-- Large, randomized ALPINE trial showed both long-acting
injectable medications effectively controlled schizophrenia
symptoms throughout six-month study --
-- ARISTADA demonstrated significant and similar efficacy to
current market-leader INVEGA SUSTENNA, with differences in safety
and tolerability parameters --
-- Data provide clinical evidence of efficacy,
safety and tolerability of ARISTADA INITIO® and
once-every-two-month ARISTADA dosing regimen, with
favorable overall retention rate in study --
DUBLIN, April 9, 2019 /PRNewswire/
-- Alkermes plc (Nasdaq: ALKS) today announced
positive topline results from ALPINE (Aripiprazole
Lauroxil and Paliperidone palmitate:
INitiation Effectiveness), a first-of-its-kind,
six-month study evaluating the efficacy, safety and tolerability of
ARISTADA® (aripiprazole lauroxil) and INVEGA
SUSTENNA® (paliperidone palmitate) when used to
initiate patients experiencing an acute exacerbation of
schizophrenia in the hospital and maintain treatment in an
outpatient setting. Patients randomized to the ARISTADA treatment
group were initiated using the ARISTADA INITIO®
regimen* followed by ARISTADA (1064 mg) every two months. Patients
randomized to the INVEGA SUSTENNA treatment group were initiated
using a loading dose of INVEGA SUSTENNA (234 mg) followed by INVEGA
SUSTENNA (156 mg) every month.
"The ALPINE study showed that both ARISTADA, given every two
months, and INVEGA SUSTENNA, given every month, demonstrated
statistically significant improvements from baseline in
schizophrenia symptoms, and that the efficacy was similar for both
medicines throughout the six-month study. This research provides
evidence that these two long-acting medicines, each with their own
distinct safety and tolerability profile, may be clinically useful
in helping to bridge the critical transition between inpatient and
outpatient settings of care," said Craig
Hopkinson, M.D., Chief Medical Officer at Alkermes. "These
data underscore that ARISTADA INITIO along with the two-month dose
of ARISTADA together represent a novel approach to treatment
initiation and a compelling clinical option for patients and
healthcare professionals alike. The ALPINE study illustrates
Alkermes' commitment to expanding the body of evidence for
schizophrenia treatment and developing important medicines that
help meet critical unmet needs in patient care."
The ALPINE study met its pre-specified primary endpoint,
demonstrating that both ARISTADA and INVEGA SUSTENNA had
statistically significant and clinically meaningful reductions in
Positive and Negative Syndrome Scale (PANSS) total scores from
baseline at Week 4 (ARISTADA group: -17.4 points, p<0.001;
INVEGA SUSTENNA group: -20.1 points, p<0.001). Additionally,
PANSS total scores continued to improve at Week 9 and Week 25, the
study's pre-specified secondary endpoints (ARISTADA group: -19.8
points, p<0.001 at Week 9 and -23.3 points, p<0.001 at Week
25; INVEGA SUSTENNA group: -22.5 points, p<0.001 at Week 9 and
-21.7 points, p<0.001 at Week 25). Improvements in PANSS total
scores from baseline were similar and not statistically different
between treatment groups at any assessment time point during the
study.
The most common adverse events reported in the ARISTADA
treatment group were injection site pain (17.2%), increase in
weight (9.1%) and akathisia (9.1%). The most common adverse
events reported in the INVEGA SUSTENNA treatment group were
injection site pain (24.8%), increase in weight (16.8%) and
akathisia (10.9%). Overall, 56.6% of patients in the ARISTADA
treatment group and 42.6% of patients in the INVEGA SUSTENNA
treatment group completed the six-month study.
"People living with schizophrenia face a complex treatment
system and countless challenges that can disrupt continuity of care
and make them vulnerable to relapse and re-hospitalization," said
Dr. Jelena Kunovac, founder and
president, Altea Research, and ALPINE study investigator. "The
results from ALPINE validate the role that long-acting atypical
antipsychotics can play in rapidly and effectively stabilizing
patients in the hospital and supporting their continuity of care
after discharge. The ability to start and stay on effective
medication is essential to helping patients and caregivers achieve
long-term treatment goals."
Alkermes expects to submit results from the ALPINE study to
peer-reviewed journals for publication and present full study
results, including efficacy, safety, tolerability and exploratory
analyses, at upcoming scientific meetings.
ALPINE Study Design
ALPINE was a multicenter,
randomized, double-blind, phase 3b
study evaluating the efficacy, safety and tolerability of ARISTADA
and INVEGA SUSTENNA in 200 subjects experiencing an acute
exacerbation of schizophrenia. The study included a two-week
inpatient phase, during which all subjects were initiated onto
either ARISTADA or INVEGA SUSTENNA, followed by an outpatient phase
for a total of six months. Patients randomized to the ARISTADA
treatment group were initiated using the ARISTADA INITIO
regimen—comprised of ARISTADA INITIO (675 mg) in combination with a
single 30 mg oral dose of aripiprazole—on day 1, followed by
ARISTADA (1064 mg) on day 8 and every two months thereafter.
