Neurogen Corporation has acquired from Wyeth Pharmaceuticals, a division of Wyeth, worldwide development and commercialization rights to Aplindore, a small molecule partial agonist for the D2 dopamine receptor.
Neurogen expects to commence phase II trials in Parkinson's disease and restless legs syndrome (RLS) with Aplindore during 2007, following the manufacture of clinical supplies.
Aplindore was initially developed by Wyeth for schizophrenia and has been studied in six phase I and phase II clinical trials involving over 100 healthy volunteers and over 100 schizophrenic patients. The drug demonstrated excellent brain receptor occupancy and pharmacologic activity at low doses, but proved inappropriate for the treatment of this disease at the dose range tested. Neurogen believes that at doses significantly lower than those used in previous trials, Aplindore may prove to be an attractive treatment for Parkinson's disease and RLS.
Neurogen acquired worldwide rights to Aplindore for an initial license fee payment of $3 million, in an agreement signed November 21, 2006. Neurogen will also pay Wyeth milestone payments upon the successful achievement of clinical development and regulatory events, and royalties on worldwide sales.
William H. Koster, PhD, president and CEO of Neurogen, said, "We're very pleased to have in-licensed a phase II compound with the excellent prospects of Aplindore, in a highly competitive environment for good in-licensing opportunities. While we possess an outstanding drug discovery platform here at Neurogen, we have also been looking for the right mid-stage clinical candidate to augment our internally discovered compounds. The market for Parkinson's disease and RLS is continuing to grow significantly and we believe there is need for improvement in dosing regimens and side effect profiles that may be made possible by Aplindore."
Dopamine agonists currently available for the treatment of Parkinson's disease and RLS are full agonists at D2 receptors and require a long titration period-up to seven weeks in Parkinson's disease and four weeks in RLS. Titration is the process of establishing the appropriate dose of a drug for a particular patient by increasing doses incrementally over a period of time. Currently available dopamine agonist treatments for Parkinson's disease produce side effects in many patients that include daytime somnolence or drowsiness, dyskinesias (sudden episodes of abnormal involuntary movements), and hallucinations. While dopamine agonists have proved effective in the treatment of RLS, many patients still suffer side effects of augmentation (a worsening of symptoms), nausea, constipation, and hypotension. Neurogen believes that Aplindore may provide an improved side-effect profile and shorter dosing titration period in Parkinson's disease and RLS due to partial agonism of the D2 receptor, as compared with the full agonist drugs currently in use.
Parkinson's disease is a brain disorder that occurs when certain nerve cells (neurons) in a part of the brain called the substantia nigra die or become impaired. Normally, these cells produce a vital chemical, dopamine, which allows smooth, coordinated function of the body's muscles and movement. When approximately 80 per cent of the dopamine-producing cells are damaged, the symptoms of Parkinson's disease appear. The loss of dopamine production in the brain causes the primary symptoms of Parkinson disease. The key signs of Parkinson's disease are: tremor, slowness of movement, rigidity, and difficulty with balance.
Parkinson's disease affects both men and women in almost equal numbers. It shows no social, ethnic, economic or geographic boundaries. In the US, it is estimated that 60,000 new cases are diagnosed each year, joining the 1.5 million Americans who currently have Parkinson disease. While the condition usually develops after the age of 65, 15 per cent of those diagnosed are under 50.
Restless legs syndrome (RLS) is a sensorimotor disorder characterized by a distressing urge to move the legs and sometimes also other parts of the body, usually accompanied by a marked sense of discomfort or pain in the leg or other affected body part. RLS is triggered by rest or inactivity, and its symptoms are temporarily relieved by movement. It follows a circadian pattern, with symptoms most intense in the evening and nighttime hours.
According to the National Sleep Foundation's 1998 Sleep in America poll, 25 per cent of adults report experiencing unpleasant feelings in their legs a few nights a month or more, 15 per cent a few nights a week or more, and 8 per cent every night or almost every night. Of those who reported such RLS symptoms, 50 per cent said that the leg pain kept them from getting a good night's sleep.
Neurogen Corporation is a drug discovery and development company focusing on small molecule drugs to improve the lives of patients suffering from disorders with significant unmet medical need, including insomnia, Parkinson's disease and restless legs syndrome (RLS), pain, depression, and obesity. Neurogen conducts its research and development independently and, when advantageous, collaborates with world-class pharmaceutical companies to access additional resources and expertise.