-- Neither Study Met Primary Endpoint; Additional Analyses of FORWARD-4 Provide Supportive Evidence of Efficacy --
-- Third Efficacy Study, FORWARD-5, Will Recruit Additional Patients; Data May Provide Regulatory Path Forward for ALKS 5461 --
FORWARD-4 tested two dose levels of ALKS 5461 (2mg/2mg and 0.5mg/0.5mg)
compared to placebo. 385 patients entered the study. There was a clear
trend toward efficacy with the 2mg/2mg dose of ALKS 5461 on the primary
endpoint, and post hoc analyses achieved statistical significance for
the entire 2mg/2mg dose group on the MADRS endpoint. Based on these
FORWARD-3 tested ALKS 5461 (2mg/2mg) compared to placebo. 429 patients entered the study. Placebo response was greater than that observed in FORWARD-4 and no treatment effect of ALKS 5461 was observed. Negative trials due to significant placebo effect are not uncommon in the study of major depressive disorder.
FORWARD-5, the third pivotal efficacy study in the FORWARD program, is
ongoing, testing two dose levels of ALKS 5461 (2mg/2mg and 1mg/1mg).
FORWARD-5 shares common design and analysis features with FORWARD-4.
Based on information gained from FORWARD-3 and FORWARD-4, patient
enrollment in FORWARD-5 will be increased and the statistical analysis
plan will be updated.
In the case of a clear positive outcome for FORWARD-5,
“We are gaining important insights as we proceed with the FORWARD
program for ALKS 5461. The third pivotal efficacy study, FORWARD-5, is
ongoing and we plan to adapt it to incorporate findings from FORWARD-3
and FORWARD-4,” stated Elliot Ehrich, M.D., Chief Medical Officer of
“We are steadfast in our commitment to developing new medicines for
serious CNS conditions where there is a clear and compelling need for
new treatment options for patients and their families,” said Richard
Pops, Chief Executive Officer of
In FORWARD-3, the most commonly reported adverse events were nausea, headache and fatigue, and in FORWARD-4 they were nausea, headache and dizziness. The safety and tolerability profile of ALKS 5461 was consistent with that reported for the phase 2 and FORWARD-1 studies.
About FORWARD-3 and FORWARD-4
FORWARD-3 and FORWARD-4 are phase 3, randomized, double-blind, multicenter, placebo-controlled studies that evaluated the safety, tolerability and efficacy of once-daily ALKS 5461 as adjunctive treatment in patients with MDD who had an inadequate response to a stable dose of either a selective serotonin reuptake inhibitor (SSRI) or a serotonin-norepinephrine reuptake inhibitor (SNRI). The prespecified primary endpoint of both studies was the change from baseline in MADRS scores. All participants in the double-blind portion of the study were eligible to continue in an open-label phase and receive ALKS 5461 for an additional 12 months.
About the Phase 3 FORWARD Clinical Program
The FORWARD (Focused On Results With A Rethinking of Depression) pivotal program for ALKS 5461 includes three core phase 3 efficacy studies, as well as additional supportive studies to evaluate the long-term safety, dosing, pharmacokinetic profile and human abuse potential of ALKS 5461. The primary efficacy endpoint for the three core efficacy studies is the change from baseline in Montgomery–Åsberg Depression Rating Scale (MADRS) scores.
Further information about the FORWARD studies can be found at www.clinicaltrials.gov.
About ALKS 5461
ALKS 5461 is a proprietary, oral investigational medicine that acts as a balanced neuromodulator in the brain and represents a novel mechanism of action for treating MDD. ALKS 5461 consists of samidorphan and buprenorphine, and is designed to rebalance brain function that is dysregulated in the state of depression. In
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 17 million people in the U.S. suffer from MDD in a given year,1,2 the majority of whom may not adequately respond to initial antidepressant therapy.3
Note Regarding Forward-Looking Statements
Certain statements set forth in this press release constitute “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, but not limited to, statements concerning: the therapeutic value, development and regulatory plans, and commercial potential of ALKS 5461. You are cautioned that forward-looking statements are inherently uncertain. Although the company believes that such statements are based on reasonable assumptions within the bounds of its knowledge of its business and operations, the forward-looking statements are neither promises nor guarantees and they are necessarily subject to a high degree of uncertainty and risk. Actual performance and results may differ materially from those projected or suggested in the forward-looking statements due to various risks and uncertainties. These risks and uncertainties include, among others: whether preclinical and clinical results for ALKS 5461 will be predictive of future clinical study results; whether future clinical trials for ALKS 5461 will be completed on time or at all; potential changes in cost, scope and duration of the ALKS 5461 clinical development program; whether ALKS 5461 could be shown ineffective or unsafe during clinical studies; whether the preclinical and clinical results of ALKS 5461 will meet the regulatory requirements for approval; whether regulatory submissions may occur or are submitted in a timely manner; and those risks described in the
DSM-5® is a registered trademark of the
1 Kessler RC, Chiu WT, Demler O, Walters EE. Prevalence, severity, and comorbidity of twelve-month DSM-IV disorders in the National Comorbidity Survey Replication (NCS-R). Archives of General Psychiatry, 2005 Jun; 62 (6): 617-27.
2 U.S. Census.
3 Rush AJ et al (2007) Am J. Psychiatry 163:11, pp. 1905-1917 (STAR*D Study).
Eva Stroynowski, +1-781-609-6823
Jennifer Snyder, +1-781-609-6166