— Novel Regimen Enables Physicians to Fully Dose Up to
Two Months of ARISTADA Treatment on Day One —
DUBLIN, July 2, 2018 /PRNewswire/ -- Alkermes
plc (Nasdaq: ALKS) today announced that the U.S. Food and Drug
Administration (FDA) has approved ARISTADA INITIO™
(aripiprazole lauroxil) for the initiation of ARISTADA®
(aripiprazole lauroxil), a long-acting injectable atypical
antipsychotic for the treatment of schizophrenia in adults. For the
first time, ARISTADA INITIO, in combination with a single 30 mg
dose of oral aripiprazole, provides physicians with an alternative
regimen to initiate patients onto any dose of ARISTADA on day one.
ARISTADA INITIO is expected to be available in mid-July.
For people living with schizophrenia, medication compliance and
continuity of care can be challenging and the transition from
inpatient care to outpatient settings can be an especially
vulnerable time.1 Previously, the standard initiation
regimen for ARISTADA included 21 consecutive days of oral
aripiprazole starting with the first ARISTADA dose. The ARISTADA
INITIO regimen provides patients with relevant levels of
aripiprazole within four days of initiation. The result is an
alternative initiation regimen that gives healthcare providers an
additional tool to support patients during this critical time in
their treatment journey.
"The approval of ARISTADA INITIO makes ARISTADA the first and
only long-acting atypical antipsychotic that can be initiated on
day one, representing an important addition to the treatment
paradigm for the complex illness of schizophrenia," said
David Walling, Ph.D., Chief
Executive Officer and Principal Investigator of the Collaborative
Neuroscience Network. "For physicians and caregivers alike, the
ARISTADA INITIO regimen provides a level of confidence that
patients can walk out the door with up to two months of coverage
with a proven medication in their system. This supports continuity
of care for patients and allows the care team to focus their
efforts on other aspects of the treatment paradigm that contribute
to long-term positive outcomes."
ARISTADA and ARISTADA INITIO both contain aripiprazole lauroxil;
however, the two medications are not interchangeable because of
differing pharmacokinetic profiles. ARISTADA INITIO leverages the
company's proprietary NanoCrystal® technology and is
designed to provide an extended-release formulation using a smaller
particle size of aripiprazole lauroxil compared to ARISTADA,
thereby enabling faster dissolution and leading to more rapid
achievement of relevant levels of aripiprazole.
ARISTADA INITIO can be used for initiation onto any dose of
ARISTADA (441 mg, 662 mg or 882 mg monthly, 882 mg once every
six weeks and 1064 mg once every two months), offering a wide range
of flexible dosing options for patients and healthcare providers.
The first ARISTADA dose may be administered on the same day as
ARISTADA INITIO or up to 10 days thereafter.
"Long-acting injectable atypical antipsychotics have an
increasingly recognized role in the treatment of schizophrenia. The
ability to initiate ARISTADA on day one may be particularly useful
in the hospital setting, where more than one-third of patients
initiate onto long-acting therapies," said Craig Hopkinson, M.D., Chief Medical Officer and
Senior Vice President of Medicines Development and Medical Affairs
at Alkermes. "The approval of ARISTADA INITIO adds an important new
option to our growing schizophrenia portfolio and reaffirms
Alkermes' commitment to developing innovative treatments that
address the real-world needs of people living with
schizophrenia."
About Schizophrenia
Schizophrenia is a chronic, severe and disabling brain disorder.
The disease is marked by positive symptoms (hallucinations and
delusions) and negative symptoms (depression, blunted emotions and
social withdrawal), as well as by disorganized thinking. An
estimated 2.4 million American adults live with
schizophrenia,2 with men and women affected equally.
About ARISTADA INITIO™
ARISTADA INITIO, in
combination with a single 30 mg dose of oral aripiprazole, can be
used to initiate onto any dose of ARISTADA. The first ARISTADA dose
may be administered on the same day as ARISTADA INITIO or up to 10
days thereafter.
About ARISTADA®
ARISTADA is an injectable
atypical antipsychotic approved in four doses and three dosing
durations for the treatment of schizophrenia (441 mg, 662 mg or 882
mg monthly, 882 mg once every six weeks and 1064 mg once every two
months). Once in the body, ARISTADA converts to aripiprazole.
INDICATION and IMPORTANT SAFETY INFORMATION for
ARISTADA INITIO™ (aripiprazole lauroxil) and
ARISTADA® (aripiprazole lauroxil) extended-release
injectable suspension, for intramuscular use
INDICATION
ARISTADA INITIO, in combination with oral aripiprazole, is
indicated for the initiation of ARISTADA when used for the
treatment of schizophrenia in adults.
ARISTADA is indicated for the treatment of schizophrenia.
IMPORTANT SAFETY INFORMATION
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WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH
DEMENTIA-RELATED PSYCHOSIS
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Elderly patients
with dementia-related psychosis treated with antipsychotic drugs
are at an increased risk of death. ARISTADA INITIO and ARISTADA are
not approved for the treatment of patients with dementia-related
psychosis.
