• In a recent settlement, Eli Lilly and Co. agreed to pay the state of Connecticut $25 million for claims that it illegally marketed its antipsychotic drug Zyprexa (olanzapine) for off-label use, according to a state attorney general's announcement on September 29. The company was accused of promoting the drug for treating dementia, depression, and attention-deficit/hyper-activity disorder (ADHD) in children and other unapproved indications as well as concealing serious side effects of the drug from the public.
The American College of Physicians (ACP) issued a policy paper on September 24 calling for broader authority for the Food and Drug Administration (FDA) to tighten medication-related regulations. In particular, the ACP wants the FDA to be given the authority to restrict direct-to-consumer advertising of new drugs during their first two years on the market. Additional ACP recommendations included increasing FDA regulation of drugs manufactured abroad and improving the current system for adverse-event reporting. The organization also called for more funding for the agency.
The ACP paper is posted at <www.acponline.org/advocacy/where_we_stand/policy/fda.pdf>.
Sanofi-Aventis said on September 16 that it received a Complete Response Letter from the FDA regarding its new drug application for eplivanserin, a serotonin 5HT2A receptor antagonist being developed for sleep maintenance in patients with chronic insomnia. The agency requested additional risk-benefit information about the medication, but the company did not indicate whether it would conduct more clinical trials.
GlaxoSmithKline announced on September 21 that it would stop making political contributions and stop funding for-profit medical education and communication companies to produce continuing medical education (CME) programs. It becomes the second large pharmaceutical company, after Pfizer, to cease distributing CME grants to commercial providers as industry-funded CME has come under increasing scrutiny and criticism for serving as a promotional activity for the drug companies' products. However, the company said it would continue to fund CME activities produced by academic medical centers and "national-level professional medical associations."
Following the approval of guanfacine for the treatment of ADHD, another alpha-2 adrenergic agonist, clonidine, is now awaiting FDA review for the same indication. A supplemental new drug application was recently submitted by Addrenex seeking the indication for an extended-release formulation of this long-prescribed antihypertensive drug, according to an October 1 company announcement. The medication has been shown to be more effective than placebo in treating ADHD in a randomized, placebo-controlled, phase 3 clinical trial.
The National Institute on Drug Abuse announced on September 30 that it awarded a $10 million grant to Nabi Biopharmaceuticals to continue its development of a nicotine vaccine for use in smoking cessation. The funding has been designated to support the first phase 3 clinical trial of the vaccine.
The vaccine, given by multiple injections, is designed to induce the body to produce an antinicotine antibody, which binds to absorbed nicotine in the blood-stream and prevents it from entering the brain and producing its neurological effect. Thus, smokers do not derive the expected sensation from smoking, making it easier for them to reduce or stop smoking and prevent relapse.
An investigational drug with a novel mechanism of action showed promise in improving the cognitive function of schizophrenia patients, according to the results from a phase 2b clinical trial released on September 23 by BioLineRx, an Israel-based company currently developing the drug known as BL-1020. It is an antipsychotic with activities affecting gamma-aminobutyric acid (GABA) and dopaminergic receptors. In the six-week, phase 2b trial, patients randomized to receive BL-1020 had a statistically significantly larger improvement of cognitive function from baseline, measured by the Brief Assessment of Cognition in Schizophrenia score, than did patients in either a group receiving placebo or one receiving risperidone.
On September 30, Catalyst Pharmaceutical Partners Inc. announced plans to continue development of its investigational drug CPP-109 for the treatment of cocaine and methamphetamine addiction. The decision was based on post-hoc analyses of results from two clinical trials in cocaine and methamphetamine addiction treatment. The trials failed to meet statistical significance in efficacy endpoints in comparisons between the drug and placebo, which the company said was largely due to the low rate of patient compliance. CPP-109 is a proprietary formulation of vigabatrin, an antiseizure medication.
Data presented at the 2009 European College of Neuropsychopharmacology (ECNP) Congress on September 14 showed that asenapine surpassed placebo in preventing relapse over six months in stabilized schizophrenia patients. A total of 700 patients were first given asenapine for 26 weeks of open-label treatment. At the end of the open-label phase, 386 of the patients were randomly assigned to an additional 26 weeks of a double-blind, placebo-controlled phase. Efficacy was determined by comparing the time to relapse between the asenapine and placebo groups, and relapse was defined by changes from baseline in the Positive and Negative Syndrome Scale total score and the Clinical Global Impression-Severity of Illness score. The asenapine group had a statistically significantly lower rate of relapse during the double-blind phase and longer time to relapse than did the placebo group.
The study was funded and conducted by Schering-Plough, which is seeking FDA approval of asenapine for long-term maintenance treatment of schizophrenia.
An abstract of the study is posted at <ex2.excerptamedica.com/09ecnp/abstracts/index.cfm?fuseaction=abs.prn&abstractID=P.3.c.057>.
Agomelatine, an antidepressant recently approved in Europe and currently under phase 3 development in the United States, was compared with fluoxetine in a randomized, double-blind, placebo-controlled study sponsored by its maker, Servier. More than 500 patients with a current episode of major depressive disorder and a 17-item Hamilton Rating Scale for Depression (HAM-D) total score of at least 25 were assigned to receive either agomelatine 25 mg to 50 mg (n=252) or fluoxetine 20 mg to 40 mg (n=263) for eight weeks. The agomelatine group had a statistically significantly greater decrease in HAM-D score from baseline than did the fluoxetine group, with a mean difference of 1.49 points between the groups. The percentage of patients achieving at least a 50 percent reduction in HAM-D score was 71.7 percent in the agomelatine and 63.8 percent in the fluoxetine group; this difference did not reach statistical significance.
Agomelatine is a melatonin MT1/MT2 receptor agonist and serotonin 5HT2c receptor agonist. The study results were presented at the September ECNP Congress.
An abstract of the study is posted at <ex2.excerptamedica.com/09ecnp/abstracts/index.cfm?fuseaction=abs.prn&abstractID=P%2E2%2Ec%2E026>.