— Initial ALKS 2680 Data
Demonstrated Dose-Dependent, Significantly Improved Sleep Latency
Compared to Placebo in Narcolepsy Type 1 —
— ALKS 2680 Was Generally
Well Tolerated at All Doses Tested —
— Pharmacokinetic Profile of
ALKS 2680 Supports Once-Daily Dosing and Mimics the Natural
Sleep/Wake Cycle —
— Consistent, Dose-Dependent
Effects Enable Dose Selection for Evaluation in Planned Phase 2
Study —
DUBLIN, Oct. 23, 2023 /PRNewswire/ -- Alkermes plc
(Nasdaq: ALKS) today announced preliminary results, including
initial proof-of-concept data, from a phase 1 study evaluating ALKS
2680, the company's novel, investigational orexin 2 receptor (OX2R)
agonist in development for the treatment of narcolepsy. The ongoing
phase 1 study is evaluating the safety, tolerability,
pharmacokinetics and pharmacodynamics of ALKS 2680 in healthy
volunteers and patients with narcolepsy or idiopathic hypersomnia
via once-daily, oral administration. Initial data from the single-
and multiple-ascending dose evaluations in healthy volunteers and
the first cohort of four patients with narcolepsy type 1 (NT1) will
be presented today at the 2023 World Sleep Congress in Rio de Janeiro.
The patients with NT1 were randomized to a crossover study in
which each of them received 1 mg, 3 mg and 8 mg of ALKS 2680, and
placebo, with washout periods between each treatment. Single
administration of each dose strength of ALKS 2680 achieved
statistically significant, clinically meaningful improvements
compared to placebo in wakefulness, as measured by the maintenance
of wakefulness test (MWT).
In the four patients with NT1, treatment with ALKS 2680
demonstrated improved sleep latency compared to placebo at all
doses tested, with a clear dose response. Following treatment with
ALKS 2680, mean sleep latency in patients improved by 18 minutes,
30 minutes and 37 minutes from mean pre-treatment baseline sleep
latency of three minutes at the 1 mg, 3 mg and 8 mg doses,
respectively (least squares mean). Placebo treatment resulted in a
one-minute reduction in mean sleep latency. The differences between
ALKS 2680 and placebo were statistically significant for all doses:
1 mg (p<0.01), 3 mg (p<0.001), and 8 mg (p<0.001).
Treatment with ALKS 2680 resulted in clinically meaningful
improvements in MWT from baseline at all doses tested. At the 8 mg
dose of ALKS 2680, patients maintained wakefulness for the
full 40-minute MWT duration, up to 10 hours post-dose. MWT scores
at 3 mg were comparable to the 8 mg scores for the first 6 hours
post-dose, and treatment with both the 1 mg and 3 mg doses of ALKS
2680 resulted in improved MWT scores up to 8 hours
post-dose.
ALKS 2680 was generally well tolerated across all doses tested
in the patients with NT1. Drug-related adverse events (AEs) were
seen only at the 8 mg dose and were mild in severity. The AEs
observed in >1 participant and deemed to be treatment-emergent
at the 8 mg dose were insomnia (n=3), pollakiuria (urinary urgency
or frequency) (n=2) and salivary hypersecretion (n=2). There were
no serious AEs or AEs leading to discontinuation. Additionally,
there were no clinically meaningful, treatment-emergent changes in
hepatic and renal parameters, vital signs, or electrocardiogram
(ECG) parameters.
"The early proof-of-concept and safety data we've seen in this
ongoing phase 1 study of ALKS 2680 in both healthy volunteers and
four patients with narcolepsy type 1 are compelling. These data
support further evaluation of ALKS 2680 as a potential treatment
for narcolepsy," said Brendon Yee,
Ph.D., Professor and Respiratory and Sleep Physician at the
Woolcock Institute of Medical Research. "Orexin 2 receptor agonists
such as ALKS 2680 represent an exciting new class of potential
treatments for narcolepsy, with the opportunity to transform the
treatment paradigm for people living with this disease."
In healthy volunteers, ALKS 2680 was evaluated at single- and
multiple-ascending doses. In the single-dose evaluation, ALKS 2680
was dosed from 1 mg to 50 mg. In the multiple-dose evaluation,
participants received single daily doses of ALKS 2680 at 3 mg, 8
mg, 15 mg and 25 mg strengths for up to 10 days. ALKS 2680 was
generally well tolerated across all doses tested and the maximum
tolerated dose was not reached. Most AEs were mild, transient, and
resolved without intervention or treatment interruption. In the
single-ascending dose evaluation, AEs observed in >1 participant
and deemed related to study drug were dizziness, pollakiuria,
nausea and blurred vision, and most occurred at or above the 15 mg
dose level. In the multiple-ascending dose evaluation, AEs observed
in >1 participant and deemed related to study drug were
insomnia, dizziness, pollakiuria and visual disturbances described
as blurred or distorted vision, and most occurred at or above the 8
mg dose. There were no safety signals identified in vital signs,
laboratory parameters or ECGs.
