- Switching to UZEDY at four weeks after the last dose of
once-monthly paliperidone palmitate provided the most comparable
pharmacokinetic (PK) profile based on the relevant PK modeling
data
- Additional data include new Phase 3 RISE and SHINE analyses
demonstrating no new or unexpected safety concerns in young adults
with schizophrenia treated with UZEDY
- Global ADVANCE survey findings also reveal real-world
experiences and perspectives on long-acting injectable (LAI)
schizophrenia treatments from healthcare professionals, caregivers
and patients
Teva Pharmaceuticals, a U.S. affiliate of Teva Pharmaceutical
Industries Ltd. (NYSE and TASE: TEVA), today announced the
presentation of seven studies from its long-acting injectable (LAI)
schizophrenia research program. Presentations include data
informing clinical strategies for switching patients to UZEDY, an
extended-release injectable suspension of risperidone for
subcutaneous use every one or two months for the treatment of
schizophrenia in adults, from a once-monthly intramuscular
injection of Invega Sustenna. The results were presented at the
Psych Congress Elevate 2024 Annual Meeting taking place from May 30
– June 2 in Las Vegas, Nevada.
“UZEDY is a long-acting formulation of risperidone with an
innovative delivery system that requires no loading dose or oral
supplementation and can be dosed at one- or two-month intervals to
help with prevention of relapse. It is administered subcutaneously
under the skin instead of intramuscularly, which is an important
feature to discuss with patients,” said Eric Hughes, MD, PhD,
Executive Vice President of Global R&D and Chief Medical
Officer at Teva. “We are proud to share these clinical insights
that may help healthcare providers understand more about switching
between long-acting options for their schizophrenia patients.”
In a population pharmacokinetic (PopPK) analysis, simulations
were performed to predict PK exposures when switching to UZEDY 4 -
6 weeks at steady state after the last injection of once-monthly
paliperidone palmitate. Model simulations showed that switching to
UZEDY at four weeks after the last dose of once-monthly
paliperidone palmitate yielded generally higher PK parameters, both
within the total active moiety range for oral risperidone.
Comparable doses included UZEDY at 125 mg (once-monthly dosing) or
250 mg (once-every-two-months dosing) to 234 mg of once-monthly
paliperidone palmitate. The analysis aims to address the knowledge
gap as limited clinical data currently exist to inform strategies
for switching between the various available LAI treatment options
with differing PK properties.1
Any switching strategy should be determined by clinicians on an
individual basis, considering factors such as patient preference,
scheduling convenience and potential tolerability issues or risk of
symptom breakthrough.
“The treatment and management of schizophrenia is a journey and
many patients may see their needs evolve over time due to
challenges with symptom control or simply due to a change in dosing
preference,” said Christoph Correll, MD, Professor of Psychiatry at
the Zucker School of Medicine, Hempstead, NY. “Researchers and
clinicians like myself rely on analyses like these to understand
strategies for switching between long-acting injectable options and
help ensure each of our patients is on the most appropriate
treatment.”
Additional key data being presented at Psych Congress Elevate
2024:
New data from the RISE (Risperidone Subcutaneous
Extended-Release Study) and SHINE (A Study to Test TV-46000 for
Maintenance Treatment of Schizophrenia) Phase 3 pivotal studies
that supported the FDA approval of UZEDY for adults. The updated
analysis evaluated the safety of once or twice monthly UZEDY for
young adults (aged 18-21) who participated in the RISE and SHINE
studies. No unexpected safety concerns or clinically meaningful
trends in adverse events were observed.1
Qualitative data from four ADVANCE (Attitudes Driving Regional
Differences in LAI Antipsychotic Utilization for Schizophrenia
Among Healthcare Professionals, Patients and Caregivers) surveys
showing:
- Ten psychiatrists, who average 18 years of experience and spend
45% of their practice time in hospital-based outpatient clinics,
were interviewed and expressed that treatment priorities for
patients with schizophrenia may differ depending on the care
setting, but all described the potential benefits of LAIs for both
patients and clinicians. 1
- Seven psychiatric nurses, who average 17 years of experience
and spend 47% of their practice time in outpatient clinics, were
interviewed and expressed positive views of LAIs but had a limited
understanding of specific LAI molecules and prioritized the
benefits of LAIs for nonadherent patients, highlighting potential
unmet HCP educational needs. 1
- In the patient and caregiver surveys, 20 patients and 19
caregivers completed a 60-minute interview regarding the use of
LAIs in schizophrenia. Most patient-reported perceptions regarding
advantages of LAIs were convenience (n=7) and fewer side effects
compared with oral antipsychotics (n=3). Caregivers emphasized the
importance of a patient’s quality of life along with symptom
management and expressed advantages of LAIs, including convenience
to both the person with schizophrenia and the caregiver (n=10 and
n=7, respectively). 1
Below is the full set of UZEDY and long-acting injectable data
presented by Teva at Psych Congress Elevate 2024.
