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"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
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.
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.
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
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.
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
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
WARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED
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.
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:
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.
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
*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
INVEGA SUSTENNA® is a registered trademark of Johnson & Johnson.
2 Saba DK, Levit KR,
3 Schizophrenia and Related Disorders Alliance of America, https://sardaa.org/resources/about-schizophrenia/ accessed on
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.
6 Lehman, A., Lieberman, J., et al. Practice Guideline for the Treatment of Patients with Schizophrenia; Second Edition.
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
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