Research was conducted in both Russia and western nations into potential applications as a neuroprotective drug to treat Alzheimer's disease and, possibly, as a nootropic, as well. After a major phase III clinical trial for Alzheimer's disease (AD) treatment failed to show any benefit, three other AD trials continued. Major industry-based development in this indication essentially stopped after another Phase III trial suffered the same fate in 2012. Latrepirdine failed in the phase III trial for Huntington disease.
Latrepirdine is an orally active, small molecule compound that has been shown to inhibit brain cell death in animal models of Alzheimer's disease and Huntington's disease. Research suggests it may also have cognition-enhancing effects in healthy individuals, in the absence of neurodegenerative disease pathology. However, because of negative results in human clinical trials, the drug remains unlicensed for any neurodegenerative condition.
Alzheimer's disease: failed in Phase III clinical trials
Latrepirdine attracted renewed interest in 2009 after being shown in small preclinical trials to have positive effects on persons suffering from Alzheimer's disease. Animal studies showing potential beneficial effects on Alzheimer's disease models were shown in Russian research in 2000. Preliminary results from human trials have also been promising. In an initial six-month phase II trial, results have shown significant improvement over placebo at 12 months. Latrepirdine showed promising results in a phase III-equivalent, double-blind trial in Russia with mild–moderate stage patients. In April 2009, Pfizer and Medivation initiated a phase III trial (CONCERT study) aiming for FDA approval. In March 2010, Pfizer announced that this clinical trial failed to show any benefit for the treatment of Alzheimer's disease patients.
In March 2010, the results of a clinical trial phase III were released; the investigational Alzheimer's disease drug dimebon failed in the pivotal CONNECTION trial of patients with mild-to-moderate disease.
With CONCERT, the remaining Pfizer and Medivation Phase III trial for latrepirdine in Alzheimer's disease failed in 2012, effectively ending the development in this indication.
A Cochrane meta-analysis of the three pivotal phase III efficacy trials found no significant effect of latrepirdine on cognition and function in mild-to-moderate Alzheimer's patients, though there appears to be a modest benefit for overall behavior disturbances.
In April 2011, latrepirdine failed in a phase III clinical trial of patients affected with Huntington's disease. The trial was sponsored by Medivation Inc. and Pfizer.
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"Pfizer and Medivation Initiate Phase 3 Trial of Dimebon Added to Donepezil in
Patients with Alzheimer's Disease" Apr 2009
^[clinicaltrials.gov] "A Phase 3 Study To Evaluate The Safety And Tolerability Of Dimebon Patients With Mild To Moderate Alzheimer's Disease"
^[clinicaltrials.gov] "A Phase 3 Efficacy Study Of Dimebon In Patients With Moderate To Severe Alzheimer's Disease"
^[clinicaltrials.gov] "An Extension To The B1451027 Protocol To Evaluate The Long Term Safety And Tolerability Of Dimebon In Patients With Alzheimer's Disease"
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