UZEDY (risperidone):
- (De novo) Switching Patients With Schizophrenia From
Intramuscular Paliperidone Palmitate Once Monthly to TV-46000, a
Long-Acting Subcutaneous Antipsychotic: An Exploration of
Population Pharmacokinetic-Based Strategies
- (De novo) Safety and Exposure of TV-46000, a Long-Acting
Subcutaneous Antipsychotic (LASCA) Formulation of Risperidone, in
Adolescent and Young Adult Patients With Schizophrenia: Results
From the Phase 3 RISE and SHINE Studies
- (Encore) Switching Patients With Schizophrenia to TV-46000, a
Long-Acting Subcutaneous Antipsychotic, From Risperidone
Microspheres (R064766): An Exploration of Population
Pharmacokinetic-Based Strategies
LAI Real-World Insights:
- (De novo) Experience and Perceptions of Psychiatrists Treating
Schizophrenia With Long-Acting Injectable Antipsychotics:
Qualitative Results From the Multinational ADVANCE Study
- (De novo) Psychiatric Nurse Perceptions of Long-Acting
Injectable Therapies for Treating Schizophrenia: Qualitative
Results From the Multinational ADVANCE Study
- (De novo) Attitudes Driving Regional Differences in LAI
Antipsychotic Utilization for Schizophrenia Among HCPs, Patients
and Caregivers (ADVANCE) Study: Experiences and Perceptions of LAIs
from Caregivers
- (De novo) Attitudes Driving Regional Differences in LAI
Antipsychotic Utilization for Schizophrenia Among HCPs, Patients
and Caregivers (ADVANCE) Study: Patients’ Perspectives on Initial
and Current Treatments
INDICATION AND USAGE
UZEDY (risperidone) extended-release injectable suspension for
subcutaneous use is indicated for the treatment of schizophrenia in
adults.
WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH
DEMENTIA-RELATED PSYCHOSIS
Elderly patients with dementia-related psychosis treated with
antipsychotic drugs are at an increased risk of death. UZEDY is not
approved for use in patients with dementia-related psychosis and
has not been studied in this patient population.
See below for additional Important Safety Information.
About Schizophrenia
Schizophrenia is a chronic, progressive and severely
debilitating mental disorder that affects how one thinks, feels and
acts.2 Patients experience an array of symptoms, which may include
delusions, hallucinations, disorganized speech or behavior and
impaired cognitive ability.2,3,4 Approximately 1% of the world’s
population will develop schizophrenia in their lifetime, and 3.5
million people in the U.S. are currently diagnosed with the
condition.3,4 Although schizophrenia can occur at any age, the
average age of onset tends to be in the late teens to the early 20s
for men, and the late 20s to early 30s for women.4 The long-term
course of schizophrenia is marked by episodes of partial or full
remission broken by relapses that often occur in the context of
psychiatric emergency and require hospitalization.4 Approximately
80% of patients experience multiple relapses over the first five
years of treatment, and each relapse carries a biological risk of
loss of function, treatment refractoriness, and changes in brain
morphology.5,6,7 Patients are often unaware of their illness and
its consequences, contributing to treatment nonadherence, high
discontinuation rates, and ultimately, significant direct and
indirect healthcare costs from subsequent relapses and
hospitalizations.2,3,4,5,6,7
About UZEDY
UZEDY (risperidone) extended-release injectable suspension, for
subcutaneous use, is indicated for the treatment of schizophrenia
in adults. In clinical trials, UZEDY significantly reduced the risk
of schizophrenia relapse.1,8 UZEDY administers risperidone through
copolymer technology under license from MedinCell that allows for
absorption and sustained release after subcutaneous injection.
UZEDY is the only long-acting, subcutaneous formulation of
risperidone available in both one- and two-month dosing intervals.8
For full prescribing information, visit
https://www.uzedy.com/globalassets/uzedy/prescribing-information.pdf.
