Dimebon (latrepirdine) is an investigational compound indicated for the treatment of Alzheimer’s and Huntington’s disease. It is under development by the US-based biopharmaceutical company Medivation.
The mechanism of action of Dimebon has presented a new approach to the treatment of Alzheimer’s and Huntington’s. Medivation is planning to initiate trials for variants of Dimebon, known as analogues, which may have the ability to treat a range of diseases such as Parkinson’s and heart failure. If approved, Dimebon will provide a new treatment for Huntington’s, for which no known treatment exists.
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Dimebon, Alzheimer’s and Huntington’s
Alzheimer’s and Huntington’s are different types of dementia which progressively affect the brain leading to memory loss and the ability to perform daily activities.
Alzheimer’s is the most common type of dementia, accounting for 50-70% of cases. Current approved treatments are available only for mild to moderate Alzheimer’s.
These drugs are cholinesterase inhibitors that slow the increased cell death caused by the disease but do not prevent the cells from dying. It is estimated that 5.3 million people in the US suffer from the disease, a figure that is likely to increase.
Huntington’s develops through a specific genetic mutation that causes abnormalities in mitochondria, the part of cells that convert food into energy. The disease is hereditary and causes the degeneration and death of cells in many different parts of the brain leading to a loss in cognitive, memory and motor functions. People who inherit the mutation have a 100% chance of developing the disease.
Huntington’s causes death about 20 years after onset, making it one of the most prolonged illnesses in the world. It is estimated that in the US about 30,000 patients are suffering from the disease and another 20,000 are at risk of developing it.
Dimebon treatment
Dimebon has been used as an antihistamine in Russia for over two decades, primarily as an over-the-counter treatment for hay fever and allergies. Its applications as a treatment for Alzheimer’s and Huntington’s were discovered only recently.
In clinical studies conducted in patients suffering from Alzheimer’s and Huntington’s, Dimebon improved mitochondrial function that prevented cell death. The drug may have the ability to keep neurons alive and even make unhealthy neurons healthy again. Dimebon also demonstrated its ability to protect neurons from neurotoxic mutant human huntingtin protein, the main cause of Huntington’s.
Clinical trials
Medivation and Pfizer initiated two phase III studies, CONCERT and CONNECTION, to evaluate Dimebon in patients suffering from mild to moderate Alzheimer’s.
The phase III trials were initiated following positive results from a pivotal phase II Alzheimer’s trial. The randomised, double-blind, placebo-controlled 12-month trial was conducted on 183 patients with mild to moderate Alzheimer’s. About 81% of the patients treated in the study demonstrated significant improvements in cognition and overall functions.
The one-year CONCERT study will evaluate Dimebon in combination with Alzheimer’s drug Donepezil. The international, randomised, double-blind, placebo-controlled study enrolled 1,003 patients. UK’s Glasgow Memory Clinic is conducting the trial across 100 sites in the US, EU, Australia, New Zealand and Western Europe.
Results of the study are expected by first half of 2012. The CONCERT trial is not being carried out in patients who are already taking other anti-dementia medications.
In March 2010, the six-month double-blind, placebo-controlled CONNECTION study, which evaluated Dimebon as monotherapy, was completed. The study was conducted on 598 patients across 63 centres in the US, Europe and South America.
The results of the study, however, demonstrated that Dimebon did not meet the primary and secondary efficacy endpoints.
In November 2009, Medivation and Pfizer initiated two more studies, CONSTELLATION and CONTACT, to evaluate Dimebon in patients suffering from moderate to severe Alzheimer’s.
The CONSTELLATION study is a randomised, double-blind placebo-controlled study that enrolled 570 patients across 80 sites in the US, Canada and Europe. The study will assess Dimebon in combination with Memantine in improving Alzheimer’s symptoms.
The CONTACT study is also a randomised, double-blind, placebo-controlled study that will evaluate Dimebon in combination with Donepezil in improving neuropsychiatric symptoms. The study has enrolled 600 patients across 75 sites in Europe and South America.
Phase III trials for Huntington’s were taken up following positive results from a Phase II trial conducted on 91 patients with mild to moderate Huntington’s in 2006. In 2008, Medivation announced positive results from the study, which indicated that Dimebon helped significantly improve the cognitive function in patients.
A phase III trial, HORIZON, evaluated the safety and efficacy of Dimebon in 403 patients with mild-to-moderate Huntington’s.
On 11 April 2011, Pfizer and Medivation announced results from the HORIZON study, which showed that Dimebon did not meet the primary efficacy endpoints.
