— 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 —
— ALKS 2680 Was Generally Well Tolerated at
All Doses Tested —
— Vibrance-1 Phase 2 Study of ALKS 2680 in
Patients With Narcolepsy Type 1 Is Ongoing —
DUBLIN, June 3, 2024 /PRNewswire/ -- Alkermes plc
(Nasdaq: ALKS) today announced new data from the full narcolepsy
type 1 (NT1) cohort 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. The data are
being presented at SLEEP 2024, the 38th annual meeting
of the Associated Professional Sleep Societies (APSS), taking place
June 1-5, 2024 in Houston.
The phase 1b study evaluated the
safety, tolerability, pharmacokinetics and pharmacodynamics of ALKS
2680 via once-daily, single, oral administration. Ten patients
with NT1 were randomized1 to one of four crossover
sequences in which each participant received 1 mg, 3 mg and 8 mg of
ALKS 2680, and placebo, with washout periods between each
treatment. Initial results from the first four patients in this NT1
cohort were previously presented at the 2023 World Sleep
Congress.
"Data from this phase 1b study
provide evidence of a significant treatment effect of single doses
of ALKS 2680 in patients with narcolepsy type 1. In addition,
patients' self-reported measures of alertness further support
continued clinical development of this investigational treatment,
which has the potential to help address significant unmet needs for
people living with excessive daytime sleepiness associated with
narcolepsy," said Ron Grunstein,
M.D., Ph.D., Head of Sleep and Circadian Research at
the Woolcock Institute of Medical Research.
Data highlights from the SLEEP poster presentation (Abstract ID
1323; Poster board 423) include:
Mean Sleep Latency Over 8 Hours:
- In patients with NT1, treatment with ALKS 2680 demonstrated
improved wakefulness compared to placebo at all doses tested, with
a clear dose response.
- Treatment with ALKS 2680 resulted in statistically significant
and clinically meaningful improvements in mean sleep latency on the
Maintenance of Wakefulness Test (MWT), with a mean change from
baseline versus placebo of 18.4 minutes at the 1 mg dose
(p=0.0002), 22.6 minutes at the 3 mg dose (p=0.0001), and 34.0
minutes at the 8 mg dose (p≤0.0001) (least squares mean
difference). Placebo treatment resulted in an approximately 1.4
minute reduction in mean sleep latency from baseline. Prior to
treatment with ALKS 2680, these patients had a mean sleep latency
on the MWT of approximately six minutes at
baseline.2
- At the 3 mg and 8 mg doses, the observed mean MWT scores over
an eight-hour period post-dose were within the reported normal
range for healthy individuals.3
Patient-Reported Alertness on the Karolinska Sleepiness Scale
(KSS):
- The KSS is a subjective measure of self-reported alertness over
the past five minutes, using a nine-point scale (with 1 being
"extremely alert"; 9 being "extremely sleepy"; and 5 being "neither
alert nor sleepy"). Change from baseline on KSS was an exploratory
endpoint.
- ALKS 2680 demonstrated clinically meaningful, dose-dependent
improvements in self-reported alertness in patients with NT1. The
average self-reported score at baseline was approximately 7. ALKS
2680 showed improvements of 2 to 3 points in self-reported
alertness between 1 and 8 hours, indicating clinically meaningful
improvements (p<0.001 at all dose levels vs. placebo).
Safety:
- ALKS 2680 was generally well tolerated across all doses tested
in patients with NT1. Most treatment-emergent adverse events
(TEAEs) were mild in severity, transient and self-resolving (with
one moderate case of nausea that resolved with food intake). There
were no severe adverse events (AEs). AEs observed in >1 patient
and deemed to be related to study drug were insomnia,4
pollakiuria, salivary hypersecretion, decreased appetite, dizziness
and nausea.
- There were no serious AEs (SAEs) reported or TEAEs leading to
study drug discontinuation in patients with NT1. There were no
drug-related, treatment-emergent, clinically meaningful changes
from baseline in laboratory values at any dose. Additionally, no
cardiovascular safety signals were identified in vital signs or
electrocardiogram (ECG) parameters.
"We're encouraged by the results of this proof-of-concept study
of ALKS 2680 in patients with narcolepsy type 1. The clear dose
response reinforced our design principles for this program, and we
are looking forward to further characterizing the efficacy and
safety of ALKS 2680 in patients with narcolepsy type 1 in the
ongoing Vibrance-1 phase 2 study," said Craig Hopkinson, M.D., Chief Medical Officer and
Executive Vice President, Research & Development at
Alkermes.
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, crossover
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 (PK) 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 crossover period, along with plasma PK, and
patient-reported measures of alertness on the Karolinska Sleepiness
Scale (KSS).
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.5 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 previously evaluated in a
phase 1 study in healthy volunteers and people living with
narcolepsy type 1, narcolepsy type 2 and idiopathic hypersomnia and
is currently being evaluated in the Vibrance-1 phase 2 study in
patients with narcolepsy type 1.
About the Vibrance-1 Study
Vibrance-1 is a phase 2,
randomized, double-blind, dose-range-finding study evaluating the
safety and efficacy of ALKS 2680 compared to placebo in patients
with narcolepsy type 1. More information can be found at
www.clinicaltrials.gov (identifier: NCT06358950) and
www.vibrancestudies.com (for U.S. audiences only).
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, including narcolepsy.
Headquartered in Ireland, Alkermes
also has a corporate office and research and development center in
Massachusetts and a manufacturing
facility in 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 clinical development
activities for, and the potential therapeutic and commercial value
of, ALKS 2680 for the treatment of narcolepsy. 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
future clinical studies or real-world results; 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 Nine of 10 participants completed all 4-way
randomized crossover periods. One participant withdrew from the
study after receiving the initial ALKS 2680 dose due to poor venous
access and inability to undergo further blood draws.
2 Patients with NT1 in the phase 1b study had baseline sleep latencies ranging
from one to 15 minutes.
3 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.
4 Insomnia includes TEAE terms of insomnia and
middle insomnia (i.e., difficulty maintaining sleep).
5 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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