TITUSVILLE, N.J., March 29, 2015 /PRNewswire/ -- Three-month
paliperidone palmitate, an investigational atypical antipsychotic,
significantly delayed time to relapse compared to placebo in
patients with schizophrenia, according to a new Phase 3 clinical
study published this week in the Journal of the American Medical
Association (JAMA) Psychiatry. Results of the study
served as the basis for the recent New Drug Application (NDA)
filing for three-month paliperidone palmitate injection to treat
schizophrenia in adults with the U.S. Food and Drug Administration
("FDA") by Janssen Research & Development, LLC, ("Janssen"),
the study sponsor. The FDA granted the filing Priority Review
status in January, with a regulatory action date of May 18, 2015.
If approved, the treatment would enable patients to receive
injections once every three months, compared to currently available
formulations that are administered monthly, or oral medicines that
must be taken daily. It would be the first and only long-acting
atypical antipsychotic with a dosing schedule of four times a year.
Janssen plans filings for three-month paliperidone palmitate in
many markets outside of the U.S. later this year.
The final published analysis results are consistent with
previously announced interim analysis results which showed a
statistically significant benefit of three-month paliperidone
palmitate compared to placebo. In March
2014, following an Independent Data Monitoring Committee
(IDMC) recommendation based on positive efficacy, Janssen halted
this study early.
The study data also are being presented this week at the
23rd annual European Congress of Psychiatry in
Vienna, Austria, and at the
15th annual International Congress on Schizophrenia
Research in Colorado Springs,
Colorado.
"There remains significant unmet need for the approximately 2.4
million people in the United
States who live with schizophrenia. The results of this
study reinforce the need for this unprecedented treatment option
for patients with schizophrenia who may benefit from a new, less
frequently dosed treatment choice," said Husseini K. Manji, MD, Global Head, Neuroscience
Therapeutic Area, Janssen. "We look forward to continuing to work
with the FDA and other regulatory authorities to bring this
innovative three-month formulation to patients as soon as
possible."
"Physicians need a broad range of treatments to help patients
with schizophrenia early in the course of their disease," said
David Hough, MD, Schizophrenia
Disease Area Leader, Janssen, a study author. "This clinical trial
showed three-month paliperidone palmitate demonstrated a
statistically significant difference from placebo in delaying time
to relapse, validating its potential as a new treatment option
which could positively affect the care of people with
schizophrenia."
This Phase 3, international, randomized, multicenter,
double-blind, placebo-controlled, relapse prevention study
evaluated 305 adults in the double-blind phase. There were 160
study patients in the three-month paliperidone palmitate treatment
group and 145 patients in the placebo group. All of the patients
enrolled in the study met the DSM-IV diagnosis of schizophrenia and
had a Positive and Negative Syndrome Scale (PANSS) total score of
less than 120 at screening and baseline. Prior to randomization,
individuals were first stabilized with INVEGA SUSTENNA®
(paliperidone palmitate) one-month formulation during a 17-week,
open-label transition period. Patients who met criteria for
clinical stability then received a single three-month paliperidone
palmitate injection during a 12-week, open-label maintenance phase.
Stable patients were then randomized to treatment with either
three-month paliperidone palmitate or placebo. Patients remained in
the double-blind phase until they relapsed, withdrew from the
study, or the study terminated.
Relapse was defined as worsening schizophrenia symptoms as
determined by PANSS assessment criteria, hospitalization for
schizophrenia symptoms, clinically significant self-injury,
suicidal or homicidal ideation or violent behavior.
After the first 42 relapse events occurred in the double-blind
phase, a pre-specified interim analysis overseen by an IDMC showed
that three-month paliperidone palmitate significantly delayed time
to relapse compared to placebo (hazard ratio [HR] 3.45; 95% CI:
1.73-6.88; p=0.0002; median time to relapse for placebo group: 274
days). While there were 11 relapses in the three-month paliperidone
palmitate treatment group, these were too few to provide a reliable
estimate of the duration of time until relapse for that group of
patients. Final analysis results were consistent with that of the
interim analysis, confirming three-month paliperidone palmitate's
superiority over placebo for delaying time to relapse of
schizophrenia symptoms (HR 3.81; 95% CI: 2.08-6.99; p<0.0001;
median time to relapse for placebo group: 395 days, and three-month
paliperidone palmitate group: not estimable).