In healthy volunteers, ALKS 2680 was observed to be centrally
active and to have a pharmacokinetic and pharmacodynamic profile
that supports once-daily, oral dosing.
"Narcolepsy is a serious, chronic, neurological disease that
impairs regulation of the sleep-wake cycle and negatively impacts
daily life. There is significant unmet need for people with
narcolepsy, as no currently available treatments address the
underlying biology of the disease: orexin deficiency or
dysfunction," said Craig Hopkinson,
M.D., Chief Medical Officer and Executive Vice President of
Research & Development at Alkermes. "These initial data support
our design rationale for ALKS 2680 as a highly potent, orally
bioavailable, selective orexin 2 receptor agonist designed to
address the underlying pathology of narcolepsy. The consistent and
dose-dependent effects observed in the initial proof-of-concept
data enable dose selection for evaluation in phase 2. We look
forward to sharing additional updates from the phase 1 study, and
plan to initiate our phase 2 study of ALKS 2680, in the first half
of 2024."
About the ALKS 2680 Phase 1 Study
The phase 1
study for ALKS 2680 includes single-ascending dose and
multiple-ascending dose evaluations in healthy volunteers, and a
double-blind, cross-over treatment in patients with narcolepsy type
1 (NT1), narcolepsy type 2 (NT2) and idiopathic hypersomnia
(IH).
In the healthy volunteer phase of the study, each cohort
included eight participants, six of whom were randomized to receive
ALKS 2680 and two of whom received placebo. In the single-dose
portion, ALKS 2680 was dosed from 1 mg to 50 mg. In the
multiple-dose portion, participants received single daily doses of
ALKS 2680 at 3 mg, 8 mg, 15 mg and 25 mg strengths for up to 10
days. The objectives of this part of the study were to assess ALKS
2680's safety, tolerability, pharmacokinetics and
pharmacodynamics.
The phase 1b proof-of-concept part
of the study is enrolling patients with NT1, NT2 or IH, with up to
eight patients for each such indication. Following an initial
two-week washout period of existing medications, patients receive
single doses of three active dose levels of ALKS 2680 and placebo
in a randomized sequence in a four-way crossover design, with
washout periods between each treatment in the sequence. The primary
objectives are to assess safety and tolerability, and changes from
baseline in the average sleep latency through the Maintenance of
Wakefulness Test (MWT) at each cross-over, along with plasma PK,
biomarkers such as quantitative electroencephalogram (qEEG) and
event-related potential (ERP), and a cognitive test, the Sustained
Attention to Response Task (SART). Data from the first four
patients with NT1 will be presented at World Sleep Congress.
About ALKS 2680
ALKS 2680 is a novel, investigational,
oral, selective orexin 2 receptor (OX2R) agonist in development for
the treatment of narcolepsy. Orexin neuropeptides are important
regulators of the sleep/wake cycle through OX2R activation, and
loss of orexinergic neurons in the brain is associated with
excessive daytime sleepiness and cataplexy in
narcolepsy.1 ALKS 2680 was designed to address the
underlying pathology of narcolepsy with the goal of improving
duration of wakefulness and providing cataplexy control. Once-daily
oral administration of ALKS 2680 is currently being evaluated in a
phase 1 study in healthy volunteers and people living with
narcolepsy type 1, narcolepsy type 2 and idiopathic
hypersomnia.
About Alkermes plc
Alkermes plc is a fully-integrated,
global biopharmaceutical company developing innovative medicines in
the fields of neuroscience and oncology. The company has a
portfolio of proprietary commercial products focused on alcohol
dependence, opioid dependence, schizophrenia and bipolar I
disorder, and a pipeline of product candidates in development for
neurological disorders and cancer. Headquartered in Dublin, Ireland, Alkermes has a research and
development (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 potential
therapeutic and commercial value of ALKS 2680 for the treatment of
narcolepsy; the company's expectations regarding plans and
timelines for further clinical development activities for ALKS
2680, including dose selection, initiation of the phase 2 study and
presentation of additional data from the phase 1 study. 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 ALKS
2680 could be shown to be ineffective or unsafe; whether
preclinical and initial clinical results for ALKS 2680 will be
predictive of results of further clinical studies or real-world
results; potential changes in the cost, scope and duration of the
ALKS 2680 development program; whether future clinical trials or
future stages of ongoing clinical trials for ALKS 2680 will be
initiated or completed on time or at all; 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, 2022 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.
1 Nagahara T, Saitoh T, Kutsumura N, Irukayama-Tomobe Y,
Ogawa Y, Kuroda D, Gouda H, Kumagai H, Fujii H, Yanagisawa M,
Nagase H. Design and Synthesis of Non-Peptide, Selective Orexin
Receptor 2 Agonists. J Med Chem. 2015 Oct 22;58(20):7931-7. doi:
10.1021/acs.jmedchem.5b00988. Epub 2015 Aug 26. PMID:
26267383.
Alkermes Contacts:
For Investors: Sandy Coombs, +1 781 609 6377
For Media: Gretchen Murphy, +1 781 609 6419
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