DUBLIN, April 8, 2024 /PRNewswire/ -- Alkermes plc
(Nasdaq: ALKS) today announced the oral presentation of clinical
data at the 2024 Congress of the Schizophrenia International
Research Society (SIRS), which took place April 3-7, 2024 in Florence, Italy. Analyses were presented from
a phase 3, open-label extension study assessing the long-term
safety, tolerability and durability of treatment effect of
LYBALVI® (olanzapine and samidorphan) in patients who
received up to four years of treatment. LYBALVI is approved in
the U.S. for the treatment of adults with schizophrenia,
and for the treatment of adults with bipolar I disorder, as a
maintenance monotherapy or for the acute treatment of manic or
mixed episodes, as monotherapy or as adjunct to lithium or
valproate.
René Kahn, M.D., Ph.D., Icahn School of Medicine at Mount Sinai,
presented the data in an oral presentation during the "New
Pharmacological Treatments and Assessments" session. New analyses
were presented related to the subset of participants in the study
who reached at least two years of treatment and the subset of
participants who reached four years of treatment, providing
information as to the long-term safety profile and durability
of treatment effect of LYBALVI at specific points in time. Key
findings are as follows:
- Patient Disposition: 523 participants received at least
one dose of LYBALVI in this global, open-label extension study.
Depending on geography and enrollment date, patients had the
opportunity to receive up to two to four years of treatment in this
study. 188 (35.9%) participants completed the study, as defined in
the protocol, having received between two to four years of
treatment and attended their final study visit. There were 451
patients who had the opportunity to receive at least two years of
LYBALVI treatment, of which 242 (53.7%) did so. There were 335
patients who had the opportunity to receive four years of LYBALVI
treatment, of which 109 (32.5%) did so.
- Changes in Weight, Waist Circumference, and Metabolic
Parameters: For patients who contributed data to the two-year
assessment, mean change from baseline in body weight was 0.84 kg
and waist circumference was -0.56 cm. For patients who contributed
data to the four-year assessment, the mean change from baseline in
body weight was 2.65 kg and waist circumference was 1.37 cm. In
addition, there were minimal changes in lipid and glycemic
parameters over the treatment period.
- Adverse Events: The adverse event (AE) profile of
LYBALVI was consistent with previous studies. Overall, 60% of
participants reported at least one AE. The most common AEs reported
(>5%) were weight increase, headache, anxiety, insomnia,
somnolence, nausea and weight decrease. Most AEs were mild to
moderate in severity.
- Symptoms: Patients' symptoms of schizophrenia or bipolar
I disorder remained stable, as measured by the Clinical Global
Impression of Severity (CGI-S) scale. For patients who contributed
data to the two-year assessment, mean change from baseline in CGI-S
score was -0.18. For patients who contributed data to the four-year
assessment, mean change from baseline in CGI-S was -0.24.
According to Dr. Kahn, "The study results, which include data
from patients who received up to four years of treatment on
LYBALVI, demonstrated that the combination of olanzapine and
samidorphan delivered long-term tolerability, including across key
weight and metabolic parameters, and sustained symptom control,
further reinforcing LYBALVI's potential utility as a foundational
maintenance treatment option for people living with schizophrenia
or bipolar I disorder."
About the Phase 3, Open-Label Extension Study
Design
This was an international, multicenter, phase 3,
open-label extension study that assessed the long-term safety,
tolerability and durability of treatment effect of LYBALVI for up
to four years. Patients were eligible to enroll within seven days
of completing one of three antecedent phase 3 clinical trials
investigating LYBALVI: the 52-week ENLIGHTEN-1 and ENLIGHTEN-2
safety extension studies (rollover extensions of the ENLIGHTEN-1
and ENLIGHTEN-2 phase 3 pivotal randomized controlled trials in
adults with schizophrenia); and the 12-week ENLIGHTEN-Early
randomized controlled trial comparing LYBALVI to olanzapine in
young adults with recent-onset schizophrenia, schizophreniform
disorder, or bipolar I disorder. In this long-term extension study,
the daily dose of LYBALVI (olanzapine 5-20 mg + samidorphan 10 mg)
was selected to maintain consistency with patients' therapeutic
dose of either LYBALVI or olanzapine received in their antecedent
study, with dose adjustments determined by the investigator.