In this study, the most common treatment-emergent adverse events
(TEAEs), which occurred in at least 3% of patients in the
double-blind phase of the study and that occurred more frequently
in the three-month paliperidone palmitate group than placebo group,
were headache (9% vs. 4%), increased weight (9% vs. 3%),
nasopharyngitis (6% vs. 1%) and akathisia, a movement disorder (4%
vs. 1%). During the double-blind phase, a total of 6 patients (4%)
in the three-month paliperidone palmitate group reported injection
site-related TEAEs; of which, injection site pain (2 patients [1%])
was most frequently reported. Prolactin-related TEAEs occurred in 1
of 42 female patients in the three-month paliperidone palmitate
group (2%). Serious TEAEs occurred 4 times more often in the
placebo group than in the three-month paliperidone palmitate group
(10% vs. 3%), and were mostly related to an increase in psychiatric
symptoms reflecting the course of the underlying disease.
INVEGA SUSTENNA® (paliperidone
palmitate) was approved by the U.S. FDA in July 2009 as
the first once-monthly atypical long-acting injection to treat
schizophrenia and is now approved in more than 80 countries. Late
last year the FDA approved
INVEGA SUSTENNA® for the treatment of
schizoaffective disorder, making it the first and only once-monthly
medication to treat this condition. INVEGA SUSTENNA® and
three-month paliperidone palmitate utilize Alkermes' proprietary
NanoCrystal® technology, which enables solubility of
poorly water-soluble compounds.
For additional study information, visit ClinicalTrials.gov.
About INVEGA SUSTENNA®
INVEGA
SUSTENNA® (paliperidone palmitate) was approved by the
U.S. FDA in July 2009 as the first
once-monthly atypical long-acting injection to treat schizophrenia
and is now approved in more than 80 countries. Late last year the
FDA approved INVEGA SUSTENNA® for the treatment of
schizoaffective disorder, making it the first and only once-monthly
medication to treat this condition. INVEGA SUSTENNA® and
three-month paliperidone palmitate utilize Alkermes' proprietary
NanoCrystal® technology, which enables solubility of
poorly water-soluble compounds.
About Schizophrenia
Schizophrenia is a complex and
chronic brain disorder that can be severe and disabling. It affects
approximately 2.4 million U.S. adults, often beginning in the late
teens or early 20s. The disease typically manifests as
hallucinations, delusions, and disorganized thoughts and behavior.
Because there are currently no physical or laboratory tests that
diagnose this condition, schizophrenia is diagnosed by the presence
of symptoms. Researchers have identified various risk factors for
this disease, including heredity and certain genetic risk factors,
and environmental factors, such as social stress, isolation and
drug use. If left untreated, schizophrenia can greatly interfere
with education, employment and interpersonal functioning. The
course of schizophrenia is varied, generally involving a series of
relapses or the return of disease after partial recovery.
About Janssen Research & Development, LLC
Janssen
Research & Development, LLC, is headquartered in Raritan, N.J., and has affiliated facilities
in Europe, the United States and Asia. Driven by its commitment to patients,
Janssen Research & Development works to bring innovative ideas,
products, services and solutions to address serious unmet medical
needs around the world. The company is leveraging a combination of
internal and external innovation to discover and develop novel
medicines and solutions in five distinct therapeutic areas:
Neuroscience, Oncology, Immunology, Infectious Diseases and
Vaccines, and Cardiovascular and Metabolism. For more information
about Janssen Research & Development, LLC visit
www.janssenrnd.com.
About Janssen Pharmaceuticals, Inc.
Janssen
Pharmaceuticals, Inc. is dedicated to addressing and resolving the
major unmet medical needs of our time. Also driven by its
commitment to patients, healthcare professionals, and caregivers,
Janssen strives to develop sustainable and integrated healthcare
solutions by working in partnership with all stakeholders on the
basis of trust and transparency. The company's daily work is guided
by meeting goals of excellence in quality, innovation, safety and
efficacy in order to advance patient care. Janssen provides
medicines for an array of illnesses and disorders in several
therapeutic areas. For more information on Janssen Pharmaceuticals,
Inc., visit www.JanssenPharmaceuticalsInc.com or follow Janssen on
Twitter at www.twitter.com/JanssenUS and on YouTube at
https://www.youtube.com/user/JanssenUS.
Janssen Pharmaceuticals, Inc. and Janssen Research &
Development, LLC are part of the Janssen Pharmaceutical Companies
of Johnson & Johnson. Janssen Pharmaceuticals, Inc. markets
INVEGA SUSTENNA® in the United
States.
INVEGA SUSTENNA® (paliperidone palmitate) is
indicated for the treatment of:
- Schizophrenia.
