— Orexin 2 Receptor Agonist ALKS 2680
Demonstrated Clinically Meaningful and Statistically Significant
Improvements from Baseline in Mean Sleep Latency Compared to
Placebo at All Doses Tested in Both Narcolepsy Type 2 and
Idiopathic Hypersomnia —
— ALKS 2680 Was Generally Well Tolerated at
All Doses Tested —
— Dose-Dependent Effects and Pharmacodynamic
Profile Support Advancement Into Planned Phase 2 Study
—
DUBLIN, April 9, 2024 /PRNewswire/ -- Alkermes plc
(Nasdaq: ALKS) today announced positive topline results from the
narcolepsy type 2 (NT2) and idiopathic hypersomnia (IH) cohorts of
a phase 1b, proof-of-concept study
evaluating ALKS 2680, the company's novel, investigational, oral
orexin 2 receptor (OX2R) agonist in development as a once-daily
treatment for narcolepsy. ALKS 2680 data demonstrated clinically
meaningful and statistically significant improvements from baseline
in mean sleep latency on the Maintenance of Wakefulness Test (MWT)
compared to placebo at all doses tested. ALKS 2680 was generally
well tolerated in both patient populations at all doses tested.
The phase 1b NT2 (n=9) and IH
(n=8) study cohorts evaluated the safety, tolerability,
pharmacokinetics and pharmacodynamics of ALKS 2680 via once-daily,
single, oral administration. Participants were randomized to a
four-way crossover study in which each participant received 5 mg,
12 mg and 25 mg of ALKS 2680, and placebo, with washout periods
between each treatment. Topline results from each cohort are as
follows:
Narcolepsy Type 2:
- In the nine patients with NT2, treatment with ALKS 2680
demonstrated improved wakefulness compared to placebo at all doses
tested, with a clear dose response. Prior to treatment with ALKS
2680, these patients had baseline sleep latencies ranging from 3 to
33 minutes, with a mean sleep latency of 14 minutes at baseline.
Treatment with ALKS 2680 resulted in statistically significant and
clinically meaningful improvements in sleep latency in these
patients with NT2, with a mean change from baseline versus placebo
of 12 minutes at the 5 mg dose (p<0.05), 19 minutes at the 12 mg
dose (p<0.001), and 21 minutes at the 25 mg dose (p<0.001)
(least squares mean difference). Placebo treatment in this cohort
resulted in no change in mean sleep latency. At the 12 mg and 25 mg
doses, the observed mean MWT scores over an eight-hour period
post-dose were within the reported normal range for healthy
individuals.1
- ALKS 2680 was generally well tolerated across all doses tested
in participants with NT2. All treatment-emergent adverse events
(TEAEs) were transient and self-resolving. TEAEs were mild in
severity, with the exception of one moderate case of pollakiuria at
the highest dose (25 mg). AEs observed in >1 participant with
NT2 and deemed to be related to study drug were pollakiuria,
insomnia and dizziness. One mild, transient occurrence of
photophobia was reported in a single patient at the 25 mg dose,
which self-resolved within two hours of onset.
- There were no serious AEs or AEs leading to discontinuation in
patients with NT2. Additionally, there were no clinically
meaningful, treatment-emergent changes in hepatic and renal
parameters, vital signs, or electrocardiogram (ECG)
parameters.
- The company plans to initiate a phase 2 study in patients with
NT2 in the second half of 2024.
Idiopathic Hypersomnia:
- In the eight patients with IH, treatment with ALKS 2680
demonstrated improved wakefulness compared to placebo at all doses
tested, with a clear dose response. Prior to treatment with ALKS
2680, these patients had baseline sleep latencies ranging from 6 to
34 minutes, with a mean sleep latency of 23 minutes at baseline.
