New Data Show Azilect® (rasagiline tablets) Provided Clinical Benefit in
Patients with Early Parkinson’s When Added to Sub-Optimally Controlled
Patients on Dopamine Agonist Therapy
Results Add to Evidence for Azilect as an Effective and Well-Tolerated
Treatment Option at Different Stages of the Progression of Parkinson’s Disease
JERUSALEM -- March 20, 2013
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
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
“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 exemplifies
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 65^th American
Academy of Neurology (AAN) Annual Meeting in San Diego, Calif. on Wednesday,
March 20, 2013. Full data from the study will be submitted for publication.
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
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
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
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,
ABOUT AZILECT^® (EUROPE)
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 women.
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 instituted.
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
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Reform Act of 1995:
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beliefs and expectations of management. Such statements are based on
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and unknown risks and uncertainties that could cause our future results,
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innovative products, especially Copaxone® (including competition from
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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.
Kevin C. Mannix, (215) 591-8912
Kristen Frank, (215) 591-8908
Tomer Amitai, 972 (3) 926-7656
Lundbeck IR Contact:
Simon Mehl Augustesen, +45 36 434980
Teva PR Contacts:
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Denise Bradley, (215) 591-8974
Lundbeck PR Contact:
Mads Kronborg, +45 3643 2851
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