Med Check

Regulatory Briefs

• Orexigen Therapeutics met with the Food and Drug Administration (FDA) recently regarding Contrave, an investigational combination therapy of naltrexone and bupropion for the treatment of obesity and maintenance of weight loss. Although Orexigen has already evaluated Contrave in more than 4,500 patients, the FDA asked for a trial of between 60,000 and 100,000 patients that demonstrates that the drug doesn't raise heart attack or stroke risk. In light of the FDA's request, Orexigen said it has decided not to pursue approval in the United States but it may do so in other countries.

• On May 27, the FDA's Division of Drug Marketing, Advertising, and Communications (DDMAC) posted a letter on its Web site that it sent to Noven Pharmaceuticals about a flash card for the SSRI antidepressant Pexeva (paroxetine). The letter states that the flash card "is false or misleading because it broadens the FDA-approved indication for the drug, presents unsubstantiated effectiveness claims, overstates the efficacy, and omits and minimizes important risk information associated with Pexeva."

  Promotional materials are misleading if they contain representations or suggestions that a drug is better or more effective than has been demonstrated by substantial evidence or substantial clinical experience.

  The DDMAC requested that Noven immediately cease dissemination of its promotional materials for Pexeva and submit a written response to the letter by June 7, stating its intention to comply with the request, listing all promotional materials for Pexeva that contained violations, and detailing a plan for discontinuing use of such violative materials.

  The letter is posted at < www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/EnforcementActivitiesbyFDA/WarningLettersandNoticeofViolationLetterstoPharmaceuticalCompanies/UCM256863.pdf>.

• On June 16, the FDA made a safety announcement notifying the public that the smoking cessation aid Chantix (varenicline) may be associated with a small increased risk of cardiovascular adverse events in patients who have preexisting cardiovascular disease. This safety information will be added to the "Warnings and Precautions" section of the Chantix physician labeling. The patient medication guide will also be revised to inform patients about this possible risk.

  The FDA reviewed a randomized clinical trial of 700 smokers with cardiovascular disease who were treated with Chantix or placebo. In this trial, Chantix was effective in helping patients quit smoking and remain abstinent from smoking for as long as one year. Cardiovascular adverse events were infrequent overall; however, certain events, including heart attack, were reported more frequently in patients treated with Chantix than in patients on placebo.

  The FDA said it is continuing to evaluate the cardiovascular safety of Chantix and is requiring the manufacturer to conduct a large, meta-analysis of randomized, placebo-controlled trials.

  The FDA's Chantix announcement is posted at <www.fda.gov/Drugs/DrugSafety/ucm259161.htm>.

• The FDA has notified health care professionals and the public of medication-error reports in which patients were given the antipsychotic medication risperidone (Risperdal) instead of ropinirole (Requip), a dopamine agonist used to treat Parkinson's disease and restless legs syndrome, and vice versa. In some cases, patients who took the wrong medication required hospitalization. The FDA determined that the factors contributing to the confusion between the two products include similarities of both the proprietary and generic names, similarities of the container labels and carton packaging, illegible handwriting on prescriptions, and overlapping product characteristics, such as drug strengths, dosage forms, and dosing intervals. The FDA reminded health care professionals to clearly print or spell out the medication name on prescriptions and make certain their patients know the name of their prescribed medication and the reason for taking it.

Industry Briefs

• In Hamburg, Germany, Evotec and Roche decided voluntarily to terminate the first proof-of-concept study in treatment-resistant depression with their NR2B subtype selective NMDA antagonist, EVT 101. The decision was reportedly triggered by difficulties in recruiting patients under the current study protocol, resulting in the possibility of inconclusive results.

  Evotec retains all rights in the EVT100 series, especially the back-up compound EVT103, and plans to enter into discussions for these assets in another clinical development partnership.

• Lundbeck announced on June 16 that it has completed a second six-month efficacy study in the overall clinical phase 3 trial of nalmefene for patients with alcohol dependence. In this multicenter, double-blind, placebo-controlled study, 718 individuals were randomized to receive oral administration of 20 mg of nalmefene or placebo on an as-needed basis for a total of 28 weeks of treatment. Nalmefene is the first medicine aimed at regulatory approval in Europe for the reduction of alcohol consumption in patients with alcohol dependence. Nalmefene is a selective opioid receptor ligand with antagonist activity at mu and delta opioid receptors and partial agonistic activity at the kappa opioid receptor.

  During the clinical trial, multiple primary and secondary endpoints were assessed, including number of heavy-drinking days per month, total alcohol consumption in grams per day, proportion of responders based on drinking measures, alcohol-dependence symptoms and clinical status, liver function and other laboratory tests, and treatment discontinuation effects. According to Lundbeck, all assessments were consistently in favor of nalmefene compared with placebo, although some were not statistically significant at every time point. It was consistently observed that the medical intervention with nalmefene had a strong effect that was seen within the first month and led to a reduction in alcohol consumption of over 50 percent, which was maintained throughout the study periods.

  Lundbeck plans to submit a European Marketing Authorization Application for nalmefene as a treatment for alcohol dependence toward the end of 2011.

Legal Brief

• AstraZeneca has filed suit for patent infringement against Intellipharmaceutics in U.S. District Court for the District of New Jersey relating to Intellipharmaceutics' FDA application for approval of a generic version of Seroquel XR (quetiapine fumarate extended-release) tablets. Quetiapine fumarate is an oral psychotropic agent indicated for treatment of schizophrenia, bipolar disorder, and major depressive disorder. According to Wolters Kluwer Health, sales of Seroquel XR were approximately $800 million in 2010. Intellipharmaceutics has said that it intends to vigorously defend against the complaint.