- Schizoaffective disorder as monotherapy and as an adjunct to
mood stabilizers or antidepressants.
IMPORTANT SAFETY INFORMATION FOR INVEGA
SUSTENNA® (paliperidone palmitate)
WARNING: INCREASED
MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED
PSYCHOSIS.
|
See full
Prescribing Information for complete Boxed Warning
|
- Elderly patients with
dementia-related psychosis treated with antipsychotic drugs are at
an increased risk of death.
- INVEGA®
SUSTENNA® is not approved for the treatment of patients
with dementia-related psychosis.
|
|
Contraindications: Paliperidone is contraindicated in
patients with a known hypersensitivity to either paliperidone,
risperidone, or to any excipients of the formulation.
Cerebrovascular Adverse Reactions: Cerebrovascular
adverse reactions (e.g., stroke, transient ischemic attacks),
including fatalities, were reported in placebo-controlled trials in
elderly patients with dementia-related psychosis taking oral
risperidone, aripiprazole, and olanzapine. The incidence of
cerebrovascular adverse reactions was significantly higher than
with placebo. INVEGA SUSTENNA® is not approved for the
treatment of patients with dementia-related psychosis.
Neuroleptic Malignant Syndrome (NMS): NMS, a potentially
fatal symptom complex, has been reported with the use of
antipsychotic medications, including paliperidone. Clinical
manifestations include muscle rigidity, fever, altered mental
status, and evidence of autonomic instability (see full Prescribing
Information). Management should include immediate discontinuation
of antipsychotic drugs and other drugs not essential to concurrent
therapy, intensive symptomatic treatment and close medical
monitoring, and treatment of any concomitant serious medical
problems.
QT Prolongation: Paliperidone causes a modest increase in
the corrected QT (QTc) interval. Avoid the use of drugs that
also increase QTc interval and in patients with risk factors for
prolonged QTc interval. Paliperidone should also be avoided in
patients with congenital long QT syndrome and in patients with a
history of cardiac arrhythmias. Certain circumstances may increase
the risk of the occurrence of torsades de pointes and/or sudden
death in association with the use of drugs that prolong the QTc
interval.
Tardive Dyskinesia (TD): TD is a syndrome of potentially
irreversible, involuntary, dyskinetic movements that may develop in
patients treated with antipsychotic medications. The risk of
developing TD and the likelihood that dyskinetic movements will
become irreversible are believed to increase with duration of
treatment and total cumulative dose, but can develop after
relatively brief treatment at low doses. Elderly female patients
appeared to be at increased risk for TD, although it is impossible
to predict which patients will develop the syndrome. Prescribing
should be consistent with the need to minimize the risk of TD (see
full Prescribing Information). Discontinue drug if clinically
appropriate. The syndrome may remit, partially or completely, if
antipsychotic treatment is withdrawn.
Metabolic Changes: Atypical antipsychotic drugs
have been associated with metabolic changes that may increase
cardiovascular/cerebrovascular risk. These metabolic changes
include hyperglycemia, dyslipidemia, and body weight gain. While
all of the drugs in the class have been shown to produce some
metabolic changes, each drug has its own specific risk profile.
Hyperglycemia and Diabetes Mellitus: Hyperglycemia and
diabetes mellitus, in some cases extreme and associated with
ketoacidosis, hyperosmolar coma or death, have been reported in
patients treated with all atypical antipsychotics (APS). Patients
starting treatment with APS who have or are at risk for diabetes
mellitus should undergo fasting blood glucose testing at the
beginning of and during treatment. Patients who develop symptoms of
hyperglycemia during treatment should also undergo fasting blood
glucose testing. All patients treated with atypical antipsychotics
should be monitored for symptoms of hyperglycemia. Some patients
require continuation of antidiabetic treatment despite
discontinuation of the suspect drug.
Dyslipidemia: Undesirable alterations 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.
Orthostatic Hypotension and Syncope: INVEGA
SUSTENNA® may induce orthostatic hypotension in some
patients due to its alpha-blocking activity. INVEGA
SUSTENNA® should be used with caution in patients with
known cardiovascular disease, cerebrovascular disease or conditions
that would predispose patients to hypotension (e.g., dehydration,
hypovolemia, treatment with antihypertensive medications).
Monitoring should be considered in patients for whom this may be of
concern.