Patients randomized to the INVEGA SUSTENNA treatment group received
an initiation dose of INVEGA SUSTENNA (234 mg) on day 1, followed
by INVEGA SUSTENNA (156 mg) on day 8 and every month
thereafter.
The study's pre-specified primary endpoint was the change from
baseline in Positive and Negative Syndrome Scale (PANSS) total
scores at Week 4 within each treatment group. Pre-specified
secondary endpoints included the change from baseline in PANSS
total scores at Week 9 and Week 25 within each treatment group, as
well as between treatment group comparisons at Week 4, Week 9 and
Week 25. PANSS is a standard psychiatric scale used for
measuring symptom severity in schizophrenia.
About Schizophrenia
Schizophrenia is a complex and often difficult-to-treat disease
that affects more than 2.4 million people in the U.S.,1
contributes to more than 800,000 hospital admissions each
year2 and results in an estimated $32-65 billion in treatment and other economic
costs annually.3 One study of adults hospitalized with
schizophrenia found that approximately 40 percent did not receive
any outpatient follow-up care within 30 days of discharge
4 and another found that among patients who are
hospitalized and discharged, more than 15 percent are readmitted
within 30 days.5 Long-acting therapies for schizophrenia
may help eliminate the burden of taking a daily oral antipsychotic
and support medication adherence,6 which is a key factor
in risk of relapse.7 However, despite research
demonstrating the benefits of long-acting injectable antipsychotics
(LAIs), including potential improvements in
symptoms,6 only 11 percent of patients with
schizophrenia in the U.S. are treated with LAIs.8
About ARISTADA INITIO®
ARISTADA
INITIO, in combination with a single 30 mg dose of oral
aripiprazole, is indicated for the initiation of ARISTADA when
used for the treatment of schizophrenia in adults and can be used
to initiate patients onto any dose of ARISTADA. The first ARISTADA
dose may be administered on the same day as the ARISTADA INITIO
regimen or up to 10 days thereafter.
About ARISTADA®
ARISTADA is an
injectable atypical antipsychotic approved in the U.S. 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 in
adults.
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
in contrast to ARISTADA which is administered monthly, every
6 weeks, or every 8 weeks. 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 strong CYP3A4 inhibitors, strong CYP2D6 inhibitors, or
strong CYP3A4 inducers for greater than 2 weeks. Avoid
use of ARISTADA 662mg, 882mg, 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 441mg 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
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, multiple sclerosis and oncology. 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 potential
therapeutic and commercial value of LAIs, of ARISTADA, and of the
ARISTADA INITIO regimen for initiation onto ARISTADA, for the
treatment of schizophrenia; and timing and expectations regarding
further reporting, and submission for publication, of the ALPINE
study results. 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 results from the ALPINE study are
predictive of real-world results, 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, 2018 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.
*The ARISTADA INITIO regimen is comprised of ARISTADA INITIO
(675 mg) + a single 30 mg oral dose of aripiprazole, and provides
an alternative to the concomitant three weeks of oral aripiprazole
for initiation onto ARISTADA.
ARISTADA® and ARISTADA INITIO® are
registered trademarks of Alkermes Pharma Ireland Limited.
INVEGA SUSTENNA® is a registered trademark
of Johnson & Johnson.
1 National Institutes of Health. 2010.
Schizophrenia Fact Sheet.
https://report.nih.gov/NIHfactsheets/Pdfs/Schizophrenia(NIMH).pdf. Accessed
April 8, 2019.
2 Saba DK, Levit KR, Elixhauser A. Healthcare
Cost and Utilization Project (HCUP) Statistical Briefs Hospital
Stays Related to Mental Health, 2006 Statistical Brief #62 2006,
Page 12, Figure 1
3 Schizophrenia and Related Disorders Alliance
of America,
https://sardaa.org/resources/about-schizophrenia/ accessed on
April 8, 2019.
4 Olfson, M., Marcus, SC. and Doshi, JA.
Continuity of Care After Inpatient Discharge of Patients with
Schizophrenia in the Medicaid Program: A Retrospective Longitudinal
Cohort Analysis. J Clin Psychiatry. 2010 Jul;71(7):831-8. doi:
10.4088/JCP.10m05969yel
5 Heslin KC, Weiss AJ. Hospital Readmissions
Involving Psychiatric Disorders, 2012. HCUP Statistical Brief #189.
May 2015.
http://www.hcup-us.ahrq.gov/reports/statbriefs/sb189-Hospital-Readmissions-Psychiatric-Disorders-2012.pdf
6 Lehman, A., Lieberman, J., et al. Practice
Guideline for the Treatment of Patients with Schizophrenia; Second
Edition. American Psychiatric Association, 2010
7 Emsley, R., Chiliza, B., Asmal, L., &
Harvey, B. H. The nature of relapse in schizophrenia. BMC
psychiatry, 2013;13(1), 50
8 IQVIA NSP & Custom SOB data sets R12M
ending September 2018
Alkermes
Contacts:
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For
Investors:
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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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