Alkermes plc, a fully integrated, global biopharmaceutical company, has initiated the pivotal clinical development programme for ALKS 5461, a once-daily, oral investigational medicine with a novel mechanism of action for the adjunctive treatment of major depressive disorder (MDD). The comprehensive pivotal programme, named FORWARD (Focused On Results With A Rethinking of Depression), includes a total of 12 studies, including three core phase 3 efficacy studies and nine supportive studies.

The first FORWARD study, evaluating the onset of clinical effect, safety and tolerability of ALKS 5461 in approximately 60 patients with MDD, has begun, and the three core efficacy studies are expected to begin in mid 2014.

The FORWARD pivotal programme will evaluate the safety and efficacy of ALKS 5461 in patients suffering from MDD who have had an inadequate response to commonly prescribed drugs, including selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs). Alkermes expects to use safety and efficacy data from the FORWARD studies as the basis for a New Drug Application (NDA) to be submitted to the US Food and Drug Administration (FDA), pending study results.

“With a novel mechanism of action and Fast Track designation from the FDA, ALKS 5461 is designed to offer a new treatment option for the millions of people with MDD with urgent unmet medical needs,” stated Elliot Ehrich, M.D., Chief Medical Officer of Alkermes. “The comprehensive FORWARD programme incorporates state-of-the-art design elements for depression trials and will be conducted in collaboration with leading clinical investigators.”

The FORWARD (Focused On Results With A Rethinking of Depression) pivotal program for ALKS 5461 will include three core phase 3 efficacy studies, as well as nine supportive studies to evaluate the long-term safety, dosing, pharmacokinetic profile and human abuse liability of ALKS 5461. The three core efficacy studies will utilize state-of-the-art methodologies to reduce the impact of clinically meaningful placebo response and are expected to randomize a total of approximately 1,500 patients with MDD who have had an inadequate response to standard therapies. The primary efficacy endpoint for the three core efficacy studies will be the change from baseline in Montgomery–Åsberg Depression Rating Scale (MADRS) scores.

In April 2013, Alkermes announced positive data from a phase 2 randomized, double-blind, multicenter, placebo-controlled study of ALKS 5461 in 142 patients with MDD who had an inadequate response to a stable dose of either an SSRI or an SNRI. Data from the study showed that ALKS 5461 was generally well tolerated and significantly reduced depressive symptoms across a range of standard measures, including the Hamilton Depression Rating Scale (HAM-D17) (p=0.026), MADRS (p=0.004) and the Clinical Global Impression – Severity Scale (CGI-S) (p=0.035).

ALKS 5461 is a proprietary investigational oral medicine for the treatment of MDD. ALKS 5461 has a novel mechanism of action in the treatment of depressive symptoms based on modulation of the opioid system in the brain, employing a balanced combination of agonist and antagonist components that act on opioid receptors, and includes a novel opioid modulator, samidorphan, discovered by Alkermes. Samidorphan was formerly referred to as ALKS 33. In October 2013, the FDA granted Fast Track status for ALKS 5461 for the adjunctive treatment of MDD in patients with an inadequate response to standard therapies.

According to the DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition), major depressive disorder (MDD) is a condition in which patients exhibit depressive symptoms, such as a depressed mood or a loss of interest or pleasure in daily activities consistently for at least a two-week period, and demonstrate impaired social, occupational, educational or other important functioning. An estimated 16.1 million people in the U.S. suffer from MDD in a given year, the majority of whom may not adequately respond to initial antidepressant therapy.

Alkermes plc is a fully integrated, global biopharmaceutical company that applies its scientific expertise and proprietary technologies to develop innovative medicines that improve patient outcomes.