LATUDA® (lurasidone HCl) Shown to be Non-Inferior to SEROQUEL XR® (quetiapine fumarate XR) in Risk for Relapse in a 12-Month, Double-Blind Extension Study of Adult Patients with Schizophrenia
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Results from a 12-month, double-blind extension study comparing LATUDA to SEROQUEL XR in adult patients with schizophrenia demonstrated LATUDA to be non-inferior to SEROQUEL XR in risk for relapse.
MARLBOROUGH, MA, USA I October 27, 2011 I Sunovion Pharmaceuticals Inc. today announced results from a 12-month, double-blind extension study comparing LATUDA to SEROQUEL XR in adult patients with schizophrenia. The results of the extension study demonstrated LATUDA to be non-inferior to SEROQUEL XR in risk for relapse.
The primary efficacy endpoint was time to relapse of psychotic symptoms, applying pre-specified relapse criteria. The primary analysis utilized a Cox proportional hazards model to assess non-inferiority of LATUDA compared to SEROQUEL XR. Results of this analysis showed a hazard ratio of 0.728 (indicating a 27% lower risk of relapse for LATUDA), with an upper limit of the 95% CI of 1.295. Since the protocol pre-specified margin for non-inferiority was 1.93, this study successfully demonstrated non-inferiority of LATUDA compared to SEROQUEL XR.
Adverse events (greater than or equal to 5%) associated with LATUDA included akathisia, headache, insomnia, anxiety, increased weight and parkinsonism. Adverse events associated with SEROQUEL XR (greater than or equal to 5%) included schizophrenia, headache, insomnia, psychotic disorder, increased weight and agitation. LATUDA was also associated with low rates of weight gain and metabolic changes.
About the “PEARL 3*” Extension Study
The double-blind extension study followed a core six-week, double-blind, placebo-controlled study (PEARL 3) where patients were randomized to treatment with one of the following: LATUDA 80 mg/day, LATUDA 160 mg/day, SEROQUEL XR 600 mg/day or placebo. A total of 292 patients entered the extension study.
Patients treated with LATUDA 80 mg/day or 160 mg/day in the preceding PEARL 3 study were treated with a fixed dose of LATUDA 120 mg/day for the first week of the extension study, and were then flexibly dosed (LATUDA 40 mg/day – 160 mg/day), at the investigator's discretion, for up to 52 weeks (N=151).
Patients treated with SEROQUEL XR 600 mg/day in the preceding PEARL 3 study were treated with SEROQUEL XR 600 mg/day for the first week of the extension study, and were then flexibly dosed (SEROQUEL XR 200 mg/day – 800 mg/day) for up to 52 weeks (N=85).
Patients on placebo in the PEARL 3 study (N=56) were transitioned to LATUDA in the extension study in a manner similar to those patients who had been taking LATUDA (results of the primary and secondary analyses discussed below do not include PEARL 3 study placebo patients who entered the extension study).
The mean age was 37.1 years for the LATUDA treatment group and 38.5 years for the SEROQUEL XR group. The gender distribution was 72% male for the LATUDA group and 61% male for the SEROQUEL XR group.
Other key findings for this 12-month, double-blind extension study are as follows:
Probability of Relapse:1 The probability of relapse at month 12 (based on Kaplan-Meier survival analysis) was 23.7% for LATUDA and 33.6% for SEROQUEL XR.
Discontinuation due to treatment failure (insufficient clinical response or adverse events): Rates were 16% for LATUDA and 26% for SEROQUEL XR.
Additional findings from the acute baseline (start of the PEARL 3 study) to the 12-month extension study endpoint are outlined below.2
PANSS Total Scores: LS mean changes were: -34.6 for LATUDA and -25.7 for SEROQUEL XR (p=0.006).
Weight: Mean changes were +0.7 kg (1.5 lbs) for LATUDA and +1.2 kg (2.6 lbs) for SEROQUEL XR.
Cholesterol: Median changes were 0.0 mg/dL increase for LATUDA and +4.0 mg/dL increase for SEROQUEL XR.
Triglycerides: Median changes were -18.0 mg/dL for LATUDA and -7.0 mg/dL for SEROQUEL XR.
Glucose: Median changes were +1.0 mg/dL for both LATUDA and SEROQUEL XR.
1 The pre-specified relapse population definition included all patients who demonstrated clinical response to six weeks of treatment with either LATUDA or SEROQUEL XR and received at least one dose of study medication in the extension study.
