-- ALKS 3831 Met Both Co-Primary Endpoints,
Demonstrating a Favorable Weight Profile Compared to Olanzapine
--
-- Company Plans to Submit New Drug Application
(NDA) to U.S. Food and Drug Administration (FDA) in Mid-2019
--
-- Company to Hold Conference Call Today at 8:30 a.m. ET --
DUBLIN, Nov. 29, 2018 /PRNewswire/ -- Alkermes plc
(Nasdaq: ALKS) today announced positive topline results from
ENLIGHTEN-2, a pivotal phase 3 study of ALKS 3831
(olanzapine/samidorphan), an investigational, novel, once-daily,
oral atypical antipsychotic drug candidate for the treatment of
schizophrenia. ENLIGHTEN-2 is the second of two key phase 3 studies
in the ALKS 3831 registration program and was designed to confirm
ALKS 3831's favorable weight profile compared to olanzapine, an
antipsychotic agent with established efficacy but limited in its
clinical use by a high incidence and magnitude of weight gain.
ENLIGHTEN-2 was a multicenter, double-blind, randomized, phase 3
study that evaluated the weight gain profile of ALKS 3831 compared
to olanzapine over six months in 561 patients with stable
schizophrenia. In the study, ALKS 3831 met the pre-specified
co-primary endpoints, demonstrating both a lower mean percent
weight gain from baseline at six months compared to the olanzapine
group (p=0.003) and a lower proportion of patients who gained 10%
or more of their baseline body weight at six months compared to the
olanzapine group (p=0.003). With the successful completion of
ENLIGHTEN-2, Alkermes plans to submit a New Drug Application (NDA)
to the U.S. Food and Drug Administration (FDA) in mid-2019.
In addition to meeting the co-primary endpoints, the study also
met its pre-specified key secondary endpoint, with the ALKS 3831
treatment group demonstrating a lower proportion of patients who
gained 7% or more of their baseline body weight at six months
compared to the olanzapine group (p=0.001). Consistent with the
phase 2 study of ALKS 3831, the weight gain curves for the ALKS
3831 and olanzapine treatment groups began to separate after Week 4
and continued to diverge for the remainder of the study. For the
ALKS 3831 treatment group, weight stabilized at Week 6 and remained
flat for the rest of the six-month treatment period.
"These unequivocal results from ENLIGHTEN-2 provide evidence of
a clinically meaningful, differentiated weight profile for ALKS
3831 compared to olanzapine. Importantly, ALKS 3831 favorably
shifted the weight gain distribution curve compared to olanzapine,
both in terms of mean weight gain and patients experiencing extreme
weight gain," said Craig Hopkinson,
M.D., Chief Medical Officer and Senior Vice President of Medicines
Development and Medical Affairs at Alkermes. "These findings build
on the positive safety and efficacy profile seen throughout the
ENLIGHTEN development program, and underscore the potential of ALKS
3831 to provide an important benefit for people living with
schizophrenia. With these data now in hand, we will meet with the
FDA and plan to submit a New Drug Application in mid-2019."
"Significant unmet patient need remains in schizophrenia despite
the number of treatment options available. A new agent that offers
the robust efficacy of olanzapine but with a favorable weight
profile that stabilizes within weeks of treatment initiation would
be an important and differentiated addition to the treatment
armamentarium for schizophrenia," said Christoph Correll, M.D., Professor of Psychiatry
and Molecular Medicine at Hofstra Northwell School of Medicine.
"People living with schizophrenia deserve treatment options that do
not sacrifice tolerability for efficacy. A new therapeutic option
with the profile demonstrated by ALKS 3831 in this study would be
clinically meaningful for patients and their healthcare
providers."
Detailed results from the study:
- Co-primary endpoint: Mean percent change from baseline
body weight at six months. Patients in the olanzapine treatment
group (n=272) had a 57% higher mean percent weight change at six
months compared to patients receiving ALKS 3831 (n=266), (6.59% for
olanzapine vs. 4.21% for ALKS 3831, p=0.003).
- Co-primary endpoint: Proportion of patients who gained
10% or more of baseline body weight at six months. Patients in the
olanzapine treatment group had two times the risk of gaining 10% or
more of their baseline body weight at six months compared to
patients receiving ALKS 3831. The proportion of patients who gained
10% or more of their baseline body weight was 29.8% for olanzapine
vs. 17.8% for ALKS 3831, (p=0.003).
- Key secondary endpoint: Proportion of patients who
gained 7% or more of baseline body weight at six months. Patients
in the olanzapine treatment group had two times the risk of gaining
7% or more of their baseline body weight at six months compared to
patients receiving ALKS 3831. The proportion of patients who gained
7% or more of their baseline body weight was 42.7% for olanzapine
vs. 27.5% for ALKS 3831, (p=0.001).
- Additional weight analyses. Additional analyses focused on the
proportion of patients who experienced weight gain of at least 2%,
5% and 15% of their baseline body weight at six months. Similar
findings were observed, demonstrating a favorable profile at each
of these weight gain cutoffs for ALKS 3831 compared to
olanzapine.
- Safety. Overall, 64.2% of patients who received ALKS 3831
completed the study, compared to 63.8% of patients who received
olanzapine. The most common adverse events reported in the ALKS
3831 treatment group were weight gain, somnolence and dry mouth.
The most common adverse events reported in the olanzapine treatment
group were weight gain, somnolence and increased appetite. Serious
adverse events occurred in 3.6% of ALKS 3831 patients and 2.5% of
olanzapine patients during the treatment period.
