— Novel Mechanism Represents New Treatment Approach for Patients With Inadequate Response to Conventional Antidepressants —
“The magnitude of effect seen with ALKS 5461 in this study is highly
significant. These results are very encouraging for ALKS 5461 as a
potential new treatment approach, with substantial reductions in
depressive symptoms demonstrated and rapid onset of action observed,”
stated
The phase 2 study of ALKS 5461 utilized a sequential parallel comparison design (SPCD), designed to reduce the impact of clinically meaningful response to treatment with placebo. The study included two four-week, randomized, double-blind stages run in sequence: an Initial Study Stage and a Successive Study Stage. The Successive Study Stage randomized only those patients who were non-responders to placebo in the Initial Study Stage. Both stages of the phase 2 study evaluated two doses of ALKS 5461, a lower dose and a higher dose. Overall, the combined analysis of both doses at both stages showed statistically significant efficacy on multiple endpoints compared to placebo. Overall, the lower dose showed greater efficacy than the higher dose and, as a result, will be the top end of the dose range employed in future studies. Results for the lower dose from the Successive Study Stage of the study included:
- ALKS 5461 significantly reduced Hamilton Depression Rating Scale (HAM-D17) scores from baseline (p=0.013), with a reduction of 5.3 points, compared to a reduction of 1.2 points in the placebo group at the end of the four-week treatment period. ALKS 5461 also significantly reduced Montgomery–Åsberg Depression Rating Scale (MADRS) scores from baseline (p=0.004), with a reduction of 8.7 points, compared to a reduction of 1.8 points in the placebo group at the end of the four-week treatment period.
- ALKS 5461 had an onset of effect, as measured by MADRS, evident after one week of treatment.
In the phase 2 results for the overall study population, including both the Initial Study Stage and the Successive Study Stage, patients who received either dose of ALKS 5461 for a treatment period of four weeks showed a significant reduction in depressive symptoms from baseline in HAM-D17 (p=0.026) and MADRS (p=0.004) scores, compared to placebo. The primary endpoint of the phase 2 study was the change from baseline in depressive symptoms over a four-week treatment period in the overall study population, as measured by HAM-D17, compared to placebo. Data from the study showed that ALKS 5461 was generally well tolerated. The most common adverse events observed in the study were nausea, headache and dizziness.
“ALKS 5461 reflects a new approach to the treatment of major depressive
disorder based on modulation of the opioid system in the brain. With
these compelling data in hand, we are planning to meet with the U.S.
Study Design
This phase 2, randomized, double-blind, multicenter, placebo-controlled study assessed the efficacy and safety of once-daily ALKS 5461 as adjunctive treatment in 142 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). Two doses of ALKS 5461 were evaluated, each with a 1:1 ratio of buprenorphine and ALKS 33 (lower dose of 2mg/2mg and higher dose of 8mg/8mg). The primary endpoint of the study was the change from baseline in depressive symptoms over a four-week treatment period, as measured by HAM-D17. Secondary endpoints included additional analyses of patient responses based on HAM-D17, MADRS and Clinical Global Impression – Severity Scale (CGI-S) scores.
The study utilized a sequential parallel comparison design (SPCD), a
design developed ten years ago by Drs. Fava and Schoenfeld at
About ALKS 5461
ALKS 5461 is a proprietary investigational medicine with a novel
mechanism for the treatment of major depressive disorder (MDD). The
mechanism of action for ALKS 5461 in the treatment of depressive
symptoms is based on modulation of the opioid system in the brain,
employing a balanced combination of agonism and antagonism of opioid
receptors. ALKS 5461 consists of buprenorphine, a partial agonist, and
ALKS 33, a potent mu-opioid antagonist, and is designed to be a
once-daily, non-addictive medicine. Early clinical development of ALKS
5461 was funded through a grant from the
About MDD
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,1,2 the majority of whom may not adequately respond to initial antidepressant therapy.3
About
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, including, but not limited to
statements concerning: the therapeutic value of ALKS 5461; the clinical
development of ALKS 5461, including meetings with regulatory authorities
and the product’s clinical development timeline; and the timing of the
company’s planned presentation of phase 2 data 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 the company will initiate a pivotal development
program for ALKS 5461; 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; 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).
Source:
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or
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Jennifer Snyder,
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