Alkermes Announces Positive Topline Results From Innovative Study of ARISTADA and INVEGA SUSTENNA for the Treatment of Schizophrenia
DUBLIN, (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
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:
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
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. ARISTADA INITIO and ARISTADA are not approved for the treatment of patients with dementia-related psychosis.? |
- 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.
Please see full Prescribing Information, including Boxed Warning for?ARISTADA INITIO?and?ARISTADA. |