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Contraindication: Known hypersensitivity reaction to
aripiprazole. Reactions have ranged from pruritus/urticaria to
anaphylaxis.
Cerebrovascular Adverse Reactions, Including Stroke:
Increased incidence of cerebrovascular adverse reactions (e.g.,
stroke, transient ischemic attack), including fatalities, have been
reported in placebo-controlled trials of elderly patients with
dementia-related psychosis treated with risperidone, aripiprazole,
and olanzapine. ARISTADA INITIO and ARISTADA are not approved for
the treatment of patients with dementia-related psychosis.
Potential for Dosing and Medication Errors: Medication
errors, including substitution and dispensing errors, between
ARISTADA INITIO and ARISTADA could occur. ARISTADA INITIO is
intended for single administration only. Do not substitute ARISTADA
INITIO for ARISTADA because of differing pharmacokinetic
profiles.
Neuroleptic Malignant Syndrome (NMS): A potentially fatal
symptom complex may occur with administration of antipsychotic
drugs, including ARISTADA INITIO and ARISTADA. Clinical
manifestations of NMS include hyperpyrexia, muscle rigidity,
altered mental status, and evidence of autonomic instability
(irregular pulse or blood pressure, tachycardia, diaphoresis, and
cardiac dysrhythmia). Additional signs may include elevated
creatine phosphokinase, myoglobinuria (rhabdomyolysis), and acute
renal failure. The management of NMS should include:
1) immediate discontinuation of antipsychotic drugs and other
drugs not essential to concurrent therapy; 2) intensive
symptomatic treatment and medical monitoring; and 3) treatment
of any concomitant serious medical problems for which specific
treatments are available.
Tardive Dyskinesia (TD): The risk of developing TD (a
syndrome of abnormal, involuntary movements) and the potential for
it to become irreversible are believed to increase as the duration
of treatment and the total cumulative dose of antipsychotic
increase. The syndrome can develop, although much less commonly,
after relatively brief treatment periods at low doses. Prescribing
antipsychotics should be consistent with the need to minimize TD.
Discontinue ARISTADA if clinically appropriate. TD may remit,
partially or completely, if antipsychotic treatment is
withdrawn.
Metabolic Changes: Atypical antipsychotic drugs have been
associated with metabolic changes that include:
- Hyperglycemia/Diabetes Mellitus: Hyperglycemia, in some
cases extreme and associated with ketoacidosis, coma, or death, has
been reported in patients treated with atypical antipsychotics.
There have been reports of hyperglycemia in patients treated with
oral aripiprazole. Patients with diabetes should be regularly
monitored for worsening of glucose control; those with risk factors
for diabetes should undergo baseline and periodic fasting blood
glucose testing. Any patient treated with atypical antipsychotics
should be monitored for symptoms of hyperglycemia, including
polydipsia, polyuria, polyphagia, and weakness. Patients who
develop symptoms of hyperglycemia should also undergo fasting blood
glucose testing. In some cases, hyperglycemia has resolved when the
atypical antipsychotic was discontinued; however, some patients
require continuation of antidiabetic treatment despite
discontinuation of the suspect drug.
- Dyslipidemia: Undesirable alterations in lipids have
been observed in patients treated with atypical antipsychotics.
- Weight Gain: Weight gain has been observed with atypical
antipsychotic use. Clinical monitoring of weight is
recommended.
Pathological Gambling and Other Compulsive
Behaviors: Compulsive or uncontrollable urges to gamble
have been reported with use of aripiprazole. Other compulsive urges
less frequently reported include sexual urges, shopping, binge
eating and other impulsive or compulsive behaviors which may result
in harm for the patient and others if not recognized. Closely
monitor patients and consider dose reduction or stopping
aripiprazole if a patient develops such urges.
Orthostatic Hypotension: Aripiprazole may cause
orthostatic hypotension which can be associated with dizziness,
lightheadedness, and tachycardia. Monitor heart rate and blood
pressure, and warn patients with known cardiovascular or
cerebrovascular disease and risk of dehydration and syncope.
Falls: Antipsychotics including ARISTADA INITIO and
ARISTADA may cause somnolence, postural hypotension or motor and
sensory instability which may lead to falls and subsequent
injury. Upon initiating treatment and recurrently, complete
fall risk assessments as appropriate.
Leukopenia, Neutropenia, and Agranulocytosis: Leukopenia,
neutropenia and agranulocytosis have been reported with
antipsychotics. Monitor complete blood count in patients with
pre-existing low white blood cell count (WBC)/absolute neutrophil
count or history of drug-induced leukopenia/neutropenia.
Discontinue ARISTADA INITIO and/or ARISTADA at the first sign of a
clinically significant decline in WBC and in severely neutropenic
patients.
Seizures: Use with caution in patients with a history of
seizures or with conditions that lower the seizure threshold.
Potential for Cognitive and Motor Impairment: ARISTADA
INITIO and ARISTADA may impair judgment, thinking, or motor skills.
Patients should be cautioned about operating hazardous machinery,
including automobiles, until they are certain therapy with ARISTADA
INITIO and/or ARISTADA does not affect them adversely.
