DUBLIN and EMERYVILLE, Calif., Aug. 31, 2016 /PRNewswire/ -- Allergan plc
(NYSE: AGN) a leading global pharmaceutical company, today
announced that its subsidiaries Forest Laboratories, LLC, Forest
Laboratories Holdings, Ltd. and Allergan USA, along with Adamas Pharmaceuticals, Inc.
(Nasdaq: ADMS), have entered into a settlement agreement with
Amneal Pharmaceuticals LLC and Amneal Pharmaceuticals of
New York, LLC.
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The settlement relates to a patent infringement litigation
brought by Forest and Adamas in response to Amneal's abbreviated
new drug application (ANDA) seeking approval to market generic
versions of Allergan's NAMZARIC® (memantine and
donepezil hydrochlorides) extended-release, a once-daily,
fixed-dose combination of memantine hydrochloride (a NMDA receptor
antagonist) and donepezil hydrochloride (an acetylcholinesterase
inhibitor, AChEI). It is Allergan's understanding that Amneal is
the first applicant to file an ANDA containing a paragraph IV
certification regarding NAMZARIC®.
This settlement provides additional clarity for the
patent-protected life of NAMZARIC®. Under the
terms of the settlement agreement, and subject to review of the
settlement terms by the U.S. Federal Trade Commission, Forest and
Adamas will grant Amneal a license to market generic versions of
NAMZARIC® beginning on January 1,
2025, following receipt by Amneal of final approval from the
U.S. Food and Drug Administration (FDA) on its ANDA for generic
NAMZARIC®. Alternatively, under certain
circumstances, Amneal has an option to launch an authorized generic
version of NAMZARIC® beginning on January 1, 2026. Other terms of the settlement
were not disclosed.
Similar patent infringement litigation brought by Allergan,
Forest and Adamas against Amerigen Pharmaceuticals, Inc. and
Amerigen Pharmaceuticals Ltd., which have filed an ANDA seeking
approval to market generic versions of NAMZARIC® remains
pending in the U.S. District Court for the District of Delaware.
"Allergan is proud of its commitment to providing therapies and
advancing the development of new treatments that can help the
millions of patients and their caregivers living with Alzheimer's
disease," said Bill Meury, Chief
Commercial Officer, Allergan. "Our recently announced expanded
label for NAMZARIC® allows patients with
moderate-to-severe Alzheimer's disease, who are currently
stabilized on Aricept, to start combination therapy directly with
NAMZARIC®. Approximately 75 percent of patients
diagnosed with Alzheimer's disease are in the moderate-to-severe
stage of the disease and yet only about one-third of these patients
are currently treated with combination therapy."
Allergan is also focused on developing a number of new compounds
for the treatment of Alzheimer's disease, including first-in-class
selective small molecule agonists targeting muscarinic M1 and M4
receptors in the brain.
About NAMZARIC®
NAMZARIC is a
once-daily, fixed-dose combination of memantine hydrochloride, a
NMDA receptor antagonist, and donepezil hydrochloride, an
acetylcholinesterase inhibitor indicated for the treatment of
moderate to severe dementia of the Alzheimer's type in patients
stabilized on 10 mg of donepezil HCl once daily.
Memantine hydrochloride extended-release is the active
ingredient in the currently marketed NAMENDA XR®, which
is indicated for the treatment of moderate to severe dementia of
the Alzheimer's type. Donepezil is the active ingredient in
ARICEPT® (donepezil hydrochloride), which is indicated
for the treatment of mild to severe dementia of the Alzheimer's
type. Allergan and Adamas collaborated on the development of the
fixed-dose combination and Allergan owns the exclusive U.S.
commercialization rights, while Adamas will retain exclusive
commercialization rights outside of the U.S.
IMPORTANT SAFETY INFORMATION
CONTRAINDICATIONS
NAMZARIC is contraindicated in patients with known hypersensitivity
to memantine hydrochloride,donepezil hydrochloride, piperidine
derivatives, or to any excipients used in the formulation.
WARNINGS AND PRECAUTIONS
Anesthesia
NAMZARIC is likely to exaggerate
succinylcholine-type muscle relaxation during anesthesia.
Cardiovascular Conditions
NAMZARIC may have vagotonic effects on the sinoatrial and
atrioventricular nodes manifesting as bradycardia or heart block.
