In 2016, a cadre of family members stood in front of the U.S. Food and Drug Administration to urge the agency to approve a new drug called Nuplazid that could help those suffering from psychosis associated with Parkinson’s disease.
Within two years of the FDA approving the drug for use in patients with Parkinson’s disease, Nuplazid was connected with more than 700 reports of deaths.
The antipsychotic drug was approved under the FDA’s Breakthrough Therapy designation, which allows a drug to be approved in expedited fashion if it shows substantial improvement over existing therapies.
However, the increasing number of deaths and weak evidence suggests that the benefits of Nuplazid do not outweigh the risks. Now, scientists are wondering whether Nuplazid should be taken at all while those whose family members died while taking the drug start exploring the possibility of lawsuits.
What is Nuplazid?
Nuplazid is the brand name for a drug called pimavanserin. Pimavanserin was developed by biopharmaceutical company Acadia Pharmaceuticals.
Nuplazid was the first and is currently the only drug approved by the FDA to treat hallucinations and delusions associated with psychosis experienced by some who have Parkinson’s disease.
According to the official prescribing information sheet for Nuplazid, it is unclear just how pimavanserin treats hallucinations and delusions1.
“However, the effect of pimavanserin could be mediated through a combination of inverse agonist and antagonist activity at serotonin 5-HT2A receptors and to a lesser extent at serotonin 5-HT2C receptors,” the sheet says.
The recommended dose of Nuplazid is 34 mg taken once a day in a capsule with or without food. This new formulation was approved by the FDA in June 2018. Previously, the recommended dose was a 17 mg tablet taken twice a day.
When taking Nuplazid at the same time as strong CYP3A4 inhibitors, the recommended dose is 10 mg.
The move to a tablet taken once a day allowed patients to reduce the number of pills taken each day.
“The replacement of two 17 mg tablets with a single 34 mg capsule provides a simpler and more straightforward approach for the 34 mg once daily Nuplazid dosing regimen, while also reducing the overall pill burden for my Parkinson’s disease patients who often also take multiple other medications concomitantly,” Dr. Joseph H. Friedman of Butler Hospital and Warren Alpert Medical School of Brown University said in a press release2.
Nuplazid Side Effects
The most common side effects associated with Nuplazid are peripheral edema and confusional state. Peripheral edema is swelling of the lower legs or hands. Symptoms can include swelling, pitting, stiffness, heaviness, increased weight, or discoloration.
Like many other types of antipsychotic drugs, Nuplazid carries a black box warning — the most severe warning on a drug’s label — about the risk of death.
“Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death,” the warning reads1. “NUPLAZID is not approved for the treatment of patients with dementia-related psychosis unrelated to the hallucinations and delusions associated with Parkinson’s disease psychosis.”
Early History of Nuplazid
Development of Nuplazid started back in the 1990s. Scientists at Acadia first began a project to find 5-HT2A inverse agonists in 19993. By 2001, pimavanserin was first synthesized by an Acadia chemist working in Denmark.
In late 2014, the FDA granted Nuplazid Breakthrough Therapy designation to treat Parkinson’s disease psychosis.
“The Breakthrough Therapy designation for Nuplazid reinforces the urgent need for a treatment for patients with Parkinson’s disease psychosis,” Dr. Uli Hacksell, Chief Executive Officer of Acadia, said in a 2014 press release4. “Nuplazid represents a potential new class of psychosis medication and could be the first drug approved in the United States for patients with Parkinson’s disease psychosis.”
Breakthrough Therapy designation is a relatively recent expedition process by the FDA that expedites the development and review of a drug that treats severe conditions5. Preliminary evidence must show that the drug demonstrates “substantial improvement” over existing therapies.
Congress created the designation in 2012 as part of the Food and Drug Administration Safety and Innovation Act to speed up the slow approval process. According to one 2016 article, the average time from application to approval by the FDA for drugs is 12 years6.
