FDA approves first drug for Parkinson disease psychosis

Although dopamine replacement strategies can alleviate the motor symptoms of Parkinson disease, patients have had few therapeutic options for non-motor symptoms, which include depression, dementia, sleep abnormalities and autonomic failure. Now the FDA has approved Acadia Pharmaceuticals' pimavanserin as the first drug to treat hallucinations and delusions associated with psychosis in Parkinson disease, which affect up to 50% of patients during the course of their illness.

Pimavanserin, a serotonin (5-hydroxytryptamine) receptor 2A (5-HT_2A) inverse agonist, failed in its first three randomized and controlled trials, showing no improvement on the primary end point of the Scale for the Assessment of Positive Symptoms (SAPS), a scale that was designed for schizophrenia. The developers refined the end point before launching a fourth trial, focusing the scale on the items of most clinical relevance for Parkinson disease. This trial showed that the drug decreases the frequency and/or severity of hallucinations and delusions without worsening the primary motor symptoms of Parkinson disease. In March, the FDA's panel of independent psychopharmacological drug experts voted 12 to 2 in favour of approval, although many of the experts said that the drug's efficacy was only modest. The most common side effects include swelling, nausea and confusion.

Analysts forecast that annual global sales for pimavanserin could hit US$2.8 billion by 2021, shows data from Thomson Reuters Cortellis.

Other experimental drugs aimed at non-motor aspects of Parkinson disease include Biotie Therapies' SYN-120, a dual 5-HT₆ and 5-HT_2A antagonist, which is in Phase IIa trials for cognitive dysfunction associated with Parkinson disease.

Two adenosine A_2A receptor inhibitors, Biotie's tozadenant and Kyowa Hakko Kirin Co.'s istradefylline, are in Phase III trials for their potential to treat both motor and non-motor aspects of the degenerative disease. However, Merck & Co. previously made it to Phase III trials with its adenosine A_2A receptor antagonist preladenant, but failed to generate evidence of efficacy.