Important Drug Approval for Parkinson Patients

May 12, 2016
Karen Appold

Nuplazid, which the FDA designated as a breakthrough therapy and granted priority review, could help approximately 50% of Parkinson patients.

Parkinson disease patients with associated psychosis now have a better option to treat hallucinations or delusions, which occur in approximately 50% of patients over the course of their disease. That’s because in April the U.S. Food and Drug Administration (FDA) approved Nuplazid (pimavanserin), a first-of-its-kind drug designed to treat psychosis due to Parkinson disease.

Previously, most drugs used to treat Parkinson disease psychosis blocked dopamine receptors, which are used to treat patients’ worsening motor skills.

“Once patients develop psychosis associated with Parkinson’s disease, many of them tend to not increase dopaminergic therapy due to the fear of worsening psychosis, so their motor skills symptoms-such as tremor, muscle rigidity, and difficulty with walking, continued to worsen,” explained Stuart Isaacson, MD, neurologist, Parkinson’s Disease and Movement Disorders Center, Boca Raton, FL.

Two antipsychotic drugs used to treat Parkinson that don’t interfere with the effectiveness of dopamine receptors have other disadvantages, Dr. Isaacson reports. Quetiapine (seroquel) lacks efficacy in Parkinson disease psychosis and has sedation as a common side effect, while Clozapine (clozaril) has efficacy but requires registry and weekly blood tests to monitor for low white blood cell counts, which occurs in 1% to 2% of patients.

How it works

Nuplazid targets 5-HT2A receptors, which are thought to play an important role in Parkinson disease psychosis. Nuplazid, which is in a new class of drugs called selective serotonin inverse agonists, avoids interfering with dopamine and other receptors commonly targeted by antipsychotics.

The FDA designated Acadia Pharmaceuticals Inc.’s Nuplazid as a breakthrough therapy, a program which expedites the development and review of drugs intended to treat a serious condition in which preliminary clinical evidence demonstrates substantial improvement over available therapy. The FDA also granted the drug priority review, which allows for the expedited review of a drug that offers a significant improvement over current medications.

The FDA’s approval of Nuplazid was based on data from the phase III study ACP-103-020 and other supportive studies, which represented the largest research and development program in Parkinson disease psychosis. In the study, Nuplazid significantly reduced the frequency and severity of psychotic symptoms compared to placebo on the Scale for Assessment of Positive Symptoms – Parkinson’s Disease.1 This benefit was achieved without impairing motor function.

“The achievement might equate to someone having a hallucination only once or twice a week compared to three times a day, or a child that was once happy and playful who became troublesome reverting to their previous behavior,” Dr. Isaacson said.

In trials, individuals with Parkinson were treated with typical medications used to address impaired motor skills. They had no interactions between those medications and Nuplazid. The most common adverse reactions (≥5% and twice the rate of placebo) were peripheral edema (7% Nuplazid vs. 3% placebo) and confusional state (6% Nuplazid vs. 3% placebo).1

Psychosis is associated with significant caregiver burden. “As the disease progresses, delusions become more prevalent,” Dr. Isaacson says. “Patients may falsely accuse family members of stealing money or a spouse of infidelity.”

Parkinson disease patients who experience hallucinations are two and a half times more likely to be admitted into a nursing home and are more likely to remain there permanently. Twenty-five percent of all hospitalizations of Parkinson disease patients are due to psychosis.

“The development of Nuplazid has opened up a new era to improve the lives of patients by not only treating their motor symptoms, but their non-motor symptoms as well,” Dr. Isaacson concluded.

Note: Dr. Isaacson was an investigator in phase 2 and phase 3 trials, is a co-author of the Lancet study, consulted with Acadia Pharmaceuticals Inc., and was involved in a regulatory presentation to the FDA.

1. Cummings J, et al. Pimavanserin for patients with Parkinson's disease psychosis: a randomised, placebo-controlled phase 3 trial. Lancet. 2014 Feb 8;383(9916):533-540.