Med Check

Regulatory Briefs

• In January, the European Commission approved Invega (paliperidone ER) for treatment of psychotic or manic symptoms of schizoaffective disorder. The decision follows a positive recommendation by the Committee for Medicinal Products for Human Use, the scientific committee of the European Medicines Agency. The approval is based on two international, randomized, double-blind, placebo-controlled six-week studies. Efficacy was evaluated by the change in patients' symptoms after six weeks as measured by the Positive and Negative Syndrome Scale (PANSS). Invega was superior to placebo in both studies.

• The U.S. Food and Drug Administration (FDA) in January approved Abstral (fentanyl) transmucosal tablets to manage breakthrough pain in patients with cancer aged 18 and older who already use opioid pain medication around the clock and who need and are able to safely use high doses of an additional opioid medicine. Consumers and health care professionals are encouraged to report adverse side effects or medication errors related to the use of Abstral to the FDA's MedWatch Adverse Event Reporting program at <www.fda.gov/MedWatch> or by calling (800) 332-1088.

• Roxane Laboratories and the FDA notified health care professionals of serious adverse events and deaths resulting from accidental overdose of morphine sulfate oral solutions, especially when using the high-potency 100 mg/5mL product. In most of these cases, morphine sulfate oral solutions ordered in milligrams (mg) were mistakenly interchanged for milliliters (mL) of the product. The newly approved product labeling and packaging feature revisions intended to reduce the risk of medication errors. A warning stating "ONLY FOR USE IN PATIENTS WHO ARE OPIOID TOLERANT" is displayed in a box to highlight that the morphine sulfate oral solution 100 mg per 5 mL (20 mg/mL) is indicated for use in opioid-tolerant patients only. The designation is to help differentiate this product from the 20 mg/5 mL morphine sulfate product. The MedWatch safety alert and links to the Dear Healthcare Professional Letter and product prescribing information are posted at <www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm239559.htm>.

Industry Briefs

• Mithridion Inc., a clinical-stage drug-development company focusing on central nervous system disorders, including Alzheimer's disease, announced in January that it has secured commitments of $1.25 million in new funding. The company's lead drug, which it calls MCD-386CR, is a clinical-stage drug candidate for improving memory and cognition in Alzheimer's and schizophrenia and for disease-modifying effects in Alzheimer's.

• BiolineRX Ltd. announced in January that Royalty Pharma, the new parent company of Cypress Bioscience Inc., is committed to developing Cypress's pipeline assets, which include BioLineRx's BL-1020 (CYP-1020) compound, a novel therapeutic agent for schizophrenia. In June 2010, BioLineRx and Cypress signed an exclusive licensing agreement for BL-1020 covering the United States, Canada, and Mexico.

Research Briefs

• In February, Dainippon Sumitomo Pharma Co. announced that it completed a double-blind, long-term safety and tolerability study of Latuda (lurasidone HCl) tablets for the treatment of patients with schizophrenia or schizoaffective disorder. In the 12-month study, once-daily Latuda was found to be well-tolerated and consistent with previous evaluations of its safety and tolerability. This trial compared the drug at once-daily doses of 40 mg, 80 mg, or 120 mg with risperidone at 2 mg, 4 mg, or 6 mg, in clinically stable outpatients with schizophrenia or schizoaffective disorder.

• In February AstraZeneca and Targacept Inc. announced initiation of a Phase 2b clinical trial of TC-5214, a nicotinic channel blocker, as a "switch" monotherapy treatment for patients with major depressive disorder (MDD) who do not respond adequately to initial antidepressant therapy. The companies are co-developing TC-5214. In the study, patients with MDD who do not respond adequately, based on predefined criteria, to initial open-label treatment with one of six commonly used SSRI or SNRI antidepressants are switched to receive either one of two fixed doses of TC-5214, the active control duloxetine, or placebo. Dosing in this double-blind phase of the study is twice daily for eight weeks. The primary outcome measure for the study is change from double-blind baseline at the end of the dosing period for TC-5214 on the Montgomery-Asberg Depression Rating Scale (MADRS) as compared with placebo. The study is projected to enroll approximately 350 patients in the double-blind phase from 75 centers worldwide.

• Concert Pharmaceuticals Inc. announced in February that it has entered into a Cooperative Research and Development Agreement with the Walter Reed Army Institute of Research to conduct preclinical testing on a novel compound derived from Concert's DCE (deuterated chemical entity) for seizure protection in cases of traumatic brain injury. This agreement will advance Concert's research program for drug compounds that have demonstrated antiseizure activity in preclinical models and may be effective in the treatment of epileptic or seizure-generating diseases and injuries, such as ischemic stroke and traumatic brain injury.

• Biotie's partner, H. Lundbeck, announced in January that it has completed two Phase 3 clinical trials evaluating nalmefene for the treatment of alcohol dependence. ESENSE1, a 24-week efficacy study, and SENSE, a 52-week safety study, investigated efficacy and safety of 20 mg nalmefene taken "as needed" versus placebo in patients with alcohol dependence. Biotie previously conducted three Phase 2 studies and two Phase 3 studies in alcohol dependence. The largest of the previous Phase 3 trials, conducted in 400 patients with alcohol dependence, demonstrated that nalmefene significantly reduced the average alcohol intake per patient and the number of heavy drinking days (classified as intake above five standard drinks of alcohol). Nalmefene is a small molecule opioid receptor antagonist that inhibits the reward pathway in the brain that reinforces the desire and craving for alcohol and other addictive substances.

• Shire announced in January results from a study of Vyvanse (lisdexamfetamine dimesylate), assessing its effect in a model for excessive daytime sleepiness. Vyvanse is approved in the United States, Canada, and Brazil for the treatment of attention-deficit/hyperactivity disorder. In this investigational, single-dose, single-site, randomized, placebo- and active-control study, 135 subjects received either Vyvanse at 20 mg, 50 mg, or 70 mg, placebo, or the active comparator (armodafinil 250 mg.) All groups showed improved objective wakefulness compared with the placebo group. Additional analyses showed that Vyvanse 70 mg demonstrated statistically significant improvement in objective wakefulness compared with armodafinil.

• Forest Laboratories Inc. said in January that levomilnacipran, a drug developed by the company for depression, failed in a late-stage clinical trial. Forest and its partner, French drugmaker Pierre Fabre Medicament, said the patients treated with levomilnacipran and patients treated with placebo had similar results, and the difference between them was not statistically significant. In the trial, 362 patients were given 40 mg to 100 mg of levomilnacipran daily or a placebo. The 11-week study compared the change in patients' symptoms on a clinical rating scale. Forest and Pierre Fabre are running two other late-stage trials of the drug, and they expect results from those studies in the second half of 2011.