• Bristol-Myers Squibb and Otsuka Pharmaceutical Co. of Japan announced the filing of a supplemental New Drug Application (sNDA) to the FDA for Abilify (aripiprazole), jointly developed and marketed by the pair. Approved for the treatment of schizophrenia last November, the companies are seeking to add an indication for long-term treatment of schizophrenia.
• Janssen Pharmaceutica announced its submission of an sNDA for a once-daily formulation of Reminyl (galantamine), which is approved for the treatment of mild to moderate Alzheimer’s disease. The extended-release formulation would ease medication administration in people with dementia.
• The U.S. Federal Trade Commission, following action last month by the European Union, announced that it had completed negotiations with Pfizer and Pharmacia, moving the two companies closer to their expected $52 billion merger. When the deal is final, the combined company will be by far the world’s largest pharmaceutical business. The companies declined to release details but said that the agreement with the FTC requires the divestiture of certain products, none of which was termed "vital to business interests," to avoid antitrust concerns.
• GlaxoSmithKline’s closely watched patent fight over Paxil (paroxetine) ended with a mixed ruling in federal district court in Chicago last month when the judge upheld the validity of the challenged Paxil patent, but said that a proposed paroxetine generic, to be marketed by Apotex unit TorPharm, did not violate that remaining patent. GSK has said it will appeal. If the ruling stands, generic paroxetine could be available in the United States as early as late September.
• Eli Lilly & Co. is facing ever-mounting pressure over its blockbuster Zyprexa (olanzapine). Amid threatened patent challenges, personal-injury attorneys last month filed the first two of what are expected to be several dozen lawsuits claiming the company knew about and hid the drug’s reported link to adverse effects on glucose and lipid metabolism. The suits, filed in a San Francisco court, seek class-action status.
• Risperdal Consta (risperidone), Janssen’s long-acting injectable form of the atypical antipsychotic, was approved in Spain last month, bringing the number of countries where the drug is marketed to 16. The FDA last year issued a nonapprovable letter for the formulation, based, the company said, on "questions related to certain aspects of the preclinical data." Janssen had previously said it would refile the U.S. application to address the FDA’s concerns.
• Researchers at the Mayo Clinic in Jacksonville, Fla., have received a patent for a new method of drug delivery capable of slipping past the blood-brain barrier. The finding was a surprise to the researchers, who were trying to develop a new way to deliver gene therapy inside cells. Neuropharmacologists at Mayo hope the discovery could lead to new ways to reach brain cells and fight diseases on a molecular level.
• Shire Pharmaceuticals announced last month that it had acquired the rights to market MethyPatch from Noven Pharmaceuticals. Marketing the methylphenidate patch worldwide, the company said, "is in line with Shire’s strategy of maintaining leadership in the ADHD market."
• A comprehensive review of the scientific literature has linked the dietary supplement ephedra to heart, gastrointestinal, central nervous system, and psychiatric problems. The authors also found that there is insufficient evidence to support any use of the supplement to enhance athletic performance or promote long-term weight loss. The report reviews more than 16,000 adverse event reports, revealing five deaths, five myocardial infarctions, 11 cerebrovascular accidents, four seizures, and eight cases linking ephedra to psychiatric symptoms, including aggression, rage, mania, paranoia, and psychosis.
• The price of bringing a new drug to market rose on average more than 7 percent above the rate of general inflation for calendar year 2000. Out-of-pocket costs were estimated to be $403 million to submission of a New Drug Application, and more than $800 million when the marketing prelaunch is included.
(J Health Econ
• Securing approval for a New Drug Application may be significantly affected by how clinical trials are structured. In a review of 52 antidepressant clinical trials, 59.6 percent of flexible-dose trials ended in statistically significant results compared with placebo, while only 31.4 percent of fixed-dose trials resulted in a statistically significant difference compared with placebo. In addition, the primary goal of demonstrating a dose-response curve is inherently impossible in a fixed-dose study.
• In a review of clinical trials data for nine antidepressants approved by the FDA between January 1985 and January 2000, the rate of suicide was found to be not statistically significantly different among those assigned to an SSRI, a standard comparison antidepressant, or placebo. Of 48,277 patients enrolled in the nine clinical trials, 77 committed suicide, for an overall rate of 0.16 percent.
(Am J Psychiatry
• Memantine, an NMDA receptor antagonist, appears to be a safe adjunct therapy for the treatment of dementia when combined with acetylcholinesterase inhibitor therapy. Approved in Europe, the drug is pending approval by the FDA as an adjunct therapy for Alzheimer’s dementia. A review of German postmarketing data revealed that memantine was well tolerated, and no adverse drug reactions were reported when the drug was added to existing donepezil (Pfizer’s Aricept) therapy.
(Int Clin Psychopharmacol
• Amantadine (Endo’s Symmetrel and generics), which has been traditionally used to reduce symptoms in influenza, is also known to exhibit prominent effects on dopaminergic, monoamine oxidase, and NMDA receptors. A new study indicates it may be a safe and effective adjunct drug, along with a traditional antidepressant, in treatment-resistant depression. Side effects include dry mouth and sedation.
(Int Clin Psychopharmacol
• In a retrospective chart review, lamotrigine (GSK’s Lamictal) appears to be a safe and effective add-on for treatment-resistant unipolar depression in addition to its demonstrated efficacy in bipolar disorder. Seventy-six percent of the study patients who had failed on prior antidepressant therapy improved after the anticonvulsant was added. Side effects included somnolence, headache, dizziness, and fatigue.
(Int Clin Psychopharm
• The simultaneous blockade of 5HT2A receptors by existing medications—such as risperidone (Janssen’s Risperdal), olanzapine (Lilly’s Zyprexa), and mirtazapine (Organon’s Remeron)—and activation of an unknown group of other serotonin receptors through inhibition of reuptake—the SSRIs/SNRIs—appears to show a synergistic effect on efficacy, larger than either strategy alone. Anecdotal evidence links combination therapy to better results in treatment-resistant depression and refractory obsessive-compulsive disorder. This could lead to a search for a compound that could exhibit both properties in one medication.
• Methadone treatment helps to quell cravings and consequent drug-seeking behavior in patients addicted to heroin. A new study indicates that methadone also reversed potentially dangerous changes in blood flow known to accompany heroin use. The findings suggest that methadone modulates not only behavior but also neurovascular regulation.
2003; 28:562-568) ▪