Second Phase III study failing to meet its endpoints prompted firms to end partnership.
Medivation and Pfizer are axing development of dimebon on the back of poor Phase III results from an Alzheimer disease (AD) trial. The Concert study did not meet either of its co-primary endpoints of improving cognition or self care and daily function. The companies have thus decided to end their co-development and marketing collaboration.
The decision is not surprising as the companies had previously stopped a Huntington disease late-stage trial and also reported that another Alzheimer disease study, Connection, had failed to meet its primary and secondary endpoints. The companies are now terminating the remaining two AD studies: Contact and Constellation.
While the decision in Huntington disease came last April, Connection data was announced in March 2010. Connection was conducted in patients with mild-to-moderate disease. Concert in the same setting evaluated dimebon along with donepezil HCL tablets, while Contact and Constellation trials tested the drug in patients with moderate-to-severe disease taking currently approved medications.
In Concert dimebon did not achieve statistically significant results in either the Alzheimer’s Disease Assessment Scale – cognitive subscale (ADAS-cog) or the Alzheimer’s Disease Cooperative Study – Activities of Daily Living (ADCS-ADL). Dimebon was generally well tolerated in the study. A full analysis of the results from Concert will be conducted and submitted for presentation at an upcoming scientific congress.
The study was a 12-month global randomized, double-blind, placebo-controlled trial that enrolled 1,003 patients with AD. Patients on a stable dose of donepezil for at least four months were randomized to one of three treatment groups: dimebon 20 mg three times per day, dimebon 5 mg three times per day, or placebo.
Pfizer originally paid $225 million up front for global rights to dimebon in September 2008. It also agreed to pay 60% of development expenses, up to $500 million in milestones related to clinical and regulatory success, and additional success-based fees tied to sales achievements.
In the AD space Pfizer is left with a mAb in Phase III development, bapineuzumab, and three Phase I stage candidates: PF-05297909, PF-05236812, and PF-05212377. Medivation has only one other drug in clinical development: MDV3100 for prostate cancer.