Leukopenia, Neutropenia and Agranulocytosis have been
reported with antipsychotics, including paliperidone. Patients with
a history of clinically significant low white blood cell count
(WBC) or drug-induced leukopenia/neutropenia should have frequent
complete blood cell counts during the first few months of therapy.
At the first sign of a clinically significant decline in WBC, and
in the absence of other causative factors, discontinuation of
INVEGA SUSTENNA® should be considered. Patients with
clinically significant neutropenia should be carefully monitored
for fever or other symptoms or signs of infection and treated
promptly if such symptoms or signs occur. Patients with severe
neutropenia (absolute neutrophil count <1000/mm3)
should discontinue INVEGA SUSTENNA® and have their WBC
followed until recovery.
Hyperprolactinemia: As with other drugs that antagonize
dopamine D2 receptors, INVEGA SUSTENNA®
elevates prolactin levels, and the elevation persists during
chronic administration. Paliperidone has a prolactin-elevating
effect similar to risperidone, which is associated with higher
levels of prolactin elevation than other antipsychotic agents.
Potential for Cognitive and Motor Impairment: Somnolence,
sedation, and dizziness were reported as adverse reactions in
subjects treated with INVEGA SUSTENNA®. INVEGA
SUSTENNA® has the potential to impair judgment,
thinking, or motor skills. Patients should be cautioned about
performing activities that require mental alertness such as
operating hazardous machinery, including motor vehicles, until they
are reasonably certain that INVEGA SUSTENNA® does not
adversely affect them.
Seizures: INVEGA SUSTENNA® should be used
cautiously in patients with a history of seizures or with
conditions that potentially lower seizure threshold. Conditions
that lower seizure threshold may be more prevalent in patients 65
years or older.
Administration: For intramuscular injection only by a
healthcare professional. Care should be taken to avoid inadvertent
injection into a blood vessel.
Drug Interactions: Strong CYP3A4/P-glycoprotein (P-gp)
inducers: It may be necessary to increase the dose of INVEGA
SUSTENNA® when a strong inducer of both CYP3A4
and P-gp (e.g. carbamazepine, rifampin, St. John's wort) is co-administered.
Conversely, on discontinuation of the strong inducer, it may be
necessary to decrease the dose of INVEGA SUSTENNA®.
Pregnancy/Nursing: Patients should be advised to notify
their physician if they become pregnant/intend to become pregnant
or intend to nurse during treatment with INVEGA
SUSTENNA®.
Commonly Observed Adverse Reactions for INVEGA
SUSTENNA®: The most common adverse reactions
in clinical trials in patients with schizophrenia (≥5% and twice
placebo) were injection site reactions, somnolence/sedation,
dizziness, akathisia and extrapyramidal disorder. No adverse events
occurred at a rate of ≥5% and twice placebo during the long-term
double-blind, placebo-controlled study in patients with
schizoaffective disorder. The following adverse reactions
occurred more frequently (a ≥2% difference vs. placebo) in the
long-term study in patients with schizoaffective disorder: weight
increased, nasopharyngitis, headache, hyperprolactinemia, and
pyrexia.
Please see full Prescribing Information including Boxed Warning
for INVEGA SUSTENNA® (paliperidone palmitate) and
INVEGA® (paliperidone)
at www.JanssenCNS.com/InvegaSustenna and
www.JanssenCNS.com/Invega.
(This press release contains "forward-looking statements" as
defined in the Private Securities Litigation Reform Act of 1995
regarding product development. The reader is cautioned not to rely
on these forward-looking statements. These statements are based on
current expectations of future events. If underlying assumptions
prove inaccurate or known or unknown risks or uncertainties
materialize, actual results could vary materially from the
expectations and projections of Janssen Research & Development,
LLC and/or Johnson & Johnson. Risks and uncertainties include,
but are not limited to: challenges inherent in new product
development, including obtaining regulatory approvals; competition,
including technological advances, new products and patents attained
by competitors; challenges to patents; changes to applicable laws
and regulations, including global health care reforms; and trends
toward health care cost containment. A further list and description
of these risks, uncertainties and other factors can be found in
Johnson & Johnson's Annual Report on Form 10-K for the fiscal
year ended December 28, 2014,
including in Exhibit 99 thereto, and the company's subsequent
filings with the Securities and Exchange Commission. Copies of
these filings are available online
at www.sec.gov, www.jnj.com or
on request from Johnson & Johnson. None of the Janssen
Pharmaceutical Companies or Johnson & Johnson undertakes to
update any forward-looking statement as a result of new information
or future events or developments.
Media Contact:
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Panico
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908-240-2011 (mobile)
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