Dimebon Tanks (Along With Medivation Stock) in Phase 3 Alzheimer Trial
Someday I'm going to learn to capitalize on the overblown expectations and inevitable letdown of AD drug development.
Dimebon (latrepirdine), the nonselective antihistamine that Pfizer shelled out millions for, failed to improve cognition or global functioning in a placebo-controlled phase 3 study of patients with mild-moderate Alzheimer disease. The disappointing results were distributed today by way of press release from the drug's codevelopers, Medivation and Pfizer.
In a double-blind study of 598 individuals with AD in North America, Europe, or South America, Dimebon 20 mg tid was no better than placebo for improving or delaying declines in cognition (as measured with the ADAS-cog) or global functioning (as measured with the CIBIC-plus) at 6 months. Measures of secondary endpoints (eg, activities of daily living) were, likewise, similar between Dimebon- and placebo-treated patients.
As expected, the most frequently reported adverse events with the antihistamine were somnolence and dry mouth. A 5-mg treatment arm and another, large phase 3 safety study revealed consistent drug tolerability. For what it's worth, the phase 3 safety study showed that the drug can be taken with common AD medications, like cholinesterase inhibitors (eg, Aricept; Pfizer) or memantine (Namenda; Forest).
Results from the phase 3 efficacy study were to be used in conjunction with positive results from a phase 2 Russian study to support FDA approval. But, evidently, no more.
In 2008, Pfizer agreed to pay Medivation $225 million upfront and another $500 million when the drug was approved. The agreement also conferred licensing rights to Pfizer for use of the drug in Huntington disease. Last month, results from a 90-day safety trial of Dimebon in HD showed that the drug may improve cognition.
The price of Medivation stock dropped nearly 30 points on release of the phase 3 trial results, from $40.12 to $12.88.
ADAS-cog = Alzheimer's Disease Assessment Scale-cognitive subscale; CIBIC-plus = Clinician's Interview-Based Impression of Change Plus Caregiver Input.
Photograph: Atrophied brain from person with AD from National Institute on Alcohol Abuse and Alcoholism.
