Med Check
Industry Briefs
• On June 20, Ortho-McNeil-Janssen Pharmaceuticals announced a recall of specific lots of Risperdal (risperidone) 3 mg tablets and 2 mg tablets. The recall stems from consumer reports of an uncharacteristic odor thought to be caused by trace amounts of TBA (2,4,6 tribromoanisole). TBA is a byproduct of a chemical preservative sometimes applied to wood used in construction of pallets on which materials are transported and stored. While not considered toxic, TBA can generate an offensive odor, and a small number of patients have reported temporary gastrointestinal symptoms.
The FDA's recall notice is posted at <www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm259901.htm>.
• On June 20, Pfizer and Acura Pharmaceuticals announced marketing approval from the Food and Drug Administration (FDA) for Oxecta (oxycodone) tablets (CII). Oxecta is indicated for management of acute and chronic moderate to severe pain when the use of an opioid analgesic is appropriate. Oxecta is the first immediate-release oxycodone medicine that applies technology designed to discourage common methods of tampering associated with opioid abuse and misuse. This aversion technology is a unique composition of commonly used pharmaceutical ingredients. Pfizer is licensing the technology from Acura. There is no evidence as yet that Oxecta has a reduced abuse liability compared with immediate-release oxycodone.
• On June 30, Forest Laboratories announced that Viibryd (vilazodone) tablets are available at pharmacies throughout the United States. Viibryd is indicated for the treatment of adults with major depressive disorder (MDD). The FDA approved Viibryd as a new molecular entity in January, making it the only approved selective serotonin reuptake inhibitor (SSRI) and 5HT1A receptor partial agonist. The mechanism of Viibryd's antidepressant effect is not fully understood but is thought to be related to its enhancement of serotonergic activity in the central nervous system through selective inhibition of serotonin reuptake.
The efficacy of Viibryd in MDD treatment was established in two eight-week, randomized, double-blind, placebo-controlled studies of 861 adult patients with MDD, 436 of whom received Viibryd. In these studies, patients were titrated over two weeks to a dose of 40 mg of Viibryd once daily with food. Viibryd was superior to placebo in the improvement of depressive symptoms as measured by the mean change from baseline to week 8 in the Montgomery-Asberg Depression Rating Scale.
• On July 12, Zogenix and Durect announced a development and license agreement under which Zogenix will be responsible for the clinical development and commercialization of a proprietary, long-acting injectable formulation of Relday (risperidone) using Durect's controlled-release formulation technology in combination with Zogenix's needlefree, subcutaneous drug-delivery system. The companies will also share nonclinical development responsibilities. Zogenix expects to initiate clinical studies for the new product candidate in patients with schizophrenia in early 2012 following filing of an Investigational New Drug Application. The companies expect that if approved, Relday will be the first once-monthly, subcutaneous antipsychotic available in a needle-free delivery system to enter the long-acting injectable antipsychotic market and will provide a new treatment option for patients who currently use daily oral antipsychotics.
• On July 11, Titan Pharmaceuticals announced positive results from its phase 3 confirmatory clinical study of Probuphine, an implantable form of buprenorphine that allows continuous delivery of the medication for six months after each treatment. The product was developed to reduce the risk of diversion and abuse while assuring compliance with treatment and potentially improved medical outcomes. The study evaluated the safety and efficacy of Probuphine in patients with opioid dependence, and results were clinically meaningful and statistically significant as demonstrated by two analyses, both of which confirmed the efficacy of Probuphine compared with placebo. Probuphine also met a key trial objective by demonstrating non-inferiority to treatment with the approved drug Suboxone (buprenorphine and naloxone).
Probuphine was well tolerated, with a safety profile similar to that seen in previous studies. Titan expects that additional study findings will be reported in the coming weeks and said study results will be presented at scientific meetings later this year. Titan plans to request a meeting with the FDA for this fall to review the Probuphine development program and plans for filing a New Drug Application.
Regulatory Briefs
• On June 10, the FDA approved Potiga (ezogabine) tablets for use as an add-on medication to treat seizures associated with epilepsy in adults.
