– Supplemental New Drug Application for ARISTADA Two-Month Dose Under
Review by FDA With Action Expected by June 5, 2017 –
DUBLIN--(BUSINESS WIRE)--Mar. 20, 2017--
plc (NASDAQ: ALKS) today announced that data for the two-month
dosing option of ARISTADA® (aripiprazole lauroxil)
extended-release injectable suspension for the treatment of
schizophrenia will be presented at the 16th International
Congress on Schizophrenia Research (ICOSR) in San Diego, March 24-28,
2017. This will be the company’s first presentation of pharmacokinetic
(PK) data on the investigational two-month dosing option of ARISTADA at
a medical meeting. A supplemental New Drug Application (sNDA) for the
two-month dosing option of ARISTADA is currently under review with the
U.S. Food and Drug Administration (FDA) and has been assigned a
Prescription Drug User Fee Act (PDUFA) action date of June 5, 2017. This
potential new two-month offering would expand the range of ARISTADA
dosing intervals to include a third option for patients with
schizophrenia. ARISTADA was approved by the FDA in October 2015 as the
first long-acting atypical antipsychotic with once-monthly and
once-every-six-weeks dosing options.
“Schizophrenia is a complex condition in which symptoms and severity of
the disease varies, and healthcare providers need a variety of options
to help individualize treatment based on patient needs,” said Elliot
Ehrich, M.D., Chief Medical Officer of Alkermes. “We are designing
ARISTADA to offer unprecedented flexibility in terms of doses and dosing
intervals, and we believe a two-month offering of ARISTADA could be an
important new treatment option for the treatment of schizophrenia.”
A poster, titled “Pharmacokinetic Analysis of a 2-Month Regimen of
Aripiprazole Lauroxil” (Poster #SA20), will be presented on Saturday,
March 25, 2017, 12:00 – 2:00 p.m. PT in the Grand Hall. For more
information, including a complete list of abstract titles, please visit
the ICOSR website at http://www.schizophreniacongress.org/.
In February 2016, Alkermes announced topline data from a randomized,
open-label, PK study evaluating the two-month dosing interval. The
results showed that the 1064 mg dose of ARISTADA achieved
therapeutically relevant plasma concentrations of aripiprazole with a PK
profile that supports dosing once every two months. The most common
adverse event in the study for the two-month dosing interval was
injection site pain.
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
have schizophrenia,1 with men and women affected equally.
Worldwide, it is estimated that one person in every 100 develops
schizophrenia, which is one of the most serious types of mental illness.
is an injectable atypical antipsychotic with one-month and six-week
dosing options for the treatment of schizophrenia. ARISTADA is
administered by a healthcare professional. Once in the body, ARISTADA
converts to aripiprazole. ARISTADA was approved by the FDA in October
INDICATION and IMPORTANT SAFETY INFORMATION for ARISTADA® (aripiprazole
lauroxil) extended-release injectable suspension, for intramuscular use
ARISTADA is indicated for the treatment of schizophrenia.
IMPORTANT SAFETY INFORMATION
WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH
Elderly patients with dementia-related psychosis treated with
antipsychotic drugs are at an increased risk of death. ARISTADA is not
approved for the treatment of patients with dementia-related psychosis.
Contraindication: Known hypersensitivity reaction to
aripiprazole. Reactions have ranged from pruritus/urticaria to
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 is not approved for the treatment of patients with
Neuroleptic Malignant Syndrome (NMS): A potentially fatal symptom
complex sometimes referred to as NMS may occur with administration of
antipsychotic drugs, including 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 should be consistent with the need to
minimize TD. Discontinue ARISTADA if clinically appropriate. There is no
known treatment for established TD, although the syndrome 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 ARISTADA 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 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. Patients with a
history of clinically significant low white blood cell count
(WBC)/absolute neutrophil count (ANC) and history of drug-induced
leukopenia/neutropenia should have frequent complete blood count (CBC)
during the first few months of receiving ARISTADA. Consider
discontinuation of ARISTADA at the first sign of a clinically
significant decline in WBC count in the absence of other causative
factors. Monitor patients with clinically significant neutropenia for
fever or other symptoms or signs of infection and treat promptly if such
symptoms or signs occur. Discontinue ARISTADA in patients with severe
neutropenia (absolute neutrophil count <1000/mm3) and
follow their WBC until recovery.
Seizures: ARISTADA should be used with caution in patients with a
history of seizures or with conditions that lower the seizure threshold.
Potential for Cognitive and Motor Impairment: ARISTADA may impair
judgment, thinking, or motor skills. Patients should be cautioned about
operating hazardous machinery, including automobiles, until they are
certain 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
Dysphagia: Esophageal dysmotility and aspiration have been
associated with antipsychotic drug use; use caution in patients at risk
for aspiration pneumonia.
Concomitant Medication: Decreasing the ARISTADA dosage is
recommended in patients taking strong CYP3A4 inhibitors and/or strong
CYP2D6 inhibitors for longer than 2 weeks. Increasing the ARISTADA
dosage is recommended in patients taking CYP3A4 inducers for longer than
2 weeks. No ARISTADA dosage changes are recommended for patients taking
CYP450 modulators for less than 2 weeks.
Most Commonly Observed Adverse Reaction: The most common adverse
reaction (≥5% incidence and at least twice the rate of placebo in
patients treated with ARISTADA) was akathisia.
Injection-Site Reactions: Injection-site reactions were reported
by 4%, 5%, and 2% of patients treated with 441 mg ARISTADA, 882 mg
ARISTADA, 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 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 and any potential adverse effects on the infant from
ARISTADA or from the underlying maternal condition.
Please see FULL
PRESCRIBING INFORMATION, including Boxed Warning for
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
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: decisions by the FDA relating to the
sNDA submission for the two-month dosing option of ARISTADA; and the
therapeutic value, development plans and commercial potential of the
two-month dosing option of ARISTADA. 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: adverse decisions by regulatory
authorities may occur; the two-month dosing option of ARISTADA could be
ineffective or unsafe; the company may be unable to commercially
manufacture the two-month dosing option of ARISTADA successfully; and
those risks described in the Alkermes plc Annual Report on Form 10-K for
the fiscal year ended Dec. 31, 2016, and in other 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.
The information contained in this press release is provided by the
company as of the date hereof, and, except as required by law, the
company disclaims any intention or responsibility for updating or
revising any forward-looking information contained in this press release.
ARISTADA® is a registered trademark of Alkermes Pharma
1 National Institutes of Health. Schizophrenia.
Accessed on March 17, 2017 from http://report.nih.gov/NIHfactsheets/ViewFactSheet.aspx?csid=67&key=S#S
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Source: Alkermes plc
Eva Stroynowski, +1 781-609-6823
Coombs, +1 781-609-6377
Lindsey Smith, +1