Bradycardia or heart block may manifest in patients both with and
without known underlying cardiac conduction abnormalities. Syncopal
episodes have been reported in association with the use of
donepezil hydrochloride, an active ingredient in NAMZARIC.
Peptic Ulcer Disease and Gastrointestinal Bleeding
Patients treated with NAMZARIC should be monitored closely for
symptoms of active or occult
gastrointestinal bleeding, especially those at increased risk for
developing ulcers, those with a history of ulcer disease, or those
receiving concurrent nonsteroidal anti-inflammatory drugs
(NSAIDs).
Nausea and Vomiting
NAMZARIC can cause diarrhea, nausea, and vomiting. Although in most
cases, these effects have been mild and transient, sometimes
lasting one to three weeks, and have resolved during continued use
of donepezil hydrochloride, patients should be observed closely at
the initiation of treatment.
Genitourinary Conditions
NAMZARIC may cause bladder outflow obstructions. Conditions that
raise urine pH may decrease the urinary elimination of memantine,
an active ingredient in NAMZARIC, resulting in increased plasma
levels of memantine.
Seizures
Cholinomimetics, including donepezil
hydrochloride, are believed to have some potential to cause
generalized convulsions. However, seizure activity also may be a
manifestation of Alzheimer's disease.
Pulmonary Conditions
Cholinesterase inhibitors should be prescribed with care to
patients with a history of asthma or obstructive pulmonary
disease.
ADVERSE REACTIONS
- The most common adverse reactions, occurring at a frequency of
at least 5% in patients taking memantine hydrochloride
extended-release 28 mg/day, and greater than placebo, were headache
(6% vs 5%), diarrhea (5% vs 4%), and dizziness (5% vs 1%).
- The most common adverse reactions, occurring at a frequency of
at least 5% in patients taking donepezil, and at twice or more the
rate of placebo, were diarrhea (10% vs 4%), anorexia (8% vs 4%),
vomiting (8% vs 4%), nausea (6% vs 2%), and ecchymosis (5% vs
2%).
DRUG INTERACTIONS
- Alterations of urine pH toward the alkaline condition may lead
to an accumulation of memantine with a possible increase in adverse
reactions. NAMZARIC should be used with caution under conditions
that may be associated with increased urine pH including
alterations by diet, drugs, and the clinical state of the
patient.
- The combined use of memantine hydrochloride with other NMDA
antagonists (amantadine, ketamine, and dextromethorphan) has not
been systematically evaluated and such use should be approached
with caution.
- Inhibitors of CYP450, 3A4 (eg,
ketoconazole) and 2D6 (eg, quinidine), inhibit donepezil metabolism
in vitro. Whether there is a clinical effect of quinidine is
not known.
- Inducers of CYP3A4 (eg, phenytoin, carbamazepine,
dexamethasone, rifampin, and phenobarbital) could increase the rate
of elimination of donepezil.
- Cholinesterase inhibitors, including donepezil hydrochloride,
have the potential to interfere with the activity of
anticholinergic medications.
- A synergistic effect may be expected when cholinesterase
inhibitors, including donepezil hydrochloride, are given
concurrently with succinylcholine, similar neuromuscular blocking
agents, or cholinergic agonists such as bethanechol.
DOSAGE AND ADMINISTRATION
For patients stabilized on donepezil and not currently on
memantine:
For patients stabilized on donepezil hydrochloride 10 mg and not
currently on memantine hydrochloride, the recommended starting dose
of NAMZARIC is 7 mg/10 mg, taken once a day in the evening. The
dose should be increased in 7 mg increments of the memantine
hydrochloride component to the recommended maintenance dose of 28
mg/10 mg once daily. The minimum recommended interval between dose
increases is one week. The dose should only be increased if the
previous dose has been well tolerated. The maximum dose is 28 mg/10
mg once daily.
For patients with severe renal impairment (creatinine clearance
5-29 mL/min, based on the Cockcroft-Gault equation) stabilized on
donepezil hydrochloride 10 mg once daily and not currently on
memantine hydrochloride the recommended starting dose of NAMZARIC
is 7 mg/10 mg taken once a day in the evening. The dose should be
increased to the recommended maintenance dose of 14 mg/10 mg once
daily in the evening after a minimum of one week.