An estimated 200 drugs have been granted Breakthrough Therapy designation since it was first created.
Nuplazid Officially Approved in 2016
Despite being given Breakthrough Therapy designation in 2014, an advisory committee at the FDA still had to find the benefits of the drug outweighed the risks.
During the review, family members of Parkinson’s disease sufferers pleaded with the agency to approve the drug. In an investigative report on Nuplazid, CNN spoke with one of the people who spoke to the advisory committee7.
“I have two young children who love their grandmother,” he told the committee, according to CNN. “If nothing is done to bring her back to some semblance of normalcy, my children will never remember their grandmother for who she is: a loving, funny, caring woman who has improved the lives of all of the loved ones who surround her. Please, I beg you, do not deprive my children and their grandmother of experiencing that love.”
In a 12 to 2 vote, the committee recommended Nuplazid for approval to treat Parkinson’s disease psychosis in 2016.
Because as many as 50 percent of patients with Parkinson’s disease will experience hallucinations or delusions at some point in their illness and there are few drugs to treat it, the approval was hailed as a victory for patients with the degenerative disorder.
“Hallucinations and delusions can be profoundly disturbing and disabling,” Mitchell Mathis, director of the Division of Psychiatry Products in the FDA’s Center for Drug Evaluation and Research, said about the approval8. “Nuplazid represents an important treatment for people with Parkinson’s disease who experience these symptoms.”
A six-week clinical trial that showed Nuplazid had been superior to placebo in decreasing Parkinson’s disease psychosis without worsening the disease helped the committee approve the drug.
Over 700 Deaths Tied to Nuplazid
It didn’t take long for desperate family members to start getting loved ones on Nuplazid. Within a year of hitting the market, sales of Nuplazid rose to about $125 million in 2017.
However, shortly after hitting the market, reports from across the country began coming in about how patients taking Nuplazid were dying. In a November 2017 report from the Institute for Safe Medication Practices, the group reported that the FDA received more than 2,000 adverse reports between the drug’s launch and March 20179.
Of those 2,236 reports, 244 reports involved deaths.
The reports are made to the agency through the FDA Adverse Event Reporting System (FAERS), which allows patients, caregivers, family members, and medical professionals to report side effects associated with drugs. Because the system is voluntary, it’s likely that many cases of death have gone unreported.
The number of deaths associated with Nuplazid reported to the FDA has risen to more than 700 since that analysis.
Although the reports that those taking Nuplazid died don’t necessarily mean the drug was the cause of the death, it reinforces the belief by many physicians that the drug had been approved too quickly and may not be as safe or effective as Acadia claimed.
“This is almost unheard of, to have this many deaths reported,” Diana Zuckerman, founder, and president of the nonprofit think tank the National Center for Health Research, told CNN in April 20187. “You just don’t see this with most new drugs — you don’t see all these reports — so you have to take it seriously.”
Acadia and FDA Downplay Nuplazid Deaths
After CNN published its investigative piece, Acadia responded to the claims that Nuplazid caused an unacceptable number of deaths.
Acadia argued that patients suffering from Parkinson’s disease psychosis are already at a higher risk of death. The pharmaceutical company also said that Nuplazid is distributed through specialty pharmacies, so there are likely going to be more reports than other antipsychotic drugs that are distributed through retail stores.
The FDA similarly noted that the deaths involved elderly patients in advanced stages of Parkinson’s disease who are likely taking other medications as well.
“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 told CNN in a statement.
Family Members Exploring Nuplazid Lawsuits
Although the drug has only been on the market a few years, it has already been linked to hundreds of deaths with potentially hundreds more incoming. Family members of those who died while taking Nuplazid are exploring the possibility of a lawsuit against Acadia.
Some evidence suggests that not only is Nuplazid associated with a significantly higher risk of death but it may also be ineffective in treating Parkinson’s disease psychosis.
Those who have lost loved ones while taking Nuplazid should contact a qualified attorney to learn more about how a lawsuit can help.