In the United States alone, about 50,000 people are diagnosed with Parkinson’s disease every year. Of the estimated one million Americans who have the degenerative disorder, roughly half will experience hallucinations or delusions associated with Parkinson’s disease.
The effects of Parkinson’s disease psychosis can be disturbing and debilitating for both patients and family members. That’s why countless people were so excited and hopeful when antipsychotic drug Nuplazid was approved by the U.S. Food and Drug Administration in 2016 to treat hallucinations and delusions in patients with Parkinson’s disease.
Unfortunately, shortly after the drug’s approval, the FDA started receiving thousands of reports of adverse effects, including more than 700 deaths associated with Nuplazid.
Learn more about how the drug was approved and why family members of those taking Nuplazid are considering lawsuits against drugmaker Acadia Pharmaceuticals.
Developed and manufactured by Acadia Pharmaceuticals, Nuplazid is an antipsychotic drug used to treat hallucinations and delusions.
Nuplazid contains the active ingredient pimavanserin, which works differently than other atypical antipsychotic drugs on the market.
Pimavanserin is an “antagonist at serotonin 5-HT2A receptor, with a novel mechanism that allows it to behave as a selective inverse agonist of the receptor without significant affinity or activity at dopamine receptors — contrary to the mechanism of other receptors,” according to MD Magazine, a clinical news site for physicians.
The exact mechanism of action remains unclear, according to the official prescribing sheet of Nuplazid. However, it is unique from other antipsychotic drugs in that it doesn’t affect dopamine receptors, which could worsen the motor symptoms in Parkinson’s disease.
When Nuplazid was first released, it was only available in 17 mg tablets to be taken twice a day with or without food.
However, in June 2018, the FDA approved a 34 mg capsule and a 10 mg capsule of Nuplazid.
“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,” Steve Davis, Acadia’s President and Chief Executive Officer, said in a press release at the time.
The introduction of a 34 mg capsule allows a patient to take a single pill once a day, which is particularly convenient for patients with Parkinson’s disease who often taken multiple other drugs at the same time.
For those taking strong CYP3A4 inhibitors like ketoconazole at the same time as Nuplazid, the recommended dose is one 10 mg tablet taken once a day. CYP3A4 inhibitors can inhibit the metabolism of Nuplazid.
Nuplazid was approved by the FDA in April 2016. However, the antipsychotic drug took a controversial road to get there.
The roots of the drug date back to 1993 when a professor at the University of Vermont founded Receptor Technologies. Four years later, that company changed its name to Acadia Pharmaceuticals, and within two years, scientists at the company started looking to discover antipsychotic agents selectively acting as 5-HT2A inverse agonists. By 2001, an Acadia chemist had synthesized pimavanserin.
After undergoing several phases of research and studies, Acadia applied for the designation of Breakthrough Therapy. This is a recent designation introduced by the Food and Drug Administration Safety and Innovation Act in 2012 to speed up the approval process of certain drugs.
“Breakthrough Therapy designation is a process designed to expedite the development and review of drugs that are intended to treat a serious condition and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over the available therapy on a clinically significant endpoint(s),” according to the FDA.
In September 2014, the FDA granted Nuplazid Breakthrough Therapy designation.
Some members of the medical community praised the decision of the FDA because of Nuplazid’s promise in treating such devastating symptoms.
“The hallucinations and delusions in Parkinson’s disease psychosis are devastating to patients and contribute to a dramatic rise in caregiver burden,” Joyce Oberdorf, President and Chief Executive Officer of the National Parkinson Foundation, said in a press release. “Parkinson’s disease psychosis is a leading cause of nursing home placement for Parkinson’s patients and, with no FDA-approved therapy for this serious condition, there is a great unmet medical need for an effective, safe, and well-tolerated treatment option for patients.”
Although given Breakthrough Therapy designation, Nuplazid still had to be approved by an FDA advisory committee.
The committee considered results of a six-week clinical trial of 199 patients, which showed that Nuplazid was better at treating hallucinations and delusions without negatively affecting the motor symptoms of Parkinson’s disease.
While the results looked promising, not everyone was sold. Dr. Paul Andreason, who led the FDA’s medical review of the drug, warned that the testing was limited and people died at more than double the rate of those taking a placebo, according to a CNN investigative report.
In fact, three earlier studies did not show the drug was effective but had a similar risk of death. He recommended against approving the drug.
But, urged by family members of those suffering from Parkinson’s disease without much hope, the panel voted 12-2 in favor of approval.
CNN reported that one committee member voted in favor of approval but still had reservations.
“I guess I’m hoping that the risks are going to be small, and I think the benefits for some of these people who are very sick and whose families are affected by this, I think they’re probably willing to take that risk,” the physician said at the hearing.
Side effects were reported in clinical trials, but the most common ones were mostly mild.
“In clinical trials, the most common side effects reported by participants taking Nuplazid were: swelling, usually of the ankles, legs, and feet due to the accumulation of excessive fluid in the tissue (peripheral edema); nausea; an abnormal state of mind (confused state),” according to the FDA.
Not long after approval, the FDA started receiving thousands of reports of side effects through its voluntary reporting system. From the release of the drug to March 2017, the Institute for Safe Medication Practices (ISMP) noted that the FDA received 2,236 reports of adverse effects. Nearly 500 reports were for hallucinations, 333 were for ineffectiveness, and 258 were for a confusional state.
Most notably, 244 reports involved death.
The November 2017 analysis from ISMP put the concerns about Nuplazid on the forefront. By April 2018, CNN had published a lengthy investigative piece that put the number of deaths associated with Nuplazid at more than 700.
Even though Nuplazid carries a black box warning about the risk of death, physicians began expressing concerns that the number of deaths from Nuplazid was unacceptably high.
“This is almost unheard of, to have this many deaths reported,” Diana Zuckerman, founder, and president of the National Center for Health Research, told CNN. “You just don’t see this with most new drugs—you don’t see all these reports—so you have to take it seriously.”
In light of the numerous reports, Acadia stood behind its drug.
The pharmaceutical company claimed that Nuplazid is often given to patients in the advanced stages of Parkinson’s disease, patients who are already at a higher risk of death. It also said that the number of deaths is likely on par with other antipsychotic drugs, only those who distribute Nuplazid report them more often.
The FDA has yet to take action against Nuplazid. The agency told CNN that Nuplazid has a complex safety profile and carries several warnings about the risks.
“Based on these data, the FDA has, at this time, not identified a specific safety issue that is not already adequately described in the product labeling,” the agency said to the news outlet.
Nuplazid is being considered for expanded use in the treatment of dementia-related psychosis. Nuplazid was again given Breakthrough Therapy designation in October 2017 for the treatment of dementia patients.
Drugs that are plagued by higher than expected side effects, including those as severe as death and ineffectiveness, are often the center of lawsuits from patients and loved ones.
Lawyers around the country are expecting the same with Nuplazid.
Family members of loved ones who died while taking Nuplazid may be entitled to compensation if Acadia failed to test the drug adequately or concealed the risks from patients and medical professionals.
With the drug still being given to patients with Parkinson’s disease and potentially reaching a broader market soon, lawyers anticipate a rise in the number of deaths associated with Nuplazid. Those who have lost loved ones to Nuplazid should contact an attorney to find out more about filing a lawsuit.
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