01.03.2019 | Investors

New Data Published in the International Journal of Neuropsychopharmacology Support that Rapastinel May Produce Rapid and Sustained Antidepressant Effects Through a Potentially Novel Mechanism of Action

Preclinical research demonstrated rapastinel positively modulates the NMDA receptor

DUBLIN, Jan. 3, 2019 /PRNewswire/ -- Allergan plc (NYSE: AGN) today announced new pharmacology research for its investigational compound rapastinel, which is currently being studied in Phase 3 trials for the treatment of major depressive disorder (MDD). Published in the International Journal of Neuropsychopharmacology, the preclinical research supports that rapastinel exhibited rapid and sustained antidepressant effects through positive modulation of the NMDA (N-methyl-D-aspartate) receptor and suggests that it may work differently from NMDA receptor antagonists like ketamine and S-ketamine (esketamine).   

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"Depression treatments for the past 40 years have involved medications affecting the level of monoamines in the brain — serotonin, dopamine, and norepinephrine.   Rapastinel works on the glutamate system representing a completely different mechanistic approach. Our research found that rapastinel acts through a novel site within the NMDA receptor to enhance NMDA receptor function, providing a mechanism of action to explain both the rapid-acting antidepressant effects and a low propensity for dissociative and other psychotomimetic side effects," said John Donello, VP of Research Pharmacology at Allergan and lead author of the study. "We believe rapastinel represents a potentially novel pharmacological approach to treating major depressive disorder."

Glutamate is the most prominent excitatory neurotransmitter in the brain, research suggests that dysfunction of the glutamatergic system may play a role in the neurobiology of MDD. The NMDA receptor is one of the glutamatergic receptors in the brain, and plays a critical role in learning, memory, and the strength of synaptic communication. The current research suggests that rapastinel may help relieve depression by enhancing NMDA receptor function.  

Please see the full publication here: https://academic.oup.com/ijnp/advance-article/doi/10.1093/ijnp/pyy101/5244644 

About Rapastinel 
Rapastinel is positive NMDA receptor modulator that demonstrated a rapid onset of antidepressant effect within one day that was sustained for an average of seven days after a single injection in a Phase 2 clinical study. Rapastinel is currently being evaluated as a once weekly, bolus intravenous (IV) injection in adjunctive and monotherapy MDD in Phase 3 clinical studies. Rapastinel is also being evaluated in MDD patients at imminent risk of suicide in a phase 2 proof of concept study.

About MDD
Approximately 16 million Americans are living with MDD, with 6.7 percent of U.S. adults reporting at least one MDD episode in the past year. MDD is the leading cause of disability in the U.S. for people between the ages of 15 and 44 and the primary reason why someone dies of suicide about every 12 minutes.

There remains a significant unmet need in treating MDD. Upwards of 70 percent of patients with MDD are partial or non-responders to first-line therapies, which include selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs). In addition, current antidepressants can take up to 6-8 weeks to produce a clinically-relevant response, with tolerability issues leading to early discontinuation for many patients. Patients with an inadequate response to current therapies may continue to experience significant depressive symptoms, which can include suicidal ideation in patients with severe, recurrent, or chronic depression. In the U.S. alone, treatment resistant depression costs $29 billion to $48 billion annually in direct health care and indirect work loss-related costs, accounting for a large share of the MDD economic burden.

About Allergan plc
Allergan plc (NYSE: AGN), headquartered in Dublin, Ireland, is a bold, global pharmaceutical leader. Allergan is focused on developing, manufacturing and commercializing branded pharmaceutical, device, biologic, surgical and regenerative medicine 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, a model of research and development, which defines our approach to identifying and developing game-changing ideas and innovation for better patient care. With this approach, Allergan has built one of the broadest development pipelines in the pharmaceutical industry.

Allergan's success is powered by our 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 every day.

For more information, visit Allergan's website at www.Allergan.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 on existing trends and information as of the date of this release. 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; the impact of uncertainty around timing of generic entry related to key products, including RESTASIS®, on our financial results; risks associated with divestitures, acquisitions, mergers and joint ventures; uncertainty associated with financial projections, projected cost reductions, projected debt reduction, projected synergies, restructurings, increased costs, and adverse tax consequences; 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, 2017 and Allergan's Quarterly Report on Form 10-Q for the period ended September 30, 2018. Except as expressly required by law, Allergan disclaims any intent or obligation to update these forward-looking statements.



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