-- 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 --
Alkermes plc (NASDAQ: ALKS) today announced preliminary topline
results from FORWARD-3 and FORWARD-4, the first two of three phase
3 efficacy studies to read out from the comprehensive FORWARD
pivotal program for ALKS 5461, a once-daily, oral investigational
medicine with a novel mechanism of action for the adjunctive
treatment of major depressive disorder (MDD) in patients who have
an inadequate response to standard therapies for clinical
depression. Neither of the two studies met the prespecified
primary efficacy endpoint, which compared ALKS 5461 to placebo on
the change from baseline on the Montgomery–Åsberg Depression Rating
Scale (MADRS).
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 analyses, Alkermes believes that
FORWARD-4 provides supportive evidence of the efficacy of ALKS 5461
in the treatment of major depressive disorder.
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. Alkermes will
provide an update later this quarter on the projected timing of
completion of FORWARD-5.
In the case of a clear positive outcome for FORWARD-5, Alkermes
believes that the evidence provided by it and the previously
completed successful, randomized, placebo-controlled phase 2 study,
together with supportive evidence from FORWARD-4, collectively
could provide substantial evidence of efficacy for ALKS 5461 for
the adjunctive treatment of MDD. In that case, Alkermes would
request a meeting with the U.S. Food and Drug Administration’s
(FDA) Division of Psychiatric Products to discuss the regulatory
path for this Fast Track designated medicine.
“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 Alkermes. “Clinical trials of new
medicines for the treatment of major depressive disorder are
complicated by significant placebo response. We designed the
FORWARD pivotal program to include three efficacy studies as we
recognize that this is a challenging disease state where multiple
clinical studies and expansive analyses are generally necessary to
confirm the efficacy of a new medicine.”
“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 Alkermes. “Major
depressive disorder is one of these conditions. We are building a
large body of evidence supporting our belief in the clinical
utility and the novel mechanism of action of ALKS 5461. We await
the results of FORWARD-5 and will determine our next steps along
the regulatory path with those results in hand.”
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-4FORWARD-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
ProgramThe 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 5461ALKS 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
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 antidepressant therapies.
About MDDAccording 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
About AlkermesAlkermes 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 a
manufacturing facility in Wilmington, Ohio. For more information,
please visit Alkermes’ website at www.alkermes.com.
Note Regarding Forward-Looking
StatementsCertain 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 Alkermes plc Quarterly Report on Form
10-Q for the period ended Sept. 30, 2015 and 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.
DSM-5® is a registered trademark of the American Psychiatric
Association.
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).
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Alkermes plcFor Investors:Eva Stroynowski, +1-781-609-6823orFor
Media:Jennifer Snyder, +1-781-609-6166
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