DUBLIN--(BUSINESS WIRE)--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-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 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 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 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 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 a manufacturing facility in 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 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).
