— Results Demonstrated that LYBALVI was
Generally Well Tolerated With Stability of Body Weight and
Metabolic Profile, and Durable Symptom Control, for Up to Four
Years of Treatment —
DUBLIN, Jan. 3, 2024 /PRNewswire/ -- Alkermes
plc (Nasdaq: ALKS) today announced topline results 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 with
schizophrenia, schizophreniform disorder or bipolar I disorder for
up to four years of treatment, following treatment received in
prior LYBALVI studies. 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.
In this global, open-label extension study, 523 participants
received at least one dose of LYBALVI and 35.9% of participants
completed the four-year treatment period. The safety profile of
LYBALVI was consistent with previous studies. Patients' symptoms of
schizophrenia or bipolar I disorder remained stable with up to four
years of treatment with LYBALVI, as measured by the Clinical Global
Impression of Severity (CGI-S) scale (mean change from baseline in
CGI-S score of -0.28). Long-term treatment with LYBALVI was
associated with minimal changes in body weight (mean change from
baseline of +1.47 kg) and waist circumference (observed mean change
from baseline of +0.61 cm) with up to four years of treatment.
Similarly, there were generally minimal changes in lipid and
glycemic parameters, including HDL cholesterol, LDL cholesterol,
triglycerides, fasting glucose and HbA1c over the measured time
period. Overall, 60% of patients reported an adverse event (AE).
The most common AEs reported (>5%) were weight gain, headache,
anxiety, insomnia, somnolence, nausea and weight decrease; most AEs
were mild to moderate in severity.
"As clinicians, we see firsthand the challenges that people
living with complex mental health conditions may face in finding
treatment options that work for them long term, in terms of both
efficacy and tolerability," said Jacob S.
Ballon, M.D., M.P.H., Clinical Professor of Psychiatry and
Behavioral Sciences at Stanford
University and a study investigator. "These data, which
demonstrated long-term tolerability and symptom control, as well as
stability across key weight and metabolic factors, underscore
LYBALVI's established safety and efficacy profile and provide
important information for clinicians as we navigate treatment
decisions with our patients in the real world."
"We are pleased to share the topline results from this
long-term, open-label study. These data highlight the potential
utility of LYBALVI as a foundational maintenance treatment option
for people living with schizophrenia or bipolar I disorder and
reinforce the safety profile of LYBALVI established in previous
studies," said Craig Hopkinson,
M.D., Executive Vice President, Research & Development and
Chief Medical Officer at Alkermes. "In this study, patients
taking LYBALVI experienced sustained treatment effect and
tolerability, including stability across multiple
metabolic parameters. Against the backdrop of average treatment
persistency of less than six months for oral atypical
antipsychotics generally, we are encouraged that more than
one-third of subjects completed four years of treatment with
LYBALVI."
Alkermes expects to submit results from this open-label,
long-term study to a peer-reviewed journal for publication and to
present additional study results at upcoming scientific
meetings.
Phase 3, Open-Label Study Design
This was a
multicenter, phase 3, open-label extension study assessing 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 ENLIGHTEN-1 safety
extension study; the ENLIGHTEN-2 safety extension study (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, patients continued their daily dose
of LYBALVI (olanzapine 5-20 mg + samidorphan 10 mg) from their
antecedent study for up to an additional four years, with dose
adjustments determined by the investigator. A total of 524 patients
enrolled in the study, and 523 received ≥1 dose of LYBALVI.
Baseline was established based on these 523 patients and changes as
compared to baseline were based on those patients who completed
four years of open-label treatment with LYBALVI. Patients were
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
(AEs). Changes in lipid (high-density lipoprotein [HDL],
low-density lipoprotein [LDL], and total cholesterol and
triglycerides) and glycemic (glucose and glycosylated hemoglobin
[HbA1c]) parameters were evaluated. Antipsychotic
efficacy was assessed using the Clinical Global
Impressions–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.
IMPORTANT SAFETY INFORMATION for LYBALVI®
(olanzapine and samidorphan)
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 above.
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 creatinine 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, 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.
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): asthenia, dry mouth, constipation, increased
appetite, somnolence, dizziness, tremor
- Bipolar I Disorder, Manic or Mixed Episodes, adjunct to
Lithium or Valproate (olanzapine): dry mouth,
dyspepsia, 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 see 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, 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.
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:
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Marisa Borgasano,
+1 781 609 6659
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