Allergan plc., a leading global pharmaceutical company, announced that its phase III ready investigational medication rapastinel (GLYX-13) received Breakthrough Therapy designation from the US Food and Drug Administration (FDA) for adjunctive treatment of Major Depressive Disorder (MDD). This follows the Fast Track designation for rapastinel granted by the FDA in 2014.
"Rapastinel is the first Allergan medicine to be granted Breakthrough Therapy designation by the FDA, underscoring our commitment to innovative research and development that addresses significant unmet medical needs. Breakthrough Therapy designation will allow us to work more closely with the FDA to bring this important therapy to patients as rapidly as possible," said David Nicholson, executive vice president and president of global R&D brands at Allergan. "There remains an unmet medical need for agents in depression that demonstrate a rapid onset of action. We believe that rapastinel has great potential to fulfill that unmet medical need in major depressive disorder."
The Breakthrough Therapy designation was based on preclinical and preliminary clinical evidence for rapastinel, which supports a rapid (within 1 day) and sustained antidepressant effect over the course of the phase II studies. Rapastinel has been found to be well tolerated in studies to date, with no psychotomimetic or hallucinogenic side effects observed.
"Nonresponse to antidepressants is a key reason that major depressive disorder is one of the United States' leading public health problems and there is a great need for new therapies that are truly different from those that are currently used," said Dr. Michael E. Thase, Professor of Psychiatry, Perelman School of Medicine of the University of Pennsylvania and the Corporal Michael J. Crescenz Veterans Affairs Medical Center in Philadelphia, Pennsylvania. "Rapastinel thus has great promise because it works through a different pathway than conventional antidepressants and may even work faster than standard therapies."
Enacted as part of the 2012 FDA Safety and Innovation Act (FDASIA), Breakthrough Therapy designation is intended to expedite the development and review of a potential new medicine if it is intended to treat a serious or life-threatening disease and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies. The Breakthrough Therapy designation is distinct from FDA's other mechanisms to expedite drug development and review.
Allergan plans to initiate phase 3 studies of rapastinel in 2016.
Rapastinel is an investigational intravenous formulation of a novel NMDA receptor partial agonist, which is being evaluated for adjunctive treatment of MDD, and has shown a rapid onset of antidepressant efficacy 1 day after a single dose in a phase 2 clinical trial of patients with MDD who had an inadequate response to one or more antidepressants. No psychotomimetic or hallucinogenic side effects were observed with rapastinel. A series of phase 3 registration trials are planned to begin in 2016. Rapastinel was granted Fast Track designation by the FDA in 2014.
Approximately 16 million Americans are living with MDD. There remains a significant unmet need in treating MDD. Upwards of 70 per cent of patients with MDD are partial or non-responders to first-line therapies which include SSRIs and SNRIs. Additionally, the STAR*D trial reported that only 33 per cent of patients reported remission of their MDD symptoms after monotherapy with an SSRI. In patients that do respond to an SSRI, numerous clinical trials have shown that it can take anywhere from 2 to 6 weeks for a patient perceive and report that their depressive symptoms are improving. During these first 2 to 6 weeks of traditional monoamine-based therapy, patients may continue to experience significant depressive symptoms, which can include suicidal ideation in patients with severe, recurrent, or chronic depression.