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.
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.
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
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
NAMZARIC is likely to exaggerate succinylcholine-type muscle relaxation during anesthesia.
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.
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.
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.
Cholinesterase inhibitors should be prescribed with care to patients with a history of asthma or obstructive pulmonary disease.
- 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%).
- 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.
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.
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SOURCE Allergan plc; Adamas Pharmaceuticals, Inc.