IMPORTANT SAFETY INFORMATION CONTINUED
CONTRAINDICATIONS: UZEDY is contraindicated in patients
with a known hypersensitivity to risperidone, its metabolite,
paliperidone, or to any of its components. Hypersensitivity
reactions, including anaphylactic reactions and angioedema, have
been reported in patients treated with risperidone or
paliperidone.
WARNINGS AND PRECAUTIONS
Cerebrovascular Adverse Reactions: In trials of elderly
patients with dementia-related psychosis, there was a significantly
higher incidence of cerebrovascular adverse events (e.g., stroke,
transient ischemic attack), including fatalities, in patients
treated with oral risperidone compared to placebo. UZEDY is not
approved for use in patients with dementia-related psychosis.
Neuroleptic Malignant Syndrome (NMS): NMS, a potentially
fatal symptom complex, has been reported in association with
antipsychotic drugs. Clinical manifestations of NMS are
hyperpyrexia, muscle rigidity, altered mental status including
delirium, and 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. If NMS is
suspected, immediately discontinue UZEDY and provide symptomatic
treatment and monitoring.
Tardive Dyskinesia (TD): TD, a syndrome consisting of
potentially irreversible, involuntary, dyskinetic movements, may
develop in patients treated with antipsychotic drugs. Although the
prevalence of the syndrome appears to be highest among the elderly,
especially elderly women, it is impossible to predict which
patients will develop the syndrome. Whether antipsychotic drug
products differ in their potential to cause TD is unknown.
The risk of developing TD and the likelihood that it will become
irreversible are believed to increase with the duration of
treatment and the cumulative dose. The syndrome can develop, after
relatively brief treatment periods, even at low doses. It may also
occur after discontinuation. TD may remit, partially or completely,
if antipsychotic treatment is discontinued. Antipsychotic
treatment, itself, however, may suppress (or partially suppress)
the signs and symptoms of the syndrome, possibly masking the
underlying process. The effect that symptomatic suppression has
upon the long-term course of the syndrome is unknown.
If signs and symptoms of TD appear in a patient treated with
UZEDY, drug discontinuation should be considered. However, some
patients may require treatment with UZEDY despite the presence of
the syndrome. In patients who do require chronic treatment, use the
lowest dose and the shortest duration of treatment producing a
satisfactory clinical response. Periodically reassess the need for
continued treatment.
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 (DM), in some cases
extreme and associated with ketoacidosis or hyperosmolar coma or
death, have been reported in patients treated with atypical
antipsychotics, including risperidone. Patients with an established
diagnosis of DM who are started on atypical antipsychotics,
including UZEDY, should be monitored regularly for worsening of
glucose control. Patients with risk factors for DM (e.g., obesity,
family history of diabetes) who are starting treatment with
atypical antipsychotics, including UZEDY, should undergo fasting
blood glucose (FBG) testing at the beginning of treatment and
periodically during treatment. Any patient treated with atypical
antipsychotics, including UZEDY, should be monitored for symptoms
of hyperglycemia including polydipsia, polyuria, polyphagia, and
weakness. Patients who develop symptoms of hyperglycemia during
treatment with atypical antipsychotics, including UZEDY, should
undergo FBG testing. In some cases, hyperglycemia has resolved when
the atypical antipsychotic, including risperidone, was
discontinued; however, some patients required continuation of
antidiabetic treatment despite discontinuation of risperidone.
Dyslipidemia has been observed in patients treated with
atypical antipsychotics.
Weight gain has been observed with atypical antipsychotic
use. Monitoring weight is recommended.
Hyperprolactinemia: As with other drugs that antagonize
dopamine D2 receptors, risperidone elevates prolactin levels and
the elevation persists during chronic administration. Risperidone
is associated with higher levels of prolactin elevation than other
antipsychotic agents.
Orthostatic Hypotension and Syncope: UZEDY may induce
orthostatic hypotension associated with dizziness, tachycardia, and
in some patients, syncope. UZEDY should be used with particular
caution in patients with known cardiovascular disease,
cerebrovascular disease, and conditions which would predispose
patients to hypotension and in the elderly and patients with renal
or hepatic impairment. Monitoring of orthostatic vital signs should
be considered in all such patients, and a dose reduction should be
considered if hypotension occurs. Clinically significant
hypotension has been observed with concomitant use of oral
risperidone and antihypertensive medication.