Treatment with ALKS 2680 resulted in statistically significant and
clinically meaningful improvements in sleep latency in these
patients with IH, with a mean change from baseline versus placebo
of 8 minutes at the 5 mg dose (p<0.05), 11 minutes at the 12 mg
dose (p<0.01), and 18 minutes at the 25 mg dose (p<0.001)
(least squares mean difference). Placebo treatment in this cohort
resulted in a two-minute reduction in mean sleep latency. At the 12
mg and 25 mg doses, the observed mean MWT scores over an eight-hour
period post-dose were within the reported normal range for healthy
individuals.1
- ALKS 2680 was generally well tolerated across all doses tested
in participants with IH. All TEAEs were transient and
self-resolving. TEAEs were mild in severity, with the exception of
one moderate case of pollakiuria at the highest dose (25 mg). AEs
observed in >1 participant and deemed to be related to study
drug were pollakiuria, insomnia and dizziness. One mild, transient
occurrence of visual disturbance was reported in a single patient
at the 25 mg dose, which self-resolved approximately one hour after
onset.
- 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 ECG parameters.
"The magnitude and durability of effect of ALKS 2680 seen in
this proof-of-concept study in patients with narcolepsy type 2 and
idiopathic hypersomnia is exciting. These data support further
clinical evaluation of ALKS 2680 and demonstrate that orexin 2
receptor agonists such as ALKS 2680 may have utility in treating
sleep disorders in patients without known orexin deficiency," said
Ron Grunstein, M.D., Ph.D., Head of
Sleep and Circadian Research at the Woolcock Institute of Medical
Research. "New treatment options are needed, and orexin agonists
have the potential to transform the current treatment landscape for
people living with narcolepsy."
"We're pleased to share these topline results in patients with
narcolepsy type 2 and idiopathic hypersomnia, which build upon our
previously disclosed phase 1b data in
narcolepsy type 1. These data further validate our hypothesis that
an orexin agonist with appropriate pharmaceutical properties has
potential to provide significant clinical benefits for both
narcolepsy type 1 and type 2 patient populations," said
Craig Hopkinson, M.D., Chief Medical
Officer and Executive Vice President of Research & Development
at Alkermes. "With these data now in hand, we are moving quickly to
select doses for a phase 2 study in narcolepsy type 2, which we
plan to initiate in the second half of this year."
Alkermes expects to submit results from this phase 1b, proof-of-concept study to a peer-reviewed
journal for publication and to present additional ALKS 2680 study
results at upcoming scientific meetings.
About the ALKS 2680 Phase 1 Study
The phase 1
study for ALKS 2680 included single-ascending dose and
multiple-ascending dose evaluations in healthy volunteers, and
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 ranging from 3 mg to 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 enrolled patients with NT1 (n=10), NT2 (n=9) or IH
(n=8). Following an initial two-week washout period of existing
medications, patients received single doses of three active dose
levels of ALKS 2680 (1 mg, 3 mg and 8 mg for NT1; 5 mg, 12 mg and
25 mg for NT2 and IH) and placebo in a randomized sequence in a
four-way crossover design, with washout periods between each
treatment in the sequence. The objectives were to assess safety and
tolerability, and changes from baseline in average sleep
latency, as measured 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).
About ALKS 2680
ALKS 2680 is a novel, investigational,
oral, selective orexin 2 receptor (OX2R) agonist in development as
a once-daily treatment for 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.2 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 was 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 global
biopharmaceutical company that seeks to develop innovative
medicines in the field of neuroscience. The company has a portfolio
of proprietary commercial products for the treatment of alcohol
dependence, opioid dependence, schizophrenia and bipolar I
disorder, and a pipeline of clinical and preclinical candidates in
development for neurological disorders. Headquartered in
Dublin, Ireland, Alkermes has a
research and development 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; and the company's
expectations regarding plans and timelines for further clinical
development activities for ALKS 2680, including 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, 2023 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 Krahn LE, Arand DL, Avidan AY, et al. Recommended
protocols for the Multiple Sleep Latency Test and the Maintenance
of Wakefulness Test in adults: guidance from the American Academy
of Sleep Medicine. J Clin Sleep Med. 2021;17(12):2489–2498.
2 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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