Merck & Co suffered a late-stage pipeline disappointment after the pharma company decided to call a halt to the development of preladenant, an adenosine A2A receptor antagonist being tested in Parkinson’s disease.
Despite encouraging results in phase II, the company revealed yesterday that three phase III trials found that preladenant was no more effective than placebo when given either alone or in combination with levodopa in Parkinson’s.
Merck said the decision to terminate the programme was not based on any safety issues with the drug, which was originally developed by Schering-Plough.
“Parkinson’s disease is very complex, making it difficult to treat patients and develop novel therapeutic approaches,” said Merck’s VP of neuroscience and ophthalmology clinical research David Michelsen.
“We are committed to neuroscience research and will be conducting further analyses of the data to inform the scientific community’s efforts in finding new approaches to treat this debilitating disease,” he added.
Adenosine A2A receptor antagonists modulate the production of dopamine, glutamine and serotonin in specific regions of the brain.
Drugs acting by this mechanism have been shown to reduce the time when the therapeutic effect of levodopa is lost – an unpredictable feature of Parkinson’s known as the ‘off’ effect. In a phase II trial, preladenant as an adjunct to levodopa decreased “off” time compared to placebo.
The lack of efficacy in phase III for preladenant is something of a death rattle for the adenosine A2A receptor antagonist category in Parkinson’s, although Kyowa Hakko Kirin’s istradefylline (KW 6002) has been filed for approval in Japan as a once-daily therapy.
Istradefylline failed to secure approval in the US, however, and Kyowa Hakko Kirin subsequently out-licensed US rights to istradefylline to Biovail (now Valeant), which bowed out of the deal in 2011.
Meanwhile, Lundbeck was also working in this area with its Lu AA47070, but discontinued this project a couple of years ago, while Vernalis and Biogen Idec dropped their own candidate vipadenant in 2010.