Body Temperature Regulation: Disruption of the body's
ability to reduce core body temperature has been attributed to
antipsychotic agents. Advise patients regarding appropriate care in
avoiding overheating and dehydration. Appropriate care is advised
for patients who may exercise strenuously, may be exposed to
extreme heat, receive concomitant medication with anticholinergic
activity, or are subject to dehydration.
Dysphagia: Esophageal dysmotility and aspiration have
been associated with antipsychotic drug use; use caution in
patients at risk for aspiration pneumonia.
Concomitant Medication: ARISTADA INITIO is only available
at a single strength as a single-dose pre-filled syringe, so dosage
adjustments are not possible. Avoid use in patients who are known
CYP2D6 poor metabolizers or taking strong CYP3A4 inhibitors, strong
CYP2D6 inhibitors, or strong CYP3A4 inducers, antihypertensive
drugs or benzodiazepines.
Depending on the ARISTADA dose, adjustments may be recommended
if patients are 1) known as CYP2D6 poor metabolizers and/or 2)
taking CYP3A4 inhibitors, CYP2D6 inhibitors, or CYP3A4 inducers for
greater than 2 weeks. Avoid use of ARISTADA 662 mg, 882
mg, or 1064 mg for patients taking both strong CYP3A4 inhibitors
and strong CYP2D6 Inhibitors. (See Table 4 in the ARISTADA full
Prescribing Information)
Commonly Observed Adverse Reactions: In pharmacokinetic
studies the safety profile of ARISTADA INITIO was generally
consistent with that observed for ARISTADA. The most common
adverse reaction (≥5% incidence and at least twice the rate of
placebo reported by patients treated with ARISTADA 441 mg and 882
mg monthly) was akathisia.
Injection-Site Reactions: In pharmacokinetic studies
evaluating ARISTADA INITIO, the incidences of injection site
reactions with ARISTADA INITIO were similar to the incidence
observed with ARISTADA. Injection-site reactions were
reported by 4%, 5%, and 2% of patients treated with 441 mg ARISTADA
(monthly), 882 mg ARISTADA (monthly), and placebo, respectively.
Most of these were injection-site pain and associated with the
first injection and decreased with each subsequent injection. Other
injection-site reactions (induration, swelling, and redness)
occurred at less than 1%.
Dystonia: Symptoms of dystonia, prolonged abnormal
contractions of muscle groups, may occur in susceptible individuals
during the first days of treatment and at low doses.
Pregnancy/Nursing: May cause extrapyramidal and/or
withdrawal symptoms in neonates with third trimester exposure.
Advise patients to notify their healthcare provider of a known or
suspected pregnancy. Inform patients that there is a pregnancy
exposure registry that monitors pregnancy outcomes in women exposed
to ARISTADA INITIO and/or ARISTADA during pregnancy. Aripiprazole
is present in human breast milk. The benefits of breastfeeding
should be considered along with the mother's clinical need for
ARISTADA INITIO and/or ARISTADA and any potential adverse effects
on the infant from ARISTADA INITIO and/or ARISTADA or from the
underlying maternal condition.
Please see full Prescribing Information, including Boxed Warning
for ARISTADA INITIO and ARISTADA.
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About Alkermes plc
Alkermes plc is a fully
integrated, global biopharmaceutical company developing innovative
medicines for the treatment of central nervous system (CNS)
diseases. The company has a diversified commercial product
portfolio and a substantial clinical pipeline of product candidates
for chronic diseases that include schizophrenia, depression,
addiction and multiple sclerosis. Headquartered in Dublin, Ireland, Alkermes plc has an 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 timing of the
commercial launch of ARISTADA INITIO in the U.S., the
commercialization of ARISTADA INITIO and the potential therapeutic
and commercial value of ARISTADA INITIO for initiation of ARISTADA
for the treatment of schizophrenia. 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: when ARISTADA INITIO will
become commercially available; whether the pharmacokinetic and
safety results demonstrated in the company's open-label
pharmacokinetic, safety and tolerability study of ARISTADA INITIO
for initiation of ARISTADA for the treatment of schizophrenia will
be predictive of results when commercialized; whether ARISTADA
INITIO will be commercialized successfully; whether third-party
payers will cover or reimburse ARISTADA INITIO for initiation of
ARISTADA for the treatment of schizophrenia; 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, 2017 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.
ARISTADA INITIO™ is a trademark of, and
ARISTADA® and NanoCrystal® are registered
trademarks of, Alkermes Pharma Ireland Limited.
1 Markowitz, M., et al. (2013). "Antipsychotic
adherence patterns and health care utilization and costs among
patients discharged after a schizophrenia-related
hospitalization." BMC Psychiatry 13(1): 246.
2 National Institutes of Health. Schizophrenia.
Accessed on June 30, 2018 from
https://report.nih.gov/nihfactsheets/ViewFactSheet.aspx?csid=67.
Alkermes
Contacts:
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For
Investors:
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Eva Stroynowski
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+1-781-609-6823
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Sandy
Coombs
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+1-781-609-6377
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For Media:
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Marisa Borgasano
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+1-781-609-6659
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