The U.S. Food and Drug Administration has approved a once-a-day capsule formulation and a lower tablet strength for Nuplazid (pimavanserin), a treatment for the hallucinations and delusions associated with Parkinson’s psychosis.
The new formulation — a 34 mg capsule— enables patients to take the recommended oral dose once a day instead of the twice-daily existing 17-mg tablet dose.
Also approved was a 10 mg tablet (a lower-dose strength), for those Parkinson’s patients also being treated with cytochrome 3A4 inhibitors — such as some antibiotics, antidepressants and calcium channel blockers — that can affect how Nuplazid is metabolized.
“We are very pleased with the FDA approval of the Nuplazid 34 mg capsule and 10 mg tablet, underscoring Acadia’s continued dedication to advancing safe and effective treatment options for patients living with hallucinations and delusions associated with Parkinson’s disease psychosis,” said Steve Davis, the company’s president and CEO.
Nuplazid became the first FDA-approved treatment for hallucinations and delusions associated with Parkinson’s disease in April 2016, but the decision has been controversial.
A selective serotonin inverse agonist, Nuplazid works differently from other anti-psychotic medications in that it does not block dopamine — a brain neurotransmitter crucial to movement and motivation. Instead, it targets a subfamily of serotonin receptors (5 HT2A) of importance to cognition, memory, and the ability to learn.
Recent reports of studies into Nuplazid’s use in real-life settings have shown that the therapy is well-tolerated and can lead to clinical improvement in patients with Parkinson’s psychosis.
Joseph H. Friedman, MD, a Parkinson’s specialist at Butler Hospital and The Warren Alpert Medical School of Brown University, called Nuplazid “a significant advance in our treatments for the hallucinations and delusions in Parkinson’s” in the company release.
Friedman also welcomed the single 34 mg capsule as a “simpler and more straightforward” dosing regimen, important to patients like those he treats “who often also take multiple other medications concomitantly.”
Among the controversy surrounding Nuplazid is a CNN report claiming 244 possibly related patient deaths in the nine months after Nuplazid’s approval, citing an analysis by the Institute for Safe Medication Practices — a nonprofit healthcare group.
The FDA responded by stating that it would “continue to review the drug’s safety profile,” but adding that it recognized the medication’s “complex safety profile” and currently saw no reason to change the existing “black box” warning — the highest possible — placed on Nuplazid.
A recent editorial in The Lancet mentioned that safety concerns in Parkinson’s patients with psychosis were somewhat expected “because these patients are frail, and are usually in the end stages of the disease.” It called for more clinical trials into the medication.
In a related article published about the same time, three neurologists addressed reports of unusual risk linked to Nuplazid’s use, and some mentioned satisfaction with the medication among patients they treat using it while also recommending further study. Safety concerns need to be evaluated fully, “but in a scientific manner,” said Rajesh Pahwa, MD, a professor of neurology at the University of Kansas Medical Center in Kansas City.
Acadia is currently evaluating Nuplazid’s safety and efficacy in a wide range of people with dementia-related psychosis — including Parkinson’s patients — in the Phase 3 HARMONY trial (NCT03325556). This global study — testing pimavanserin at two doses, 34 mg and 20 mg, against placebo — is currently enrolling more than 350 dementia patients with psychosis at 80 sites across the U.S. and Europe. More information is available here.
All enrolled patients will be stabilized with 12 weeks of open-label pimavanserin treatment before being randomized into treatment and placebo groups.