose, patients should be
monitored and the appropriate symptomatic and supportive therapy
For further information, please consult the EU Summary of Product
Characteristics or contact your local Lundbeck subsidiary.
Teva Pharmaceutical Industries Ltd. (NYSE: TEVA) is a leading global
pharmaceutical company, committed to increasing access to high-quality
healthcare by developing, producing and marketing affordable generic
drugs as well as innovative and specialty pharmaceuticals and active
pharmaceutical ingredients. Headquartered in Israel, Teva is the world's
leading generic drug maker, with a global product portfolio of more than
1,000 molecules and a direct presence in about 60 countries. Teva's
branded businesses focus on CNS, oncology, pain, respiratory and women's
health therapeutic areas as well as biologics. Teva currently employs
approximately 46,000 people around the world and reached $20.3 billion
in net revenues in 2012.
About H. Lundbeck A/S
Lundbeck is a global pharmaceutical company highly committed to
improving the quality of life of people living with brain diseases. For
this purpose, Lundbeck is engaged in the entire value chain throughout
research, development, production, marketing and sales of
pharmaceuticals across the world. The company’s products are targeted at
disorders such as depression and anxiety, psychotic disorders, epilepsy,
Huntington’s, Alzheimer’s and Parkinson’s diseases. Lundbeck’s pipeline
consists of several mid- to late- stage development programs.
Lundbeck employs more than 5,800 people worldwide, 2,000 of whom are
based in Denmark. We have employees in 57 countries, and our products
are registered in more than 100 countries. We have research centers in
Denmark, China and the United States and production facilities in Italy,
France, Mexico, China and Denmark. Lundbeck generated revenue of
approximately DKK 15 billion in 2012. For additional information, we
encourage you to visit our corporate site www.lundbeck.com.
Teva's Safe Harbor Statement under the U. S. Private Securities
Litigation Reform Act of 1995:
This release contains forward-looking statements, which express the
current beliefs and expectations of management. Such statements are
based on management’s current beliefs and expectations and involve a
number of known and unknown risks and uncertainties that could cause our
future results, performance or achievements to differ significantly from
the results, performance or achievements expressed or implied by such
forward-looking statements. Important factors that could cause or
contribute to such differences include risks relating to: our ability to
develop and commercialize additional pharmaceutical products,
competition for our innovative products, especially Copaxone® (including
competition from innovative orally-administered alternatives, as well as
from potential purported generic equivalents), competition for our
generic products (including from other pharmaceutical companies and as a
result of increased governmental pricing pressures), competition for our
specialty pharmaceutical businesses, our ability to achieve expected
results through our innovative R&D efforts, the effectiveness of our
patents and other protections for innovative products, decreasing
opportunities to obtain U.S. market exclusivity for significant new
generic products, our ability to identify, consummate and successfully
integrate acquisitions, the effects of increased leverage as a result of
recent acquisitions, the extent to which any manufacturing or quality
control problems damage our reputation for high quality production and
require costly remediation, our potential exposure to product liability
claims to the extent not covered by insurance, increased government
scrutiny in both the U.S. and Europe of our agreements with brand
companies, potential liability for sales of generic products prior to a
final resolution of outstanding patent litigation, including that
relating to the generic version of Protonix®, our exposure to currency
fluctuations and restrictions as well as credit risks, the effects of
reforms in healthcare regulation and pharmaceutical pricing and
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reporting and payment obligations, governmental investigations into
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biotechnology-based products, adverse effects of political or economical
instability, corruption, major hostilities or acts of terrorism on our
significant worldwide operations, interruptions in our supply chain or
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or to attract additional executive and managerial talent, the impact of
continuing consolidation of our distributors and customers, variations
in patent laws that may adversely affect our ability to manufacture our
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impairments of intangible assets and goodwill, potential increases in
tax liabilities, the termination or expiration of governmental programs
or tax benefits, environmental risks and other factors that are
discussed in our Annual Report on Form 20-F for the year ended December
31, 2012 and in our other filings with the U.S. Securities and Exchange
Commission. Forward-looking statements speak only as of the date on
which they are made and the Company undertakes no obligation to update
or revise any forward-looking statement, whether as a result of new
information, future events or otherwise.