Med Check

Industry Briefs

• In a phase 3 trial involving schizophrenia patients with predominant, persistent negative symptoms, one-year treatment with the antipsychotic medication asenapine produced a statistically significantly larger reduction in negative symptoms than did olanzapine, Schering-Plough announced on July 24. Negative symptoms were measured by the total score on the 16-item Negative Symptom Assessment scale (NSA-16). A total of 468 patients were first randomized to either olanzapine or asenapine in a 26-week, double-blind study, and 195 of them continued for another 26 weeks of an extension study. The extension study was also double-blind. At the end of the first 26 weeks, the negative symptom reduction did not differ significantly between the two groups. After one year, however, the patients who participated in the extension study had 15.8 point and 11.0 point reductions from baseline, respectively, for the asenapine and olanzapine groups on the NSA-16 score. More information about asepanine appears in Original article: Asenapine Adds to Arsenal to Treat Psychotic Disorders.

• A phase 2 trial of an investigational antidepressant yielded positive results, according to H. Lundbeck A/S, a Denmark-based pharmaceutical company, in a July 2 announcement. The drug, known as Lu AA24530, has been shown to modulate a number of serotonin receptors and, in animal studies, increase acetylcholine, norepinephrine, dopamine, and serotonin levels in certain brain regions. In the double-blind, phase 2 trial, placebo and duloxetine (as an active control) were compared with three dosage levels of Lu AA24530 for efficacy and safety in 652 patients with major depression during six weeks of treatment. The drug beat placebo and met the primary and secondary efficacy endpoints for depression symptoms, measured by standard scales, and had tolerability similar to that for duloxetine, the company said. Lu AA24530 is being developed by Lundbeck and Takeda Pharmaceuticals for treatment of depression and anxiety disorders.

• An investigational drug being developed by Sepracor Inc. for treating major depressive disorder failed to meet its primary efficacy endpoint, the company announced on July 1. The drug SEP-225289 was tested in a phase 2, double-blind study of 514 patients for eight weeks and compared with placebo and venlafaxine extended-release. The company said the findings were inconclusive, because the study drug's serum concentrations were unexpectedly low, which could indicate that patients did not get enough active drug. Pharmacologically, SEP-225289 inhibits serotonin, norepinephrine, and dopamine reuptake transporters. The company has not announced whether it will proceed with the drug's development.

• Targacept Inc. released some results of a phase 2b trial of its investigational drug TC-5214, which was tested as an augmentation treatment for major depression. In the trial, 579 patients with major depression were first given citalopram for eight weeks. The 265 patients who were nonresponders at the end of eight weeks were then randomized to receive an add-on treatment of either TC-5214 or placebo along with citalopram for another eight weeks in a double-blind phase. The group receiving TC-5214 and citalopram had significantly greater improvement in the primary endpoint, reduction of the score on the 17-item Hamilton Rating Scale for Depression, than did the group receiving citalopram and placebo. The groups also differed significantly in the secondary efficacy endpoints that measured depressive and cognitive symptoms. The trial drug is an antagonist of neuronal nicotinic receptors (NNRs) and modulates the alpha4beta2 NNR subtype. One patient in the citalopram/TC-5214 group had a seizure that was deemed to be related to the study treatment.

Regulatory Briefs

• The National Institute for Health and Clinical Excellence (NICE) announced in June that it would not change its guidelines on the use of donepezil, galantamine, rivastigmine, and memantine. NICE is an independent organization that advises the National Health Service of England, and its therapeutic guidelines are adopted by many other countries' governments to set reimbursement criteria. NICE guidelines, originally issued in 2006, recommended that donepezil, galantamine, rivastigmine, and memantine be used in treating moderate Alzheimer's disease only.

Japan-based Eisai and U.S.-based Pfizer, which comarket donepezil, fought NICE in court in the United Kingdom over its recommendation that donepezil should be used for treating moderate Alzheimer's disease only, arguing that the drug is also effective in treating mild Alzheimer's disease and that NICE's pharmacoeconomic model was flawed. The court then ruled that NICE should have made the economic model used in the decision making available for the manufacturers to review and voice their objections. After the economic model was reviewed and commented on by the manufacturers, NICE concluded that“ although a number of technical inaccuracies were highlighted, and amendments were made to the economic model, these were not sufficient to change the original conclusion that these treatments are not cost-effective in the mild stages of the disease.” In an announcement released on July 1, the companies repeated their criticism of NICE's economic model but said they would not appeal the institute's decision.

• In June, the FDA requested a safety-related labeling change for atomoxetine, a nonstimulant treatment for attention-deficit/hyperactivity disorder (ADHD). The “Warnings and Precautions” section of the drug label was expanded to include reported cases of severe liver injury that occurred mostly within 120 days of starting atomoxetine. A warning about orthostatic hypotension and syncope was also added. Details about the labeling changes are posted at<www.fda.gov/Safety/MedWatch/SafetyInformation/ucm169981.htm>.

• At its July meeting, the European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) issued an opinion against an application for marketing milnacipran as a treatment for fibromyalgia. Milnacipran is a selective serotonin and norepinephrine reuptake inhibitor. The committee reviewers decided that the efficacy of milnacipran in short-term clinical trials in fibromyalgia was marginal and were concerned that long-term data in a European population were lacking. Milnacipran is approved in the United States to treat fibromyalgia.

• The CHMP turned down a previous appeal by Pfizer at the July meeting and again refused to approve pregabalin for treatment of fibromyalgia. The committee initially issued a negative opinion in April in response to the company's application. Pregabalin has already been authorized for the treatment of neuropathic pain, partial seizures, and generalized anxiety disorder in Europe. In the United States the drug is approved for fibromyalgia, neuropathic pain associated with diabetic peripheral neuropathy, postherpetic neuralgia, and partial seizures. The CHMP cited its concerns that the drug's benefits in clinical trials had not been shown consistently in either the short term or long term.

Research Brief

The National Institute of Mental Health announced on July 21 that it would fund a large research project to investigate early and aggressive treatment for schizophrenia. The project, named the Recovery After an Initial Schizophrenia Episode (RAISE) study, will compare different interventions such as medication therapies and psychosocial treatment immediately after first-episode schizophrenia is diagnosed. These treatments will be tested in real-world clinical settings for their effectiveness in reducing symptoms, preserving cognitive function, and preventing disability.

Two research groups have been selected to lead the project: the Research Foundation for Mental Hygiene in New York City, led by Jeffrey Lieberman, M.D.; and Zucker Hillside Hospital at Feinstein Institute for Medical Research in Manhasset, N.Y., led by John Kane, M.D. Lieberman is the chair of APA's Council on Research and Quality Care, chair of the Department of Psychiatry at Columbia University College of Physicians and Surgeons, and director of the New York State Psychiatric Institute. Kane is chair of the Department of Psychiatry at Zucker Hillside Hospital and a professor of both psychiatry and neurology at Albert Einstein College of Medicine. The research will be conducted at multiple clinical sites across the United States. ▪