Med Check

A phase 2b study of an investigational antidepressant, TC-5214, yielded positive results, the drug maker Targacept Inc. said on October 15. TC-5214 is a neuronal nicotinic receptor modulator, and its antidepressant effect is believed to be a result of reducing the overstimulation of acetylcholine-activated neurons in the brain. In the recently completed clinical trial, TC-5214 as an add-on treatment to citalopram was shown to be statistically significantly more effective than placebo plus citalopram in reducing the symptoms of major depressive disorder, measured by the Hamilton Rating Scale for Depression (HAM-D) and Montgomery-Asberg Depression Rating Scale (MADRS). The study included patients with major depressive disorder who had failed to achieve at least a 50 percent improvement on their MADRS score after eight weeks of citalopram treatment.

After eight weeks of double-blind combination treatment (TC-5214 or placebo added to citalopram), patients in the active-treatment group saw a 13.75 point reduction in HAM-D score compared with a 7.75 point reduction in the placebo group (p<0.0001).

Favorable results from a phase 2a, randomized, placebo-controlled study in patients with major depressive disorder were shown for clavulanic acid, an investigational antidepressant being developed by Rexahn Pharmaceuticals. In an October 19 announcement, the company said that the patients assigned to the treatment had “clinically meaningful improvement” in depressive symptoms and that response to treatment was shown within two weeks of initiating treatment. Clavulanic acid is referred to as a dual serotonin and dopamine enhancer and is being explored for treating other disorders such as Parkinson's disease, anxiety disorder, and Alzheimer's disease.

Alkermes Inc. announced positive results on October 13 from two phase 1 clinical trials of ALKS 33, an investigational drug. ALKS 33 is an opioid receptor modulator being developed to treat opioid addiction and other disorders related to opioid receptor pathways. In the two studies, healthy volunteers without opioid dependence were given ramifentanil, an opioid receptor agonist, followed by either ALKS 33 or placebo. ALKS 33 was shown to rapidly and completely block the action of ramifentanil at the tested dose. The company said it plans to move the drug into phase 2 development by the end of 2009.

An investigational drug to treat obesity that combines bupropion and naltrexone has shown cardiometabolic benefits in two clinical trials. The drug, known as Contrave, is a sustained-release formulation of the two active ingredients and is being studied by Orexigen Therapeutics in phase 3 development to treat obesity. According to data released October 24 at the annual meeting of the Obesity Society, one-third to nearly one-half of patients lost at least 10 percent of their baseline body weight after receiving the drug for 56 weeks. Study participants with type 2 diabetes saw a 1.1 percent reduction in their mean hemoglobin HA1c level from baseline. The drug beat placebo on several cardiometabolic indicators, including waist circumference and fasting triglyceride level. The company said it plans to submit a new drug application to the Food and Drug Administration (FDA) in the first half of 2010.

Positive results from a clinical trial of an antipsychotic being developed by Forest Laboratories and the Hungarian firm Gedeon Richter Plc were announced on October 28. The investigational drug, cariprazine, is a partial agonist of dopamine D₃/D₂ receptors currently in phase 2 development. In this phase 2b trial conducted in patients with schizophrenia, patients treated with cariprazine showed statistically significant improvement in Positive and Negative Syndrome Scale scores compared with patients treated with placebo. The drug is also being tested in phase 2 trials as a treatment for bipolar disorder and as an adjunctive treatment for major depressive disorder.

A Philadelphia jury ordered GlaxoSmithKline (GSK) to pay $2.5 million to a plaintiff who charged that the company's antidepressant paroxetine caused severe heart defects in her son, according to a report in the Philadelphia Inquirer on October 14. The plaintiff had claimed that taking the antidepressant during pregnancy was the cause of her son's severe heart defects and that GSK had withheld information about the risks of prenatal exposure to the drug from regulators and the public. The verdict was the first among hundreds of pending cases filed against the company over the adverse effects of paroxetine. GSK said it disagreed with the verdict and planned to appeal.

Legislation aimed at prohibiting a common tactic for keeping generic drugs off the market passed the U.S. Senate Judiciary Committee on October 15. The Preserve Access to Affordable Generics Act (S 369) was sponsored by Sen. Charles Grassley (R-Iowa) and Sen. Herb Kohl (D-Wis.) and was approved 12-7 by the committee. Manufacturers of brand-name drugs have been criticized for paying generic-drug manufacturers to delay the marketing of the generic versions for several years after patent expiration and thus prolonging the brand-name drug's market exclusivity. In 2005, two federal appellate courts ruled that the practice is legal.

The FDA approved a new dose, 30 mg, of dexmethylphenidate hydrochloride extended-release capsules for the treatment of attention-deficit/hyperactivity disorder (ADHD) in pediatric patients, according to a November 2 announcement by Novartis Pharmaceuticals. This approval was based on a clinical trial conducted in ADHD patients aged 6 to 12 in which the 30 mg dose was associated with greater symptom improvement than the 20 mg dose. The previous highest dosage approved for pediatric patients was 20 mg.

On November 4, the FDA announced a new program known as the “Safe Use Initiative” to reduce preventable harm from medication use. The agency plans to work with physicians, health care professionals, and consumers to identify drugs and drug classes that are at the most risk for medication misuse, errors, or other types of preventable problems and to develop regulatory interventions to reduce or prevent these problems. The agency will hold a series of public meetings to collect feedback on the program. More information about the initiative is posted at <www.fda.gov/Drugs/DrugSafety/ucm187806.htm>.