— Initiation With Aripiprazole Lauroxil NanoCrystal Dispersion®
Designed to Replace Need for Concomitant Three Weeks of Oral
Aripiprazole With First ARISTADA Dose —
— FDA Action Expected by June 30, 2018 —
DUBLIN--(BUSINESS WIRE)--Nov. 16, 2017--
plc (NASDAQ: ALKS) today announced that the New Drug Application
(NDA) for Aripiprazole Lauroxil NanoCrystal®
Dispersion (ALNCD), a novel, investigational product designed
for initiation onto ARISTADA® (aripiprazole lauroxil)
extended-release injectable suspension for the treatment of
schizophrenia, has been accepted for filing by the U.S. Food and Drug
Administration (FDA). The FDA has issued a target action date for the ALNCD
NDA of June 30, 2018 under the Prescription Drug User Fee Act (PDUFA).
“The acceptance of this filing marks a significant milestone as we seek
approval for Aripiprazole Lauroxil NanoCrystal Dispersion as
a novel product designed for initiation onto ARISTADA for the treatment
of schizophrenia,” said Elliot Ehrich, M.D., Executive Vice President,
Research and Development of Alkermes. “We look forward to working with
the Agency in the coming months with the goal of bringing this potential
new initiation product for ARISTADA to healthcare providers and their
patients as quickly as possible.”
If approved, administration of ALNCD in conjunction with a
single oral dose of 30 mg aripiprazole will replace the need for three
weeks of concomitant oral aripiprazole with the first dose of ARISTADA.
The ALNCD investigational product is designed for initiation
onto any dose or duration of ARISTADA (441 mg, 662 mg or 882 mg monthly,
882 mg once every six weeks, and 1064 mg once every two months).
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 have schizophrenia,1 with men and
women affected equally.
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.
Oral aripiprazole should be administered for 21 consecutive days in
conjunction with the first injection of ARISTADA. A New Drug Application
(NDA) for Aripiprazole Lauroxil NanoCrystal® Dispersion (ALNCD),
an investigational product designed for initiation onto ARISTADA, is
under review by the U.S. Food and Drug Administration (FDA). If
approved, administration of ALNCD in conjunction with a
single oral dose of 30 mg aripiprazole will provide an alternative to
the three weeks of concomitant oral aripiprazole with the first dose of
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
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. 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 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 from 441 mg to 662 mg 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 reported
by patients treated with ARISTADA 441 mg and 882 mg monthly) was
Injection-Site Reactions: 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 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: the company’s expectations and
timeline for regulatory action by the FDA relating to the NDA submission
for ALNCD for the treatment of schizophrenia; approval by
the FDA of the NDA for ALNCD; and the potential
therapeutic and commercial value of ALNCD and 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: whether the NDA for ALNCD
will be approved by the FDA by June 30, 2018 or at all; if approved,
whether ALNCD will be commercialized successfully; whether
ARISTADA or ALNCD could be shown 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,
2016 and Quarterly Reports on Form 10-Q for the quarters ended March 31,
2017 and Sept. 30, 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® and NanoCrystal® are registered
trademarks of Alkermes Pharma Ireland Limited.
1National Institutes of Health. Schizophrenia.
Accessed November 15, 2017 from https://report.nih.gov/nihfactsheets/ViewFactSheet.aspx?csid=67.
View source version on businesswire.com: http://www.businesswire.com/news/home/20171116005137/en/
Source: Alkermes plc
Stroynowski, +1 781-609-6823
Sandy Coombs, +1 781-609-6377
Lindsey Smith, +1 781-609-6231