Alkermes公司4月8日公布了精神分裂症药物aripiprazole lauroxil一项随机、双盲、安慰剂对照III期研究的积极数据。研究数据表明，与安慰剂组相比，每月一次aripiprazole lauroxil 441mg剂量组和882mg剂量组在第12周时的阴性症状量表（PANSS）均取得了统计学意义的显著改善，达到了该项研究的主要终点。此外，与安慰剂组相比，aripiprazole lauroxil 2个剂量组在第12周时的临床总体印象-改善量表（CGI-I）也取得了统计学意义的显著改善，达到了该项研究的关键次要终点。研究中，aripiprazole lauroxil耐受性良好，安全性与所报道的口服aripiprazole相似。根据获得的积极数据，Alkermes公司计划于2014年第三季度向FDA提交aripiprazole lauroxil的新药申请（NDA）。
aripiprazole lauroxil是一种新的长效注射型非典型抗精神病药物，旨在为患者提供每月一次的药物。该药在人体内会转变成aripiprazole，而该分子是大冢（Otsuka）抗精神分裂症重磅药物阿立哌唑（Abilify）的成分。
在美国，非典型抗精神分裂症市场价值45亿美元，该市场正在不断增长。Alkermes公司的技术能够使药物在体内受控释放，使患者减少服药频率。礼来（Eli Lilly）抗精神分裂症注射药物普乐（Zyprexa Relprew）已获批用于精神分裂症治疗，该药2-4周给药一次，取决于剂量。大冢的注射药物Abilify Maintena为每月给药一次。
目前，Alkermes也正在开发3个月注射一次的抗精神分裂症药物Invega Sustenna。
― Once-Monthly Injectable Schizophrenia Medication Achieved Primary and Secondary Endpoints at Both Doses Tested in Pivotal Study ―
― Company Plans To Submit New Drug Application in Third Quarter of 2014 ―
DUBLIN--(BUSINESS WIRE)--Apr. 8, 2014-- Alkermes plc (NASDAQ: ALKS) today announced positive topline results from a randomized, double-blind, placebo-controlled phase 3 clinical trial of aripiprazole lauroxil in patients with schizophrenia. Patients treated once monthly with either 441 mg or 882 mg of aripiprazole lauroxil demonstrated statistically significant reductions from baseline in Positive and Negative Syndrome Scale (PANSS) total scores at week 12, compared to placebo (p<0.001 aripiprazole lauroxil 441 mg, p<0.001 aripiprazole lauroxil 882 mg), which was the prespecified primary endpoint in the study. Based on the positive results from this phase 3 study, Alkermes plans to submit a New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) in the third quarter of 2014. Aripiprazole lauroxil is a new, long-acting injectable antipsychotic agent designed to provide patients with once-monthly dosing of a medication that, once in the body, converts to aripiprazole, a molecule that is commercially available under the name ABILIFY®.
“These statistically significant efficacy data demonstrate aripiprazole lauroxil’s ability to provide clinically meaningful symptom control in patients struggling with schizophrenia,” said Henry Nasrallah, M.D., Chair, Department of Neurology and Psychiatry at Saint Louis University School of Medicine. “A once-monthly version of aripiprazole with multiple dose strengths would be a welcome addition since it would enhance current treatment options and provide dosing flexibility. These data come at a time when the treatment landscape for schizophrenia is evolving; more physicians are now recognizing the benefits of long-acting injectable antipsychotics and considering their use earlier in disease progression.”
Data from the full analysis set showed statistically significant improvement in PANSS total scores from baseline in both aripiprazole lauroxil dose groups, relative to the placebo treatment group. In addition to meeting the prespecified primary efficacy endpoint, the study also met the prespecified key secondary endpoint of improvement on the Clinical Global Impression C Improvement scale (CGI-I) versus placebo at week 12 (p<0.001).
“Our goal has been to develop a differentiated long-acting injectable product candidate responsive to the real-world needs of patients and healthcare providers, providing the proven efficacy of aripiprazole administered once-monthly in a ready-to-use format with multiple dosage strengths,” stated Richard Pops, Chief Executive Officer of Alkermes. “With these positive data in hand, we will complete the preparation of our NDA, which we plan to submit next quarter, and continue our preparations to bring this imp0rtant new medicine to patients and healthcare providers.”
Aripiprazole lauroxil was generally well tolerated in the phase 3 study, and the safety profile of aripiprazole lauroxil was similar to that reported with oral aripiprazole. The most common adverse events in the study were insomnia, akathisia and headache.
Alkermes will present comprehensive data from the phase 3 study at an upcoming medical meeting and submit the results for publication in a peer-reviewed journal.
Phase 3 Study Design
The phase 3, randomized, multicenter, double-blind, placebo-controlled study was designed to assess the efficacy, safety and tolerability of aripiprazole lauroxil in patients experiencing acute exacerbation of schizophrenia. The trial included adult patients who met the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR®) criteria for schizophrenia and had a PANSS total score of 70 or higher at study baseline.
A total of 623 patients were randomized to receive once-monthly intramuscular injections of aripiprazole lauroxil 441 mg, aripiprazole lauroxil 882 mg or placebo for 12 weeks. Following randomization, patients received their first injection along with daily oral study drug for the first three weeks. Patients randomized to the two aripiprazole lauroxil treatment groups received oral aripiprazole for those initial three weeks, while patients randomized to the placebo group received matching oral placebo for three weeks. The primary efficacy endpoint of the study was the change from baseline at week 12 in PANSS total score, using an analysis of covariance (ANCOVA) with a last observation carried forward (LOCF). The key secondary endpoint was the CGI-I score at week 12.
All participants in the double-blind portion of the study are eligible to continue in an open-label phase and receive aripiprazole lauroxil for an additional 12 months. The objective of the extension phase of the study is to assess the safety and long-term durability of effect of once-monthly aripiprazole lauroxil.
ab0ut Aripiprazole Lauroxil
Aripiprazole lauroxil, which utilizes Alkermes’ proprietary 1inkeRx® technology, is an injectable atypical antipsychotic with one-month and two-month formulations in development for the treatment of schizophrenia. Once in the body, aripiprazole lauroxil converts to aripiprazole, which is commercially available under the name ABILIFY.
ab0ut Schizophrenia and Long-Acting Medicines
Schizophrenia is a chronic, severe and disabling brain disorder. The disease is marked by positive symptoms (hallucinations and delusions) and negative symptoms (depression, blunted emotions and social withdrawal), as well as by disorganized thinking. An estimated 2.4 million Americans have schizophrenia,1 with men and women affected equally. Worldwide, it is estimated that one person in every 100 develops schizophrenia, one of the most serious types of mental illness.
Long-acting injectable antipsychotics provide patients with blood concentrations of active drug that remain within a therapeutic range for an extended period of time2 and allow healthcare providers to track when a patient does not return for a scheduled injection.
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