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Alzheimer’s disease (AD) is a progressive neurodegenerative condition that affects brain areas involved in memory, cognition, judgment, language, and behavior. AD is the most common cause of late-life dementia and half of the people over 85 may suffer from it. Five drugs are currently approved to treat AD in the United States; however, all of them treat the symptoms of Alzheimer’s but not the underlying cause of the disease.
The antihistamine Dimebon was first used as an allergy drug in Russia in the early 1980s. This orally-available, small molecule has been shown to inhibit brain cell death in preclinical models (animal studies) relevant to Alzheimer’s disease and Huntington’s disease in 2000, making it a potential treatment for these and other neurodegenerative diseases. Medivation is currently evaluating Dimebon in clinical trials for both Alzheimer’s disease and Huntington’s disease.
The first pivotal clinical trial of Dimebon by Medivation in Alzheimer’s disease was a random, double-blind, placebo-controlled trial of 183 patients with mild-to-moderate Alzheimer’s disease and demonstrated that Dimebon improved the clinical course of the disease. The trial’s recently published results show that compared with placebo treatment, patients treated with Dimebon, for six months or for a full year, experienced statistically significant improvements in all the key aspects of the disease: memory and thinking, activities of daily living, behavior, and overall function. Patients treated with Dimebon were significantly improved at six months over baseline on all measures and the drug’s benefit over placebo continued to increase throughout the 12-month treatment period. At the end of 12 months, Dimebon-treated patients preserved their starting level of function on each measure of Alzheimer’s disease. Moreover, Dimebon was well-tolerated throughout the trial – there was no difference between the Dimebon and placebo groups in the number of patients with adverse events.
Additional analyses of the Dimebon’s study data also showed a benefit to caregivers, as behavioral improvements in Dimebon-treated patients resulted in a significant decrease in caregiver distress at six months and at one year compared with the distress of caregivers of placebo-treated patients. Caregivers of Dimebon-treated patients also saved approximately one hour per day assisting patients with activities of daily living after six months of treatment.
The mental function tests and interviews with caregivers confirmed improvements or disease stabilization in 81% of the Dimebon-treated patients after six months. This clinical study is the first Alzheimer’s disease study in which a drug has achieved statistically significant benefits of this breadth, size, and duration in a one year, well-controlled trial.
Dimebon has not been compared to the currently approved Alzheimer’s drugs, three of which inhibit the activity of a brain enzyme called cholinesterase, and slow down the deterioration of neurons in the brain area that governs memory and thinking. However, the study indicates that Dimebon has a mechanism of action that is unrelated to its antihistamine properties. According to currently available clinical and preclinical data the investigators believes that Dimebon works through a novel mechanism of action improving mitochondrial function.
Medivation hopes to market Dimebon for the treatment of Alzheimer’s in the U.S. and has already initiated confirmatory pivotal phase three Alzheimer’s disease trials in the U.S., Europe, and South America (called The CONNECTION Study) in the second quarter of 2008.
It is noteworthy that Medivation has recently announced positive safety and efficacy results from its phase two trial of Dimebon for the treatment of Huntington’s disease and plans to also further investigate and confirm these phase two trial’s positive results.
Other Alzheimer’s disease related researches previously covered by TFOT pinpointed a possible physical origin of the disease and developed a method to decrease the neuron loss rate in mice bearing Alzheimer’s disease and ALS analogues.