For patients stabilized on both donepezil and
memantine:
Patients stabilized on memantine hydrochloride (10 mg twice
daily or 28 mg extended-release once daily) and donepezil
hydrochloride 10 mg once daily can be switched to NAMZARIC 28 mg/10
mg, taken once a day in the evening. Patients should start NAMZARIC
the day following the last dose of memantine hydrochloride and
donepezil hydrochloride administered separately.
Patients with severe renal impairment, stabilized on memantine
hydrochloride (5 mg twice daily or 14 mg extended-release once
daily) and donepezil hydrochloride 10 mg once daily, can be
switched to NAMZARIC 14 mg/10 mg, taken once daily in the
evening.
For Full Prescribing Information, visit www.namzaric.com.
About Allergan plc
Allergan plc (NYSE: AGN), headquartered in Dublin, Ireland, is a bold, global
pharmaceutical company and a leader in a new industry model –
Growth Pharma. Allergan is focused on developing,
manufacturing and commercializing branded pharmaceuticals, devices
and biologic products for patients around the world.
Allergan markets a portfolio of leading brands and best-in-class
products for the central nervous system, eye care, medical
aesthetics and dermatology, gastroenterology, women's health,
urology and anti-infective therapeutic categories.
Allergan is an industry leader in Open Science, the Company's
R&D model, which defines our approach to identifying and
developing game-changing ideas and innovation for better patient
care. This approach has led to Allergan building one of the
broadest development pipelines in the pharmaceutical industry with
65+ mid-to-late stage pipeline programs in development.
Our Company's success is powered by our more than 16,000 global
colleagues' commitment to being Bold for Life. Together, we build
bridges, power ideas, act fast and drive results for our customers
and patients around the world by always doing what is right.
With commercial operations in approximately 100 countries,
Allergan is committed to working with physicians, healthcare
providers and patients to deliver innovative and meaningful
treatments that help people around the world live longer, healthier
lives.
For more information, visit Allergan's website at
www.Allergan.com.
About Adamas Pharmaceuticals, Inc.
Adamas Pharmaceuticals, Inc. is driven to improve the lives of
those affected by chronic disorders of the central nervous system.
The company seeks to achieve this by modifying the pharmacokinetic
profiles of approved drugs to create novel therapeutics for use
alone and in fixed-dose combination products. Adamas is currently
developing ADS-5102, its lead wholly-owned product candidate, for
the treatment of levodopa-induced dyskinesia associated with
Parkinson's disease and for the treatment of walking impairment in
patients with multiple sclerosis. The company is also evaluating
ADS-4101, an extended-release version of an FDA-approved
single-agent compound for the treatment of epilepsy. Under a
license agreement with Forest Laboratories Holdings Limited, an
indirect wholly-owned subsidiary of Allergan plc, the company is
eligible to receive royalties from Forest on sales of Namenda
XR® and Namzaric™ beginning in June of 2018 and May of
2020, respectively.
For more information, please visit www.adamaspharma.com.
Forward-Looking Statement
Statements contained in this press release that refer to future
events or other non-historical facts are forward-looking statements
that reflect Allergan's current perspective of existing trends and
information as of the date of this release. Except as expressly
required by law, Allergan disclaims any intent or obligation to
update these forward-looking statements. Actual results may differ
materially from Allergan's current expectations depending upon a
number of factors affecting Allergan's business. These factors
include, among others, the difficulty of predicting the timing or
outcome of FDA approvals or actions, if any; the impact of
competitive products and pricing; market acceptance of and
continued demand for Allergan's products; difficulties or delays in
manufacturing; and other risks and uncertainties detailed in
Allergan's periodic public filings with the Securities and Exchange
Commission, including but not limited to Allergan's Annual Report
on Form 10-K for the year ended December 31,
2015 and Quarterly Report on Form 10-Q for the quarter ended
June 30, 2016 (certain of such
periodic public filings having been filed under the "Actavis plc"
name). Except as expressly required by law, Allergan disclaims any
intent or obligation to update these forward-looking
statements.
CONTACTS:
Allergan:
Investors:
Lisa DeFrancesco
(862) 261-7152
Media:
Mark Marmur
(862) 261-7558
Adamas
Martin
Forrest
(510) 944-1112
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SOURCE Allergan plc; Adamas Pharmaceuticals, Inc.