Med Check
Publication: Psychiatric News
International Brief
Takeda Pharmaceutical Company of Osaka, Japan, announced last month that its London-based center for research and development decided to discontinue the development of ramelteon in Europe for the treatment of insomnia.
In September 2008, due to feedback received in May 2008 from the Committee for Medical Products for Human Use about the development requirements in Europe for this indication for ramelteon, Takeda withdrew its Marketing Authorization Application (MAA) originally submitted to the European Medicines Agency in March 2007. After examining the possibility of filing a new MAA, which would include new clinical data generated since the original submission, Takeda decided not to resubmit the MAA.
Ramelteon works by selectively targeting two melatonin receptors in the brain, MT1 and MT2, located in the suprachiasmatic nucleus; they regulate sleep-wake cycles and promote physiological sleep. Ramelteon was approved by the U.S. Food and Drug Administration (FDA) in July 2005 and by the Japanese Ministry of Health, Labour, and Welfare in April 2010; it is available in these countries as Rozerem.
Takeda says that it remains committed to ramelteon, believes it represents a valuable treatment option for patients, and is dedicated to conducting further research to evaluate the potential of ramelteon from different perspectives.
Regulatory Briefs
On December 12, the FDA's Psychopharmacologic Drugs Advisory committee will meet to discuss safety and efficacy issues for Alexza Pharmaceuticals' Adasuve (loxapine), an inhalation powder for the acute treatment of agitation associated with schizophrenia or bipolar I disorder in adults. The committee will focus on the drug's pulmonary safety.
Loxapine is an antipsychotic approved in oral and injectable forms. Adasuve uses Alexza's Staccato system to vaporize the drug for deep-lung inhalation and rapid treatment of agitation in patients with schizophrenic or bipolar disorder. Alexza is proposing the drug be used only in medically supervised settings, such as hospitals or psychiatric facilities.
Transcept Pharmaceuticals announced September 27 that it has resubmitted the New Drug Application for Intermezzo (zolpidem tartrate sublingual tablet) to the FDA. The resubmission follows a meeting between Transcept and the FDA to discuss issues raised in the FDA's July 2011 Complete Response Letter.
Transcept is developing Intermezzo as a prescription sleep aid for use as needed when a middle of the night awakening is followed by difficulty returning to sleep. Transcept and Purdue Pharmaceutical Products have entered into a collaboration agreement for the development and commercialization of Intermezzo in the United States.
Transcept is also developing TO-2061, a low-dose ondansetron-augmentation therapy for patients with obsessive-compulsive disorder who have not adequately responded to treatment with approved first-line pharmacotherapy.
Forest Laboratories and Gedeon Richter announced preliminary results last month from a phase 3 clinical trial of cariprazine (RGH-188), an investigational antipsychotic agent, in patients with acute mania associated with bipolar I disorder.
For the primary endpoint, the Young Mania Rating Scale, the data showed that cariprazine-treated patients with acute manic episodes experienced significant symptom improvement compared with placebo-treated patients seen as early as day 4 of treatment and at each subsequent time point studied. Further analyses of the data is planned to be completed soon. Cariprazine is also being investigated in clinical studies for patients with schizophrenia and bipolar depression and as an adjunct treatment in major depressive disorder.
Cariprazine, discovered by researchers at Gedeon Richter, is an orally active, potent dopamine D3 and D2 receptor partial agonist with high selectivity toward D3 receptors.
In September, the FDA required revision of the safety labeling information for Cymbalta (duloxetine hydrochloride) The Warnings and Precautions portion of the safety label now includes information about severe skin reactions, including erythema multiforme and Stevens-Johnson syndrome (SJS), that can occur with Cymbalta. The label explains, "The reporting rate of SJS associated with Cymbalta use exceeds the general population background incidence rate for this serious skin reaction (1 to 2 cases per million person years). The reporting rate is generally accepted to be an underestimate due to underreporting. Cymbalta should be discontinued at the first appearance of blisters, peeling rash, mucosal erosions, or any other sign of hypersensitivity if no other etiology can be identified." The medication guide for Cymbalta has also been changed to include language regarding severe skin reactions.
In September, the FDA required revision of the safety labeling information for Sustenna (paliperidone palmitate) and Risperdal (risperidone, in tablet, orally disintegrating tablet, and long-acting injection forms). The Warnings and Precautions portion of the safety label for both drugs now includes the statement, "Atypical antipsychotic drugs have been associated with metabolic changes that may increase cardiovascular/cerebrovascular risk. These metabolic changes include hyperglycemia, dyslipidemia, and body weight gain. While all of the drugs in the class have been shown to produce some metabolic changes, each drug has its own specific risk profile."
Orexigen Therapeutics announced in September that it is reviving its previously abandoned weight-loss drug Contrave (naltrexone/bupropion), after federal health officials outlined a plan that could bring the drug to market by 2014. This would position Contrave as the first new prescription weight-loss drug to reach the U.S. market in more than a decade.
The FDA rejected Contrave in February because of concerns the drug could increase heart problems. The company said in June it would not seek FDA approval for Contrave because of the government's "unprecedented" demands for additional safety studies. But the FDA has now agreed to a study that could be completed and reviewed by 2014. The study would involve 10,000 patients and take two years to gather the necessary data on heart side effects, according to Orexigen.
In September BioDelivery Sciences International (BDSI) announced preliminary findings from its phase 3 study of bioerodible mucoadhesive (BEMA) buprenorphine for the treatment of moderate to severe chronic pain in a mixed opioid-naive and opioid-experienced population. The randomized, placebo-controlled study's primary endpoint—overall pain intensity difference between BEMA buprenorphine and placebo—was not achieved. However, the manufacturer believes that the totality of the study results favors BEMA buprenorphine, including a near statistically significant difference between BEMA buprenorphine and placebo in the opioid-experienced group of patients in the trial. In addition, when eliminating the group of patients who did not titrate beyond the starting dose, researchers found a statistically significant difference between BEMA buprenorphine and placebo. BDSI plans to initiate a second efficacy study in the near future. 
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Published online: 18 November 2011
Published in print: November 18, 2011
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