Falls: Antipsychotics, including UZEDY, may cause
somnolence, postural hypotension, motor and sensory instability,
which may lead to falls and, consequently, fractures or other
fall-related injuries. Somnolence, postural hypotension, motor and
sensory instability have been reported with the use of risperidone.
For patients, particularly the elderly, with diseases, conditions,
or medications that could exacerbate these effects, assess the risk
of falls when initiating antipsychotic treatment and recurrently
for patients on long-term antipsychotic therapy.
Leukopenia, Neutropenia, and Agranulocytosis have been
reported with antipsychotic agents, including risperidone. In
patients with a pre-existing history of a clinically significant
low white blood cell count (WBC) or absolute neutrophil count (ANC)
or a history of drug-induced leukopenia or neutropenia, perform a
complete blood count (CBC) frequently during the first few months
of therapy. In such patients, consider discontinuation of UZEDY at
the first sign of a clinically significant decline in WBC 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 UZEDY in patients with ANC < 1000/mm3) and
follow their WBC until recovery.
Potential for Cognitive and Motor Impairment: UZEDY, like
other antipsychotics, may cause somnolence and has the potential to
impair judgement, thinking, and motor skills. Somnolence was a
commonly reported adverse reaction associated with oral risperidone
treatment. Caution patients about operating hazardous machinery,
including motor vehicles, until they are reasonably certain that
treatment with UZEDY does not affect them adversely.
Seizures: During premarketing studies of oral risperidone
in adult patients with schizophrenia, seizures occurred in 0.3% of
patients (9 out of 2,607 patients), two in association with
hyponatremia. Use UZEDY cautiously in patients with a history of
seizures or other conditions that potentially lower the seizure
threshold.
Dysphagia: Esophageal dysmotility and aspiration have
been associated with antipsychotic drug use. Antipsychotic drugs,
including UZEDY, should be used cautiously in patients at risk for
aspiration.
Priapism has been reported during postmarketing
surveillance for other risperidone products. A case of priapism was
reported in premarket studies of UZEDY. Severe priapism may require
surgical intervention.
Body temperature regulation. Disruption of the body’s
ability to reduce core body temperature has been attributed to
antipsychotic agents. Both hyperthermia and hypothermia have been
reported in association with oral risperidone use. Strenuous
exercise, exposure to extreme heat, dehydration, and
anticholinergic medications may contribute to an elevation in core
body temperature; use UZEDY with caution in patients who experience
these conditions.
ADVERSE REACTIONS
The most common adverse reactions with risperidone (≥5% and
greater than placebo) were parkinsonism, akathisia, dystonia,
tremor, sedation, dizziness, anxiety, blurred vision, nausea,
vomiting, upper abdominal pain, stomach discomfort, dyspepsia,
diarrhea, salivary hypersecretion, constipation, dry mouth,
increased appetite, increased weight, fatigue, rash, nasal
congestion, upper respiratory tract infection, nasopharyngitis, and
pharyngolaryngeal pain.
The most common injection site reactions with UZEDY (≥5% and
greater than placebo) were pruritus and nodule.
DRUG INTERACTIONS
- Carbamazepine and other strong CYP3A4 inducers decrease plasma
concentrations of risperidone.
- Fluoxetine, paroxetine, and other strong CYP2D6 inhibitors
increase risperidone plasma concentration.
- Due to additive pharmacologic effects, the concomitant use of
centrally-acting drugs, including alcohol, may increase nervous
system disorders.
- UZEDY may enhance the hypotensive effects of other therapeutic
agents with this potential.
- UZEDY may antagonize the pharmacologic effects of dopamine
agonists.
- Concomitant use with methylphenidate, when there is change in
dosage of either medication, may increase the risk of
extrapyramidal symptoms (EPS)
USE IN SPECIFIC POPULATIONS
Pregnancy: May cause EPS and/or withdrawal symptoms in
neonates with third trimester exposure. There is a pregnancy
exposure registry that monitors pregnancy outcomes in women exposed
to atypical antipsychotics, including UZEDY, during pregnancy.
Healthcare providers are encouraged to register patients by
contacting the National Pregnancy Registry for Atypical
Antipsychotics at 1-866-961-2388 or online at
http://womensmentalhealth.org/clinicaland-research-programs/pregnancyregistry/.
Lactation: Infants exposed to risperidone through
breastmilk should be monitored for excess sedation, failure to
thrive, jitteriness, and EPS.