Depending on geography and the time of enrollment into the
long-term extension study, patients had the opportunity to receive
at least two and up to four years of additional LYBALVI therapy. A
total of 524 patients enrolled in the study, and 523 received ≥1
dose of LYBALVI. At baseline, the overall population was mostly
male (61.6%) and White (72.7%), with a mean age of 35.1 years.
Safety assessments included changes from baseline in body weight
and waist circumference and the incidence of adverse events.
Changes in lipid (high-density lipoprotein [HDL], low-density
lipoprotein [LDL], and total cholesterol and triglycerides) and
glycemic (glucose) parameters were evaluated in a fasting state.
Changes in glycemic (glycosylated hemoglobin [HbA1c])
parameters also were evaluated. Durability of treatment was
assessed using the Clinical Global Impression of Severity (CGI-S)
scale.
About Schizophrenia and Schizophreniform Disorder
Schizophrenia is a serious brain disorder marked by positive
symptoms (hallucinations and delusions, disorganized speech and
thoughts, and agitated or repeated movements) and negative symptoms
(depression, blunted emotions and social
withdrawal).1 Schizophrenia affects approximately
1.1% of the U.S. population.2 Schizophreniform disorder
exhibits symptoms similar to schizophrenia, but without sufficient
duration for a diagnosis of schizophrenia (one to six
months).1
About Bipolar I Disorder
Bipolar disorder is a brain disorder that is marked by extreme
changes in a person's mood, energy and ability to function.
Individuals with this brain disorder may experience debilitating
mood states, including extreme highs (mania) and extreme lows
(depression). Bipolar I disorder is characterized by the
occurrence of at least one manic episode, with or without the
occurrence of a major depressive episode, and affects approximately
1% of the adult population in the United States in any
given year.3
About LYBALVI® (olanzapine and
samidorphan)
LYBALVI® (olanzapine and
samidorphan) is a once-daily, oral atypical antipsychotic drug
approved in the U.S. for the treatment of adults with schizophrenia
and for the treatment of adults with bipolar I disorder, as a
maintenance monotherapy or for the acute treatment of manic or
mixed episodes, as monotherapy or an adjunct to lithium or
valproate. LYBALVI is a combination of olanzapine, an atypical
antipsychotic, and samidorphan, an opioid antagonist, in a single
bilayer tablet. LYBALVI is available in fixed dosage
strengths composed of 10 mg of samidorphan and 5 mg, 10 mg, 15 mg
or 20 mg of olanzapine.
INDICATIONS AND IMPORTANT SAFETY INFORMATION for
LYBALVI® (olanzapine and samidorphan)
INDICATIONS
LYBALVI is indicated for the treatment
of:
- Schizophrenia in adults
- Bipolar I disorder in adults
- Acute treatment of manic or mixed episodes as monotherapy and
as adjunct to lithium or valproate
- Maintenance monotherapy treatment
IMPORTANT SAFETY INFORMATION
Boxed Warning: Elderly patients with dementia-related
psychosis treated with antipsychotic drugs are at an increased risk
of death. LYBALVI is not approved for the treatment of patients
with dementia-related psychosis.
Contraindications: LYBALVI is contraindicated in
patients who are using opioids or are undergoing acute opioid
withdrawal. If LYBALVI is administered with lithium or valproate,
refer to the lithium or valproate Prescribing Information for the
contraindications for these products.
Cerebrovascular Adverse Reactions in Elderly Patients with
Dementia-Related Psychosis, including stroke, transient
ischemia attack, and fatalities. See Boxed Warning.
Precipitation of Severe Opioid Withdrawal in Patients who are
Physiologically Dependent on Opioids: LYBALVI can
precipitate opioid withdrawal in patients who are dependent on
opioids, which can lead to an opioid withdrawal syndrome, sometimes
requiring hospitalization. LYBALVI is contraindicated in patients
who are using opioids or undergoing acute opioid withdrawal. Prior
to initiating LYBALVI, there should be at least a 7‑day opioid-free
interval from last use of short-acting opioids, and at least a
14-day opioid-free interval from the last use of long-acting
opioids. Explain the risks associated with precipitated withdrawal
and the importance of giving an accurate account of last opioid use
to patients and caregivers.
