Med Check

Regulatory Briefs

• The Food and Drug Administration (FDA) has approved generic formulations of divalproex sodium extended-release tablets (Depakote), according to a report by Reuters on July 30. The drug is approved to treat epilepsy, bipolar disorder, and migraine headache. Various generic manufacturers have received the agency's green light to produce the drug.

• The FDA has approved valproic acid delayed-release capsules (Stavzor) for marketing, according to an announcement by Noven Pharmaceuticals Inc. on July 30. Although the active ingredient is not a new molecular entity, the manufacturer's proprietary enteric soft-gel capsule formulation makes it a brand-name product and purports to protect against gastric reflux and irritability, the company's announcement asserted. The prescribing information is posted at<www.fda.gov/cder/foi/label/2008/022152lbl.pdf>.

• The FDA has issued a not-approvable letter for the new drug application of iloperidone, an antipsychotic developed by Vanda Pharmaceuticals. According to a Reuter's report on July 28, the company told analysts that the FDA had required additional data on the long-term effects of the drug and its efficacy in comparison with placebo and currently available antipsychotics such as olanzapine and risperidone. The future development of iloperidone remains unclear.

• The package insert of methylphenidate extended-release tablets (Concerta) was revised in June to incorporate changes to the sections on contraindictions, warnings and precautions, adverse reactions, and patient counseling information.

Hypersensitivity to methylphenidate is noted as a contraindication for prescribing the drug. The risk of serious cardiovascular events, including sudden death and other serious events in adults taking usual doses of stimulants for ADHD, are described. Postmarketing reports of adverse reactions have been added to the package insert as well as to the medication guide for patients.

The FDA announcement on the labeling revisions is posted at<www.fda.gov/medwatch/SAFETY/2008/jun08.htm#Concerta>.

• The FDA issued a safety warning for health care professionals and the public about the risk of serious injection-site reactions associated with naltrexone extended-release injectable suspension (Vivitrol) on August 12. Patients are advised to contact their physicians if they experience pain, swelling, tenderness, bruising, pruritus, or redness at the injection site that does not improve or worsens within two weeks. Physicians are advised to refer promptly patients with serious reactions to a surgeon. This warning was based on 196 reports of injection-site reactions so far, including cellulitus, induration, hematoma, abscess, and necrosis from patients who received this intramuscular injection.

The warning is posted at<www.fda.gov/cder/drug/InfoSheets/HCP/naltrexoneHCP.htm>.

Legal Briefs

• A bill for a federal “academic detailing” program intended to provide nonindustry medical information to physicians was introduced in the Senate on July 31 (S 3396), according to a press release by the Senate Special Committee on Aging.

If passed, the legislation will set up a system to provide physicians and other health care professionals with information on prescription drugs to counter the promotional efforts of pharmaceutical sales representatives. One of the sponsors of the bill, Sen. Herb Kohl (D-Wis.), called it “an important alternative to the way doctors currently get their information about drugs” in the press release.

Proposed actions including issuing grants to develop independent educational materials for physicians and other prescribers and sending trained health care professionals, such as pharmaceutical representatives, to doctors' offices to promote these independent materials. Reps. Henry Waxman (D-Calif.) and Frank Pallone (D-N.J.) introduced the same bill in the House of Representatives (HR 6752).

The Senate Special Committee on Aging announcement is posted at<aging.senate.gov/hearing_detail.cfm?id=301620&>.

• Massachusetts Gov. Deval Patrick (D) has signed into law a regulation that restricts pharmaceutical companies' gifts to health care professionals, according to a report in the August 11 Boston Globe. The state legislature had passed the bill, which requires pharmaceutical and medical device companies to publicly disclose gifts to health care professionals that are worth more than $50. Also, certain types of gifts, such as sports tickets and free travel, are banned. An earlier effort in the state legislature to ban all industry gifts to physicians had failed to gain full support. This legislation was proposed in an attempt to control the state's escalating health care costs since it began mandating health insurance for all residents two years ago, the report noted.

Industry and Research Briefs

• Forest Laboratories presented favorable results from a phase 3 clinical trial of once-daily memantine extended-release in treating patients with moderate to severe Alzheimer's disease at the 2008 Alzheimer's Association International Conference on Alzheimer's Disease (ICAD) in Chicago in July.

In the randomized, double-blind, placebo-controlled trial sponsored by the company, 677 patients who were taking a cholinesterase inhibitor (for example, donepezil, galantamine, or rivastigmine) were given either placebo or 28 mg/day of memantine for 24 weeks. The symptom severity, measured by change from baseline on the Severe Impairment Battery and the Clinician's Interview-Based Impression of Change Plus Caregiver Input scales, was statistically significantly better in patients taking memantine than in those taking placebo. The adverse events associated with memantine were infrequent and included dizziness, diarrhea, and headache.

• TauRx Therapeutics, a Singapore-based pharmaceutical company, presented results from a phase 2 clinical trial showing efficacy of a proprietary oral formulation of methylthionium chloride (Rember) on the cognition of patients with Alzheimer's disease at the ICAD. The active ingredient is a chemical and biological dye often used as a staining agent. The company is studying its effects as an inhibitor of the tau protein aggregation, which has been linked to Alzheimer's disease.

In the double-blind, multidose, clinical trial conducted in the United Kingdom and Singapore, 321 patients were randomized to receive either the active drug or placebo. After six months of treatment, patients taking the active drug at 60 mg three times daily had statistically significantly better cognitive scores on the subscale of the Alzheimer's Disease Assessment Scale (ADAS) than those who took placebo, according to a press release from the ICAD.

• Disappointing results from a phase 3 clinical trial of tarenflurbil (Flurizan) were presented at the ICAD. The investigational drug targets the beta-amyloid protein build-up, but the 18-month, randomized, double-blind, placebo-controlled trial in 1,649 patients with mild Alzheimer's disease failed to meet its primary efficacy endpoints as measured by the cognition and activities of daily living subscales of the ADAS. Myriad Genetics announced that it would abandon the development of this molecule.

• GlaxoSmithKline said in July that it entered into a collaborative deal with Actelion, a Swiss biopharmaceutical company, to develop and market an investigational drug, almorexant, for treatment of insomnia. Almorexant, known as an orexin receptor antagonist, is being studied in phase 3 clinical trials evaluating its safety and efficacy in adults and elderly patients with primary insomnia.

• The Pharmaceutical Research and Manufacturers of America (PhRMA) released a report on July 24 listing more than 300 new drugs under investigation by pharmaceutical companies to treat various mental illnesses. Dementia treatments lead the research categories, with 89 products being developed, followed by products for depression and anxiety disorders.

The report is posted at<www.phrma.org/files/Mental%20Illness%202008.pdf>.▪