DUBLIN, March 6, 2019 /PRNewswire/ -- Allergan plc (NYSE: AGN) today announced topline results from three pivotal studies of rapastinel as an adjunctive treatment of Major Depressive Disorder (MDD). In three acute studies (RAP-MD-01,-02,-03), the rapastinel treatment arms did not differentiate from placebo on the primary and key secondary endpoints. In all three acute studies rapastinel was well tolerated without any signal of psychotomimetic side effects. In addition, an interim analysis of the rapastinel relapse prevention study (RAP-MD-04) suggests the primary and key secondary endpoints will not be met.
"We are deeply disappointed with these results, and they are a vivid reminder that drug development is extremely challenging, especially in mental health. We are grateful to the patients, their caregivers, and the investigators who supported these clinical studies. We remain committed to the development of new life changing medications to combat the rising global toll of mental illness," said David Nicholson, Chief Research & Development Officer at Allergan. "We will evaluate the impact of these data on the ongoing monotherapy MDD program and suicidality in MDD study. We expect to make a decision on these programs during the course of 2019."
"As the number of deaths from suicide, alcohol and drugs continue to rise, it is clear that we need effective new approaches for mental illness. We thank Allergan for its long-standing commitment and investment in this important, yet difficult area," said Michael R. Liebowitz MD, Professor of Clinical Psychiatry, Columbia University, Managing Director, The Medical Research Network in New York City.
These Phase 3 adjunctive MDD trials evaluated the efficacy, safety and tolerability of rapastinel, compared to placebo, both in combination with antidepressant therapy (ADT) in patients with MDD who had a partial response to ADT. In all three pivotal clinical trials rapastinel was well tolerated and demonstrated a safety and tolerability profile similar to placebo.
Patients who completed the acute trials were eligible to enter the relapse prevention trial (RAP-MD-04). An interim analysis of (RAP-MD-04) was conducted of the primary and secondary efficacy endpoints of all randomized patients in the double-blind treatment period. At the time of the analysis, all patients had completed all visits relevant for determining a relapse.
Detailed results from these studies will be presented at future scientific meetings.
Study Overview RAP-MD-01,-02,-03
Studies RAP-MD-01 (N= 457) and RAP-MD-03 (N= 415) were randomized, double blind, placebo controlled, multicenter, parallel group Phase 3 clinical trials conducted in the United States, in which 450 mg of rapastinel or placebo were evaluated as an adjunctive treatment to an oral antidepressant in patients with MDD. Study medication was given once weekly as a bolus intravenous injection in addition to an oral ADT, to which the patient had experienced inadequate clinical response.
Study RAP-MD-02 (N= 638) was very similar in design, the main difference being the inclusion of a third treatment arm, in which a dose of 225 mg rapastinel was evaluated.
Patients who completed 3 weeks of double-blind treatment were eligible to enter the (RAP-MD-04) maintenance study, alternatively they were to be followed for 1 week in a safety follow-up period.
Eligible patients for study participation were 18 to 65 years of age and met Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for MDD, with a current major depressive episode of at least 8 weeks and not exceeding 18 months in duration. In addition, eligible patients had experienced no more than partial response (< 50% improvement) to ongoing treatment with an ADT, administered at a stable and adequate (labeled) dose. Patients were required to continue their oral ADT throughout the entire study at a stable dose.
Rapastinel has recently been characterized as a modest and selective positive NMDA receptor modulator with a unique pharmacological mechanism of action fundamentally different from ketamine. In a series of preclinical experiments rapastinel directly enhanced NMDAR activity through a novel site independent of the glycine co-agonist site, and single doses resulted in rapid and sustained antidepressant effects as well as increased synaptic plasticity (Please see the full publication here: https://academic.oup.com/ijnp/advance-article/doi/10.1093/ijnp/pyy101/5244644 ). In a previously conducted Phase 2 clinical study rapastinel demonstrated a rapid onset of antidepressant effect within one day, which continued for approximately seven days after a single injection.
About Rapastinel Clinical Program
In addition to the adjunctive MDD program Allergan is conducting a global Phase 3 monotherapy program evaluating the efficacy, safety and tolerability of rapastinel compared to placebo. These trials are actively recruiting patients.
Allergan is also conducting a Phase 2 proof of concept suicidality study evaluating efficacy, safety and tolerability of rapastinel, compared to placebo in addition to standard of care (SOC) of patients with MDD at imminent risk of suicide.
According to the World Health Organization (WHO) depression is a common disorder with currently 300 million people of all ages affected globally. The WHO lists depression as the leading cause of disability worldwide and as a major contributor to the overall global burden of disease, constituting the leading cause of disability worldwide. 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.
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 primarily focused on four key therapeutic areas including medical aesthetics, eye care, central nervous system and gastroenterology.
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.
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; risks related to impairments; 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, 2018. Except as expressly required by law, Allergan disclaims any intent or obligation to update these forward-looking statements.