Vulnerability to Life-Threatening Opioid Overdose:
Attempting to overcome opioid blockade with high or repeated doses
of exogenous opioids could lead to life-threatening or fatal opioid
intoxication, particularly if LYBALVI therapy is interrupted or
discontinued, subjecting the patient to high levels of unopposed
opioid agonist as the samidorphan blockade wanes. Inform patients
of the potential consequences of trying to overcome the opioid
blockade and the serious risks of taking opioids concurrently with
LYBALVI or while transitioning off LYBALVI. In emergency
situations, if a LYBALVI-treated patient requires opioid treatment
as part of anesthesia or analgesia, discontinue LYBALVI. Opioids
should be administered by properly trained individual(s) and
patient should be continuously monitored in a setting equipped and
staffed for cardiopulmonary resuscitation. Patients with a history
of chronic opioid use prior to treatment with LYBALVI may have
decreased opioid tolerance if LYBALVI therapy is interrupted or
discontinued. Advise patients that this decreased tolerance may
increase the risk of opioid overdose if opioids are resumed at the
previously tolerated dosage.
Neuroleptic Malignant Syndrome, a potentially fatal
reaction. Signs and symptoms include hyperpyrexia, muscle rigidity,
delirium, autonomic instability, elevated
creatine phosphokinase, myoglobinuria (and/or rhabdomyolysis),
and acute renal failure. Manage with immediate discontinuation,
intensive symptomatic treatment, and close monitoring.
Drug Reaction with Eosinophilia and Systemic Symptoms
(DRESS), a potentially fatal condition reported with exposure
to olanzapine, a component of LYBALVI. Symptoms include a cutaneous
reaction (such as rash or exfoliative dermatitis), eosinophilia,
fever, and/or lymphadenopathy with systemic complications such as
hepatitis, nephritis, pneumonitis, myocarditis, and/or
pericarditis. Discontinue if DRESS is suspected.
Metabolic Changes, including hyperglycemia, diabetes
mellitus, dyslipidemia, and weight gain. Hyperglycemia, in some
cases extreme and associated with ketoacidosis or hyperosmolar coma
or death, has been reported in patients treated with atypical
antipsychotics. Any patient treated with LYBALVI should be
monitored for symptoms of hyperglycemia including polydipsia,
polyuria, polyphagia, and weakness. In some cases,
hyperglycemia has resolved when the atypical antipsychotic was
discontinued; however, some patients required anti-diabetic
treatment despite discontinuation of the suspect drug. Measure
weight and assess fasting glucose and lipids when
initiating LYBALVI and monitor periodically.
Tardive Dyskinesia (TD): Risk of developing TD (a
syndrome of potentially irreversible, involuntary, dyskinetic
movements) and the likelihood it will become irreversible increases
with the duration of treatment and the cumulative dose. The
syndrome can develop after a relatively brief treatment period,
even at low doses, or after discontinuation. Given these
considerations, LYBALVI should be prescribed in a manner that is
most likely to reduce the risk of tardive dyskinesia. If signs and
symptoms of TD appear, drug discontinuation should be
considered.
Orthostatic Hypotension and Syncope: Monitor orthostatic
vital signs in patients who are vulnerable to hypotension, patients
with known cardiovascular disease, and patients with
cerebrovascular disease.
Falls: LYBALVI may cause somnolence, postural
hypotension, and motor and sensory instability, which may lead to
falls, and consequently, fractures or other injuries. Assess
patients for risk when using LYBALVI.
Leukopenia, Neutropenia, and Agranulocytosis (including fatal
cases): Perform complete blood counts in patients with a
history of a clinically significant low white blood cell (WBC)
count or history of leukopenia or neutropenia. Discontinue LYBALVI
if clinically significant decline in WBC occurs in the absence of
other causative factors.
Dysphagia: Use LYBALVI with caution in patients at risk
for aspiration.
Seizures: Use LYBALVI with caution in patients with a
history of seizures or with conditions that lower the seizure
threshold.
Potential for Cognitive and Motor Impairment: Because
LYBALVI may cause somnolence, and may impair judgment, thinking, or
motor skills, caution patients about operating hazardous machinery,
including motor vehicles, until they are certain that LYBALVI does
not affect them adversely.
Body Temperature Dysregulation: Use LYBALVI with caution
in patients who may experience conditions that increase core body
temperature (e.g., strenuous exercise, extreme heat, dehydration,
or concomitant use with anticholinergics).
