Med Check

Shionogi Inc. announced in October that the U.S. Food and Drug Administration (FDA) has approved the nonstimulant medication Kapvay (clonidine hydrochloride) extended-release tablets for the treatment of attention-deficit/hyperactivity disorder (ADHD) in children and adolescents aged 6 to 17 years. Two phase 3 studies showed that children and adolescents with ADHD experienced statistically significant improvements in core symptoms of inattention, hyperactivity, and impulsivity after treatment with Kapvay.

The FDA issued a final rule in October that clarifies what safety information must be reported during clinical trials of investigational drugs and biologics. This information includes findings from clinical or epidemiological studies that suggest a significant risk to study participants, serious suspected adverse reactions that occur at a rate higher than expected, and serious adverse events from bioavailability and bioequivalence studies. The rule also provides examples of evidence suggesting that an investigational product may be the cause of a safety problem. In addition, the rule revises definitions and reporting standards so that they are more consistent with two international organizations, the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use and the World Health Organization's Council for International Organizations of Medical Sciences.

The final rule is published in the Federal Register at <http://frwebgate.access.gpo.gov/cgi-bin/getdoc.cgi?dbname=2010_register&docid=fr29se10-3.pdf>.

The FDA unveiled a report in October outlining the agency's plans to advance its Regulatory Science Initiative. The initiative describes the science of developing new tools, standards, and approaches for assessing the safety, efficacy, quality, and performance of FDA-regulated products. The report provides examples of current FDA activities in regulatory science and also considers how advancements in the field can help deliver better, safer, more innovative products in seven public health areas.

The report, “Advancing Regulatory Science for Public Health,” is posted at <www.fda.gov/FDAgov/ScienceResearch/SpecialTopics/RegulatoryScience/default.htm>.

In October the FDA approved Vivitrol (naltrexone) in a monthly injection form to treat addiction to opioids. Vivitrol is already approved for the treatment of alcoholism. Approval of the drug, which is marketed by Alkermes Inc., was based on company studies that showed patients taking Vivitrol were more likely to be free of opioids than those taking a dummy injection. The typical Vivitrol patient reported opioid-free urine samples 90 percent of the time, compared with 35 percent for those not taking the drug.

FDA declined in October to approve Alexza Pharmaceuticals Inc.'s AZ-004 drug to treat agitation in patients with schizophrenia or bipolar disorder, potentially delaying approval of its lead drug by more than a year. In a complete response letter to the company, the FDA said it was concerned about data from three early-stage pulmonary safety studies that showed some adverse respiratory events associated with AZ-004.

AstraZeneca is launching a new campaign called “Take on Depression” through a “Take on Depression” Facebook page and a @FaceDepression Twitter feed to support, educate, and inspire those affected by bipolar depression and major depressive disorder. The “Take on Depression” Facebook page will provide tools and resources to individuals who are struggling to manage their symptoms of bipolar depression and major depressive disorder. The @FaceDepression Twitter feed will provide articles, links to Web sites, tips, and community events that will help people learn more about their illness and have a more effective dialogue with their physician. To “like” the “Take on Depression” Facebook page, visit <www.facebook.com/TakeonDepression>. To become a follower of “FaceDepression” on Twitter, visit <http://twitter.com/FaceDepression>.

Novartis Pharmaceuticals Corp. agreed in October to pay $422.5 million in civil and criminal fines for promoting Trileptal (oxcarbazepine) for unapproved uses, including bipolar disorder and neuropathic pain. (The drug is approved for treatment of epilepsy.) Under the settlement, Novartis agreed to plead guilty and pay a criminal fine of $185 million for off-label marketing of Trileptal. It also will pay $237.5 million in civil penalties for off-label marketing and for offering financial inducements for doctors to prescribe Trileptal and other Novartis medicines.

In October the FDA accepted Accera's investigational new drug (IND) application to conduct a phase 2-3 clinical study of its product Axona/AC-1202 in patients with mild to moderate Alzheimer's disease. The AC-1204 Long-Term Efficacy Response Trial (ALERT) will be a six month, double-blind, randomized, placebo-controlled, parallel-group Approximately 400 study subjects are anticipated to enroll in as many as 30 clinical sites within the United States.

Accera has completed four clinical trials with similar compounds in elderly normal volunteers and in patients with memory impairment or mild to moderate Alzheimer's. In these trials, patients receiving Axona (AC-1202) for up to 90 days experienced cognitive improvement compared with subjects taking placebo. These treatment effects were notably significant among patients who were not carriers of the apolipoprotein E4 allele (ApoE4), a genetic risk factor associated with a higher probability of developing Alzheimer's.

Tasly Pharmaceutical Co. Ltd. and ProteoTech Inc. announced in October an agreement to develop ProteoTech's novel small molecule, Exebryl-1(R), for the treatment of mild to moderate Alzheimer's disease. Exebryl-1(R) has been shown to inhibit beta-amyloid protein aggregate formation in the brain, as well as disaggregate amyloid plaques that are already present. The drug has also shown specificity against tau protein aggregates.

Otsuka Pharmaceutical Development and Commercialization Inc. announced in October it will file a new drug application for intramuscular depot aripiprazole, following successful demonstration of efficacy in the Aripiprazole Intramuscular Depot Study in Schizophrenia–U.S. Aripiprazole is sold under the brand name Abilify.

Results announced in October from a national survey of Alzheimer's disease caregivers found that the 67 percent of Alzheimer's caregivers surveyed said changes in cognitive symptoms were among their main concerns.

The three greatest caregiver concerns about the progression of their loved one's disease were memory loss (41 percent), personal safety (33 percent), and confusion (27 percent).

The survey was conducted by Harris Interactive in September 2010 for Eisai Inc. and Pfizer Inc. in partnership with the Alzheimer's Foundation of America. A total of 524 nonprofessional adult Alzheimer's caregivers, including those of mild, moderate and severe Alzheimer's patients, were surveyed.

Fifty-five percent of the caregivers said caring for their loved one has taken a toll on their own health, and 60 percent of the caregivers said they feel overwhelmed.