Potiga was approved for treatment of partial seizures, the most common type of seizure seen in people with epilepsy. Potiga is the first neuronal potassium channel opener developed for epilepsy treatment. Although the mechanism of action is not firmly established, the drug may act as an anticonvulsant by reducing excitability through the stabilization of neuronal potassium channels in an "open" position.
Potiga may cause neuropsychiatric symptoms, including confusion, hallucinations, and psychotic symptoms. When Potiga is discontinued, these symptoms usually resolve within seven days. Like other antiepileptics, Potiga may cause suicidal thoughts or actions in a very small number of people.
Potiga was developed by Valeant Pharmaceuticals North America and will be distributed by GlaxoSmithKline.
• On June 30, the FDA informed the public that children born to mothers who take the antiseizure medication valproate sodium or related products (valproic acid and divalproex sodium) during pregnancy have an increased risk of lower cognitive test scores than children exposed to other antiseizure medications during pregnancy. The FDA's conclusion is based on results of epidemiologic studies showing that children born to mothers who took valproate sodium or related products throughout their pregnancy tend to score lower on cognitive tests (IQ and other tests) than children born to mothers who took other antiseizure medications during pregnancy.
The FDA's Drug Safety Communication is posted at <www.fda.gov/Drugs/DrugSafety/ucm261543.htm>.
• On July 19, the New York Times reported that AstraZeneca is adding a new cardiac warning to the label of its antipsychotic Seroquel (quetiapine) at the request of the FDA. The new label, said the Times, notes that Seroquel and extended-release Seroquel XR "should be avoided" in combination with at least 12 other medicines linked to prolongation of the QT interval. The revised label also cautions about use of the drug by the elderly and people with heart disease.
Research Briefs
• Alkermes announced on July 7 topline results from a phase 2 clinical study of ALKS 33 in the treatment of binge-eating disorder. This randomized, doubleblind, placebo-controlled, 12-week study was designed to assess safety and efficacy of daily oral administration of ALKS 33 or placebo in 68 patients with binge-eating disorder. While ALKS 33 demonstrated a significant reduction from baseline in the endpoint of self-reported weekly bingeeating episodes, the reduction was not significantly different from that observed with placebo. Based on these results, the company has determined that future studies of the drug for the binge-eating indication are not planned.
ALKS 33 remains in development for other central nervous system indications, based on its favorable characteristics of once-daily dosing, limited hepatic metabolism, and durable pharmacologic activity in modulating brain opioid receptors. ALKS 33 is being evaluated as a potential treatment for alcohol dependence and, in combination with buprenorphine as ALKS 5461, for cocaine addiction and treatment-resistant depression.
• On July 19, Allon Therapeutics announced new findings that 12 weeks of treatment with davunetide appears to prevent cortical thinning of important parts of the brains of schizophrenia patients.
The new data emerged from the ongoing analysis of magnetic resonance imaging results by a group of scientists and physicians led by Jeffrey Lieberman, M.D., chair of the Department of Psychiatry at Columbia University College of Physicians and Surgeons and director of the New York State Psychiatric Institute.
"The new data showed that in the 23-patient study, the thickness of the cortex in specific regions of the brain decreased in the eight schizophrenia patients given placebo, whereas it did not change in the 15 patients treated with davunetide," Lieberman said in information released by Allon Therapeutics. "Schizophrenia is a progressive, neurodegenerative disease in which cortical thinning is believed to be responsible for some of the clinical symptoms. This preliminary evidence of a davunetide treatment effect is interesting and merits replication in a larger study of schizophrenia patients. This new finding is consistent with the hypothesis that davunetide prevents brain atrophy by a mechanism thought to involve the preservation of microtubule function."
The analyses showed that the greatest treatment effect was seen in the dorsolateral prefrontal and temporal cortical regions of the brain. These areas are known to be impacted in cognitive-impairment associated with schizophrenia.
The imaging studies were funded by the Brain and Behavior Research Foundation (formerly known as the National Alliance for Research on Schizophrenia and Depression) and Allon Therapeutics. The phase 2a trial was managed by TURNS (Treatment Units for Research on Neurocognition and Schizophrenia), a clinical-trial network of eight academic medical institutions led by the University of California at Los Angeles, with substantial financial support from the National Institute of Mental Health.
