Dimebolin hydrochloride (Dimebon™) is an orally-available, small-molecule agent that is in clinical testing for the treatment of Alzheimer's and Huntington's diseases-two progressive, devastating conditions with limited treatment options. Based on clinical and preclinical data generated to date, developer Medivation believes that dimebolin operates via a novel mechanism of action and may exert a neuroprotective effect in multiple areas of the central nervous system. Dimebolin appears to block a new target that involves mitochondrial pores, which are believed to play a role in the cell death that is associated with neurodegenerative diseases and the aging process. Dimebolin also blocks both cholinesterase and the NMDA receptor simultaneously. These two targets provide the mechanism of action for all FDA-approved drugs for Alzheimer's disease, although no marketed drug is known to have an effect on both pathways.

In July, the Huntington Study Group (HSG) reported that recruitment of participating sites for the DIMOND phase II trial (ClinicalTrials.gov identifier: NCT00497159), which will evaluate dimebolin in subjects with mild to moderate Huntington's disease (HD), is currently in progress. The randomized, double-blind, placebo-controlled phase II trial will enroll up to 90 patients at some 15 research centers in the U.S. and U.K. It is designed to evaluate the safety and tolerability of dimebolin during three months of treatment, as well as its effects on cognition, motor signs and overall functioning of HD patients aged 18 years or older. Patient enrollment will begin during the summer of 2007.

In June, the company reported that benefits of dimebolin hydrochloride over placebo in a double-blind, placebo-controlled phase II study in mild to moderate Alzheimer's disease (AD) were statistically significant on all five study endpoints at 12 months. In the multicenter, double-blind trial, 183 patients with mild to moderate AD were randomized to oral dimebolin (60 mg/day) or placebo for six months. Of these patients, 134 subsequently consented to continue treatment for up 12 months in their same treatment group. On the primary endpoint, the ADAS-cog, dimebolin caused an improvement over placebo of 6.9 points at one year. On the global function endpoint used in this study, the CIBIC-plus, dimebolin's benefit over placebo was 0.8 points at 12 months. Global function improved or remained stable in 69% of treated Alzheimer's disease patients after one year of dimebolin therapy. Dimebolin produced an aggregate benefit over placebo in this study that was larger at 12 months than at six. After a year of treatment, dimebolin's benefit over placebo was greater than six-month levels on the ADAS-cog (6.9 points vs. 4.0 points), CIBIC-plus (0.8 points vs. 0.6 points), and ADCS-ADL (5.2 points vs. 2.9 points) scales; however, only the ADAS-cog difference reached statistical significance. Dimebolin's benefit over placebo on the other two endpoints (the Mini Mental State Exam, [MMSE] and the Neuropsychiatric Inventory [NPI]) at six months was maintained at one year. Dimebolin-treated patients experienced significantly fewer serious adverse events than placebo-treated patients (3.4% vs. 11.7%). The most frequent adverse events associated with treatment were dry mouth, depressed mood/depression and sweating. Six-month phase III studies of dimebolin in AD will begin next year.

Dimebolin hydrochloride, which also acts as an antihistamine, is marketed in Russia by the Russian Academy of Sciences for the treatment of skin allergy and allergic rhinitis.

The information in this summary was derived from company sources and the Prous Science Integrity® and is current as of July 16, 2007. For continuously updated information on dimebolin, including new bibliographical references, Disease Briefings, clinical trials, regulatory information, patents and more, consult Integrity®.