Alkermes expects to submit the results from the ENLIGHTEN-2
study to a peer-reviewed journal for publication and present full
study results, including other endpoints and effects on metabolic
parameters, at an upcoming scientific meeting.
About the ENLIGHTEN-2 Study
ENLIGHTEN-2 was a
multicenter, randomized, double-blind, phase 3 study that evaluated
the weight gain profile of ALKS 3831 compared to olanzapine over
six months in patients with stable schizophrenia. A total of 561
patients were randomized in a 1:1 manner to receive either ALKS
3831 or olanzapine for six months, and the 538 patients who were
dosed and had at least one post-baseline weight assessment were
included in the full study population. The co-primary endpoints of
the ENLIGHTEN-2 study were the percent change from baseline in body
weight at six months and the proportion of subjects with 10% or
more weight gain from baseline at six months. The key secondary
endpoint evaluated the proportion of patients with 7% or more
weight gain from baseline at six months.
All participants who completed the double-blind portion of the
study were eligible to continue in an open-label, long-term safety
study and receive ALKS 3831 for an additional 12 months. The
objective of the extension phase of the study is to assess the
long-term safety, tolerability and durability of effect of ALKS
3831.
Conference Call
Alkermes will host a conference call
today, Nov. 29, 2018, at 8:30 a.m. ET (1:30 p.m.
GMT), to discuss these topline results. The conference call
may be accessed by dialing +1 888 424 8151 for U.S. callers and +1
847 585 4422 for international callers. The conference call ID
number is 6037988. The conference call will also be webcast on the
Investors section of Alkermes' website at www.alkermes.com. The
webcast will be archived on the Investors section of the Alkermes
website for at least 90 days.
About the ENLIGHTEN Clinical Development Program
The
ENLIGHTEN clinical development program for ALKS 3831 comprises two
key studies: a study evaluating the antipsychotic efficacy of ALKS
3831 compared to placebo over four weeks and a study assessing
weight gain with ALKS 3831 compared to olanzapine in patients with
schizophrenia over six months. The program also includes supportive
studies to evaluate the pharmacokinetic and metabolic profile and
long-term safety of ALKS 3831.
Positive topline data from ENLIGHTEN-1, the first key phase 3
study from the ENLIGHTEN development program, were reported in
June 2017. This study evaluated the
antipsychotic efficacy, safety and tolerability of ALKS 3831
compared to placebo over four weeks in 403 patients experiencing an
acute exacerbation of schizophrenia. ENLIGHTEN-1 met its
prespecified primary endpoint, with ALKS 3831 demonstrating
statistically significant reductions from baseline in Positive and
Negative Syndrome Scale (PANSS) scores compared to placebo
(p<0.001). Data from the study also showed that the olanzapine
comparator arm achieved similar improvements from baseline PANSS
scores compared to placebo (p=0.004). The most common adverse
events for both the ALKS 3831 and olanzapine treatment groups were
weight gain, somnolence and dry mouth.
About ALKS 3831
ALKS 3831 is an investigational,
novel, once-daily, oral atypical antipsychotic drug candidate for
the treatment of schizophrenia. ALKS 3831 is composed of
samidorphan, a novel, new molecular entity, co-formulated with the
established antipsychotic agent, olanzapine, in a single bilayer
tablet.
Weight gain is a common and clinically relevant metabolic side
effect of atypical antipsychotic medications, and olanzapine,
commercially available as ZYPREXA®, has one of the
highest incidences and greatest amounts of weight gain among the
widely prescribed products in this class of drugs.1 ALKS
3831 is designed to provide the strong antipsychotic efficacy of
olanzapine and a differentiated safety profile with favorable
weight and metabolic properties.
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,2 with men and women affected equally.
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: timing and expectations
regarding reporting, and submission for publication of, the
ENLIGHTEN-2 study results; the potential therapeutic and commercial
value of ALKS 3831; timing and expectations regarding interactions
with the FDA and submission of an NDA for ALKS 3831; and the
adequacy of the ENLIGHTEN clinical development program to serve as
the basis of an NDA for ALKS 3831 for schizophrenia. The company
cautions 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 an NDA
for ALKS 3831 will be submitted in a timely manner; once an NDA is
submitted, whether the preclinical and clinical results of the ALKS
3831 studies will meet the regulatory requirements for approval by
the FDA; potential changes in cost, scope and duration of the
ENLIGHTEN clinical development and regulatory program; whether ALKS
3831 could be shown ineffective or unsafe during clinical studies;
and those risks and uncertainties described under the heading "Risk
Factors" in the company's Annual Report on Form 10-K for the year
ended Dec. 31, 2017 and in 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. Existing and prospective investors are cautioned not
to place undue reliance on these forward-looking statements, which
speak only as of the date hereof. Except as required by law, the
company disclaims any intention or responsibility for updating or
revising any forward-looking statements contained in this press
release.
ZYPREXA® is a registered trademark of Eli
Lilly & Company.
1Komossa, K. et al. Olanzapine versus other atypical
antipsychotics for schizophrenia. Cochrane Database of
Systematic Reviews. 2010, Issue 3. Art. No.: CD006654.
2National Institutes of Health. Schizophrenia.
Accessed on Nov. 28, 2018 from
http://report.nih.gov/NIHfactsheets/ViewFactSheet.aspx?csid=67&key=S#S.
Alkermes
Contacts:
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For
Investors:
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