Fertility: UZEDY may cause a reversible reduction in
fertility in females.
Pediatric Use: Safety and effectiveness of UZEDY have not
been established in pediatric patients.
Renal or Hepatic Impairment: Carefully titrate on oral
risperidone up to at least 2 mg daily before initiating treatment
with UZEDY.
Patients with Parkinson’s disease or dementia with Lewy
bodies can experience increased sensitivity to UZEDY.
Manifestations and features are consistent with NMS.
Please see the full Prescribing Information for
UZEDY, including Boxed WARNING.
About Teva
Teva Pharmaceutical Industries Ltd. (NYSE and TASE: TEVA) is a
global pharmaceutical leader with a category-defying portfolio,
harnessing our generics expertise and stepping up innovation to
continue the momentum behind the discovery, delivery, and expanded
development of modern medicine. For over 120 years, Teva’s
commitment to bettering health has never wavered. Today, the
company’s global network of capabilities enables its ~37,000
employees across 58 markets to push the boundaries of scientific
innovation and deliver quality medicines to help improve health
outcomes of millions of patients every day. To learn more about how
Teva is all in for better health, visit www.tevapharm.com.
Cautionary Note Regarding Forward-Looking Statements
This press release contains forward-looking statements within
the meaning of the Private Securities Litigation Reform Act of
1995, which are based on management’s current beliefs and
expectations and are subject to substantial risks and
uncertainties, both known and unknown, that could cause our future
results, performance or achievements to differ significantly from
that expressed or implied by such forward-looking statements. You
can identify these forward-looking statements by the use of words
such as “should,” “expect,” “anticipate,” “estimate,” “target,”
“may,” “project,” “guidance,” “intend,” “plan,” “believe” and other
words and terms of similar meaning and expression in connection
with any discussion of future operating or financial performance.
Important factors that could cause or contribute to such
differences include risks relating to: our ability to successfully
develop and commercialize UZEDY (risperidone) extended-release
injectable suspension for the treatment schizophrenia; our ability
to successfully compete in the marketplace, including our ability
to develop and commercialize additional pharmaceutical products;
our ability to successfully execute our Pivot to Growth strategy,
including to expand our innovative and biosimilar medicines
pipeline and profitably commercialize the innovative medicines and
biosimilar portfolio, whether organically or through business
development, and to sustain and focus our portfolio of generics
medicines; and other factors discussed in our Quarterly Report on
Form 10-Q for the first quarter of 2024 and in our Annual Report on
Form 10-K for the year ended December 31, 2023, including in the
section captioned “Risk Factors.” Forward-looking statements speak
only as of the date on which they are made, and we assume no
obligation to update or revise any forward-looking statements or
other information contained herein, whether as a result of new
information, future events or otherwise. You are cautioned not to
put undue reliance on these forward-looking statements.
_________________ 1 Data on file. Parsippany, NJ: Teva
Neuroscience, Inc. 2 Substance Abuse and Mental Health Services
Administration. Schizophrenia.
https://www.samhsa.gov/mental-health/schizophrenia. Accessed
November 2023. 3 Velligan DI, Rao S. The Epidemiology and Global
Burden of Schizophrenia. J Clin Psychiatry. 2023;84(1):MS21078COM5.
https://doi.org/10.4088/JCP.MS21078COM5. 4 Wander C. (2020).
Schizophrenia: Opportunities to Improve Outcomes and Reduce
Economic Burden Through Managed Care. The Am J Manag Care. 26(3
Suppl), S62–S68. https://doi.org/10.37765/ajmc.2020.43013. 5
Emsley, R., & Kilian, S. (2018). Efficacy and safety profile of
paliperidone palmitate injections in the management of patients
with schizophrenia: an evidence-based review. Neuropsychiatric Dis.
Treat., 14, 205–223. 6 Emsley, R., Chiliza, B., Asmal, L. et al.
(2013) The nature of relapse in schizophrenia. BMC Psychiatry 13,
50. 7 Andreasen, N. C., et al. (2013). Relapse duration, treatment
intensity, and brain tissue loss in schizophrenia: a prospective
longitudinal MRI study. The Am J Psychiatry, 170(6), 609–615. 8
UZEDY® (risperidone) extended-release injectable suspension, for
subcutaneous injection Current Prescribing Information. Parsippany,
NJ. Teva Neuroscience, Inc.
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PR Contacts Kelley Dougherty +1 (973) 832-2810 Eden Klein
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