–– Treatment With Once-Daily, Oral
Antipsychotic Candidate Demonstrated Durability of Efficacy for
Treatment of Schizophrenia Symptoms and Beneficial Weight Effect
Over Six Months ––
–– 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 ––
Alkermes plc (NASDAQ: ALKS) today announced positive topline
results from the complete, six-month, randomized, dose-ranging
phase 2 study of ALKS 3831, an investigational, novel, oral
atypical antipsychotic drug candidate designed to be a
broad-spectrum treatment for schizophrenia. The study was designed
in two stages: for the initial three months, patients were
randomized to receive olanzapine or one of three doses of ALKS
3831, and antipsychotic efficacy and weight gain were assessed.
Positive topline data from this stage were announced in January
2015, showing that ALKS 3831 met the study’s primary endpoint,
demonstrating antipsychotic efficacy equivalent to olanzapine, as
well as key secondary endpoints showing ALKS 3831’s favorable
effects on weight gain compared to olanzapine. For the second three
months, all patients who received ALKS 3831 during the initial
three months continued to receive ALKS 3831, and patients who had
received olanzapine were switched to ALKS 3831. Data from the
completed study support and extend the initial positive results
showing ALKS 3831’s favorable efficacy and mean weight gain profile
and show for the first time that switching patients from olanzapine
to ALKS 3831 resulted in a cessation of mean weight gain.
“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 Elliot Ehrich, M.D.,
Chief Medical Officer of Alkermes. “ALKS 3831 is a new
antipsychotic designed with the real-world needs of patients in
mind, and introduces a novel and expanded pharmacologic approach to
the treatment of schizophrenia. We look forward to advancing ALKS
3831 into pivotal development later this year, as we work to bring
this medication to the patients and physicians who need new
treatment options for this serious, chronic disease.”
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.
Alkermes will present comprehensive safety and efficacy data from
the phase 2 study at an upcoming medical meeting and submit the
results for publication in a peer-reviewed journal. Alkermes plans
to meet with the U.S. Food and Drug Administration (FDA) for an
End-of-Phase 2 meeting and advance ALKS 3831 into a pivotal
development program in 2015.
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 June 2014, is investigating the
potential utility of ALKS 3831 for the large number of patients
with schizophrenia whose disease is exacerbated by alcohol
use – a group representing over one-third of patients with
schizophrenia.2
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
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 Dublin, Ireland, Alkermes
plc has an R&D center in Waltham, Massachusetts; a
research and manufacturing facility in Athlone, Ireland; and
manufacturing facilities in Gainesville,
Georgia and Wilmington, Ohio. For more information,
please visit Alkermes’ website at www.alkermes.com.
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 Alkermes plc Annual Report on Form 10-K for
the fiscal year ended Dec. 31, 2014, and in other subsequent
filings made by the company with the U.S. Securities and Exchange
Commission (SEC), which are available on the SEC’s website at
www.sec.gov. The information contained in this press release is
provided by the company as of the date hereof, and, except as
required by law, the company disclaims any intention or
responsibility for updating or revising any forward-looking
information contained in this press release.
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.
3National Institutes of Health. Accessed on April 3, 2015 from
http://report.nih.gov/NIHfactsheets/ViewFactSheet.aspx?csid=67&key=S#S.
Alkermes plcFor Investors:Rebecca Peterson, +1 781-609-6378orFor
Media:Jennifer Snyder, +1 781-609-6166
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