Anticholinergic (Antimuscarinic) Effects: Olanzapine, a
component of LYBALVI, was associated with constipation, dry mouth,
and tachycardia. Use LYBALVI with caution with other
anticholinergic medications and in patients with urinary retention,
prostatic hypertrophy, constipation, paralytic ileus or related
conditions. In postmarketing experience, the risk for severe
adverse reactions (including fatalities) was increased with
concomitant use of anticholinergic medications.
Hyperprolactinemia: LYBALVI elevates prolactin levels.
Galactorrhea, amenorrhea, gynecomastia, and impotence have been
reported in patients receiving prolactin-elevating compounds.
Risks Associated with Combination Treatment with Lithium or
Valproate: If LYBALVI is administered with lithium or
valproate, refer to the lithium or valproate Prescribing
Information for a description of the risks for these
products.
Interference with Laboratory Tests for Opioid Detection:
LYBALVI may cause false positive results with urinary immunoassay
methods for detecting opioids. Use an alternative analytical
technique (e.g., chromatographic methods) to confirm positive
opioid urine drug screen results.
Most Common Adverse Reactions observed in clinical trials
were:
- Schizophrenia (LYBALVI): weight increased, somnolence,
dry mouth, and headache
- Bipolar I Disorder, Manic or Mixed Episodes
(olanzapine): somnolence, dry mouth, dizziness, asthenia,
constipation, dyspepsia, increased appetite, and tremor
- Bipolar I Disorder, Manic or Mixed Episodes, adjunct to
lithium or valproate (olanzapine): dry mouth, weight gain,
increased appetite, dizziness, back pain, constipation, speech
disorder, increased salivation, amnesia, paresthesia
Concomitant Medication: LYBALVI is contraindicated in
patients who are using opioids or undergoing acute opioid
withdrawal. Concomitant use of LYBALVI is not recommended with
strong CYP3A4 inducers, levodopa and dopamine agonists. Reduce
dosage of LYBALVI when using with strong CYP1A2 inhibitors.
Increase dosage of LYBALVI with CYP1A2 inducers. Use caution with
diazepam, alcohol, other CNS acting drugs, or in patients receiving
anticholinergic (antimuscarinic) medications. Monitor blood
pressure and reduce dosage of antihypertensive drug in accordance
with its approved product labeling.
Pregnancy: May cause extrapyramidal and/or
withdrawal symptoms in neonates with third trimester exposure.
Advise patients to notify their healthcare provider if they become
pregnant or intend to become pregnant during treatment with
LYBALVI. Inform patients that there is a pregnancy exposure
registry that monitors pregnancy outcomes in women exposed to
LYBALVI during pregnancy.
Renal Impairment: LYBALVI is not recommended for
patients with end-stage renal disease (eGFR of
<15 mL/minute/1.73 m2).
To report SUSPECTED ADVERSE REACTIONS, contact Alkermes at
1-888-235-8008 or FDA at 1-800-FDA-1088 or
www.fda.gov/medwatch.
Please click here for full Prescribing
Information, including Boxed Warning, for LYBALVI.
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 LYBALVI for people living with
schizophrenia or bipolar I disorder. 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 clinical results for
LYBALVI will be predictive of future clinical results or real-world
results; whether LYBALVI could be shown to be ineffective or
unsafe; 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.
LYBALVI ® is a registered trademark
of Alkermes Pharma Ireland Limited, used by Alkermes, Inc. under
license.
References
1 American Psychiatric
Association. Schizophrenia Spectrum and Other Psychiatric
Disorders. Diagnostic and Statistical Manual of Mental
Disorders. 5th ed. Washington,
DC: American Psychiatric Publishing; 2013.
2 Cloutier M. Journal of Clinical Psychiatry. 2016
Jun; 77(6): 764-71.
https://www.psychiatrist.com/jcp/schizophrenia/economic-burden-schizophrenia-united-states-2013/
3 Merikangas et al. Lifetime and 12-Month
Prevalence of Bipolar Spectrum Disorder in the National Comorbidity
Survey Replication. Arch Gen Psychiatry, 2007 May;
64(5): 543-552.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1931566/
Alkermes
Contacts:
|
For
Investors:
|
Sandy Coombs, +1
781 609 6377
|
For
Media:
|
Marisa Borgasano,
+1 781 609 6659
|
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