2 Weight and laboratory measure data were obtained from 12-month observed case analysis.
"This study presents an important opportunity to understand how LATUDA compares to another widely used atypical agent, SEROQUEL XR. Long-term, double-blind data such as those provided in this year-long study are essential to aid physicians in choosing the best medication for their patients, balancing efficacy and side effects. More of such studies are needed and would improve patient care," said Steven G. Potkin, M.D., professor, Department of Psychiatry and Human Behavior, University of California, Irvine. "In this study, the group of patients who took LATUDA experienced fewer relapses and lower rates of weight gain and other metabolic concerns than those taking SEROQUEL XR."
“Physicians and payers are increasingly interested in results from comparative assessments of active agents, so that use of scarce resources can be optimized. We conducted this double-blind study to evaluate relapse risk over a 12-month period for LATUDA and SEROQUEL XR in patients with schizophrenia, as relapse is a key driver of both costs and clinical outcome. We are pleased to see that the study successfully showed LATUDA to be non-inferior to SEROQUEL XR in terms of risk of relapse and to have a lower discontinuation rate due to treatment failure,” said Antony Loebel, M.D., executive vice president, Clinical Development and Medical Affairs at Sunovion Pharmaceuticals Inc.
LATUDA received U.S. Food and Drug Administration (FDA) approval for the treatment of schizophrenia on October 28, 2010 and is available in pharmacies across the U.S. and Puerto Rico. A supplemental New Drug Application for a 160 mg/day dose of LATUDA is under review at the FDA but has not been approved for use.
The full study findings will be presented at a future psychiatric medical congress. The press release announcing results from the core study (PEARL 3) can be viewed at: http://www.sunovion.com/news/pressReleases/20101208.pdf.
LATUDA is an atypical antipsychotic indicated for the treatment of patients with schizophrenia. Efficacy was established in four 6-week controlled studies of adult patients with schizophrenia. The effectiveness of LATUDA for longer-term use, that is, for more than 6 weeks, has not been established in controlled studies. Therefore, the physician who elects to use LATUDA for extended periods should periodically re-evaluate the long-term usefulness of the drug for the individual patient.
The recommended starting dose for LATUDA is 40mg/day taken with food (at least 350 calories) with no initial dose titration required. LATUDA has been shown to be effective in dose ranges of 40 mg/day to 120 mg/day. In the 6-week controlled trials, there was no suggestion of added benefit with the 120 mg/day dose, but there was a dose-related increase in certain adverse reactions. Therefore, the maximum recommended dose is 80 mg/day. For patients with moderate to severe renal or hepatic impairment, the dose of LATUDA should not exceed 40 mg/day. LATUDA should not be administered with strong CYP3A4 inhibitors such as ketoconazole or strong CYP3A4 inducers such as rifampin.
Schizophrenia is a chronic, disabling and serious brain disorder that affects approximately 2.4 million American adults or 1 in 100 people. Schizophrenia is characterized by symptoms such as hallucinations, delusions, disorganized thinking, lack of emotion, lack of energy, as well as problems with memory, attention and the ability to plan, organize and make decisions.
About Sunovion Pharmaceuticals Inc. (Sunovion)
Sunovion is a leading pharmaceutical company dedicated to discovering, developing and commercializing therapeutic products that advance the science of medicine in the central nervous system (CNS) and respiratory disease areas and improve the lives of patients and their families. Sunovion’s drug development program, together with its corporate development and licensing efforts, has yielded a portfolio of pharmaceutical products including LATUDA® brand lurasidone HCl, LUNESTA® brand eszopiclone, XOPENEX® brand levalbuterol HCl Inhalation Solution, XOPENEX HFA® brand levalbuterol tartrate inhalation aerosol, BROVANA® brand aformoterol tartrate inhalation solution, OMNARIS® brand ciclesonide nasal spray and ALVESCO® brand ciclesonide HFA inhalation aerosol.
Sunovion, an indirect, wholly-owned subsidiary of Dainippon Sumitomo Pharma Co., Ltd., is headquartered in Marlborough, Mass. More information about Sunovion Pharmaceuticals Inc. is available at www.sunovion.com.
About Dainippon Sumitomo Pharma Co., Ltd. (DSP)
DSP is a multi-billion dollar, top-ten listed pharmaceutical company in Japan with a diverse portfolio of pharmaceutical, animal health and food and specialty products. DSP aims to produce innovative pharmaceutical products in the CNS field, which has been designated as the key therapeutic area and will also focus in on other specialty disease categories with significant unmet medical needs, which are designated as frontier therapeutic areas. DSP is based on the merger in 2005 between Dainippon Pharmaceutical Co., Ltd., and Sumitomo Pharmaceuticals Co., Ltd. Today, DSP has more than 7,000 employees worldwide. Additional information about DSP is available through its corporate website at www.ds-pharma.com.
SOURCE: Sunovion Pharmaceuticals