–– Treatment With
–– Data From Second Three-Month Period Extend Findings From First Three Months of Treatment and Provide First Evidence of Beneficial Weight Effect for Patients Switching From Olanzapine to ALKS 3831 ––
–– Company on Track to Initiate Pivotal Development Program in 2015 ––
“This second three-month stage of the phase 2 study provided further
confirmation of the positive weight effects and strong efficacy of ALKS
3831 for the treatment of schizophrenia over the complete six-month
study and provided exciting new data relating to patients switching from
olanzapine,” said
For patients who received ALKS 3831 throughout the entire six-month treatment period, efficacy, as evaluated by the reduction from baseline in Positive and Negative Syndrome Scale (PANSS) total scores, was equivalent to olanzapine during the initial three-month stage and this efficacy was maintained throughout the second three-month stage (change in PANSS total score from Week 12 to Week 24 was -1.7 points, 95% confidence interval (CI): (-2.7, -0.7)). The beneficial effect on weight gain observed during the initial three months was also maintained during the second three-month stage. Mean percent change in body weight, from Week 12 to Week 24, was 0.5%, 95% CI: (-0.2%, 1.2%), indicating a consistent and durable blockade of olanzapine-induced weight gain.
Patients who received olanzapine in the initial three-month stage were transitioned to receive ALKS 3831 for the second three-month stage. For these patients, efficacy as evaluated by PANSS scores was maintained (change in PANSS total score from Week 12 to Week 24 was -1.3 points, 95% CI: (-3.3, 0.7)). During the initial three-month stage, this patient population experienced significant weight gain, consistent with previously reported studies of olanzapine (mean percent change in body weight from baseline was 4.3%, 95% CI: (2.4%, 6.2%)). When these patients were transitioned to ALKS 3831 in the second three-month stage, overall no further weight gain was observed (mean percent change in body weight from Week 12 to Week 24 was 0.1%, 95% CI: (-1.0%, 1.2%)).
ALKS 3831 was generally well tolerated in the six-month study. For the
initial three-month, active-controlled stage of the study, the most
common adverse events in the ALKS 3831 treatment groups relative to
olanzapine were somnolence, sedation and dizziness.
Phase 2 Study Design
The six-month randomized, multicenter, dose-ranging phase 2 study consisted of two three-month stages. The initial three-month stage was a double-blind, active-controlled study designed to assess the efficacy, safety and tolerability of ALKS 3831, as well as evaluate the impact of ALKS 3831 on weight and other metabolic factors in comparison to olanzapine alone in adult patients with stable schizophrenia. A total of 309 patients were randomized in the study, and the 300 patients who had at least one post baseline PANSS assessment were included in the full study population. In the study, following a one-week oral lead-in of olanzapine, patients were randomly assigned to treatment with olanzapine or one of three different doses of ALKS 3831 (olanzapine + 5 mg, 10 mg or 20 mg samidorphan) for a period of three months. The primary efficacy endpoint of the initial three-month stage of the phase 2 study was the change from baseline at Week 12 in PANSS total score, to assess equivalence of ALKS 3831 to olanzapine using a Mixed-Effect Model Repeated Measure (MMRM) model. Secondary endpoints evaluated the effects of ALKS 3831 on weight gain and other metabolic factors.
Following the completion of the initial three-month stage, patients who received ALKS 3831 continued on the same dose, and patients in the olanzapine group were assigned in a double-blind fashion to ALKS 3831 20 mg for an additional three months. The objective of the second three-month stage was to assess the safety and long-term durability of effect of ALKS 3831 on PANSS total scores and attenuation of weight gain. A total of 187 patients completed the six-month treatment period.
About ALKS 3831
ALKS 3831 is a proprietary, investigational medicine designed as a broad-spectrum antipsychotic for the treatment of schizophrenia. ALKS 3831 is composed of samidorphan, a novel, potent mu-opioid antagonist, in combination with the established antipsychotic drug, olanzapine. ALKS 3831 is designed to attenuate olanzapine-induced metabolic side effects, including weight gain, in patients with schizophrenia and to have utility in the treatment of schizophrenia in patients with alcohol use.
The ALKS 3831 comprehensive phase 2 clinical program is comprised of two
separate studies, including this study focused on the attenuation of
weight gain associated with olanzapine. Weight gain is a common and
clinically relevant metabolic side effect of atypical antipsychotic
medications, and olanzapine has one of the highest incidences and
greatest amounts of weight gain among the widely prescribed products in
this class of drugs.1 The second phase 2 study, initiated in
About Schizophrenia
Schizophrenia is a chronic, severe and disabling brain disorder. The disease is marked by positive symptoms (hallucinations and delusions) and negative symptoms (depression, blunted emotions and social withdrawal), as well as by disorganized thinking. An estimated 2.4 million American adults have schizophrenia,3 with men and women affected equally. Worldwide, it is estimated that one person in every 100 develops schizophrenia, which is one of the most serious types of mental illness.
About
Alkermes plc is a fully integrated, global biopharmaceutical company
developing innovative medicines for the treatment of central nervous
system (CNS) diseases. The company has a diversified commercial product
portfolio and a substantial clinical pipeline of product candidates for
chronic diseases that include schizophrenia, depression, addiction and
multiple sclerosis. Headquartered in
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
plans and commercial potential of ALKS 3831. 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 expressed or implied 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 3831 will be predictive of future clinical study
results; whether ongoing or future clinical trials for ALKS 3831 will be
initiated or completed on time or at all; potential changes in cost,
scope and duration of the ALKS 3831 clinical development program;
whether ALKS 3831 could be shown ineffective or unsafe during clinical
studies; and those risks described in the
1Komossa K, Rummel-Kluge C, Hunger H, Schmid F, Schwarz S, Duggan L, Kissling W, Leucht S. Olanzapine versus other atypical antipsychotics for schizophrenia. Cochrane Database of Systematic Reviews. 2010, Issue 3. Art. No.: CD006654.
2Regier D, Farmer M, Rae D, Locke B, Keith S, Judd L, Goodwin F. Comorbidity of Mental Disorders With Alcohol and Other Drug Abuse. JAMA. 1990, 264: 2511-2518.
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Source:
Alkermes plc
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