Nuplazid was approved by the U.S. Food and Drug Administration (FDA) in 2016 in an expedited approval process – one that is granted to breakthrough therapies that demonstrate substantial improvement in patients with serious or life-threatening conditions.1 Manufactured by Acadia, Nuplazid is a treatment for the hallucinations and delusions associated with Parkinson’s disease psychosis.2 New concerns are being raised about serious side effects, including several deaths, that have many questioning the risks versus the benefits of this treatment.1
Nuplazid is the first (and currently only) treatment approved for the psychosis which can affect up to 50% of those with Parkinson’s disease (PD). Prior to its approval, doctors had limited choices on how to treat their patients suffering from the hallucinations and delusions. Hallucinations are when patients see, hear, or experience things that are not real, and delusions are when patients believe things that aren’t based in reality. Hallucinations and delusions can be frightening and frustrating for those with PD and their caregivers, and they greatly decrease the quality of life for those who suffer from them.2
About the approval process
Several family members of loved ones with PD spoke to the FDA advisory committee and pleaded for Nuplazid’s approval, believing it could provide an end to their loved ones’ suffering. And while the FDA did approve the drug for marketing, some are questioning whether the clinical trial data was sufficient to prove efficacy and safety of Nuplazid.1
The pivotal clinical trial to prove Nuplazid’s efficacy was a 6-week trial involving 199 patients who had hallucinations and/or delusions related to PD. The patients were randomly selected to receive either Nuplazid or a placebo (an inert substance). Those who received Nuplazid showed a greater decrease in the frequency and severity of their hallucinations and/or delusions compared to those receiving placebo.2
Critics have noted that the scale used to determine the benefit was adapted to specifically measure the sorts of hallucinations and delusions that are experienced by those with PD-related psychosis. The modified scale hasn’t been used in other trials, leading some to question whether the scale is valid.3
During the approval process, the physician who led the FDA’s medical review – Dr. Paul Andreason – raised concerns that patients who received Nuplazid in clinical trials experienced double the rate of serious side effects, including death. Dr. Andreason also noted that two earlier clinical trials had failed to show the drug was effective, although the side effects were seen in all the trials. However, the FDA committee voted in favor of approval, hoping that the benefits for patients would outweigh the risks.1
Safety concerns over numerous serious side effects
After the drug hit the market in June 2016, sales climbed – and so did adverse event reports. Adverse events are what the FDA calls “any undesirable experience associated with a medical product,” and healthcare professionals are required to report serious adverse events, including death, life-threatening events, hospitalization, disability or other serious medical events, to the FDA. Consumers and caregivers can also report adverse events directly to the FDA or to the drug manufacturer.1,4
In November 2017, the Institute for Safe Medication Practices released an analysis that warned 244 deaths had been reported to the FDA between June 2016 and March 2017, as well as hundreds of reports of Nuplazid not being effective.5 The FDA’s data currently shows the number of deaths potentially linked to Nuplazid is now over 700.6 However, Nuplazid hasn’t been causally linked in all these cases, and it’s worth remembering that most of the patients who suffer from PD-related psychosis are at advanced stages of PD and are already at a high risk of death.1
What does this mean for current patients?
As of now, the FDA has not issued additional warnings or moved to pull Nuplazid from the market. Nuplazid does have a black-box warning – the strongest warning from the FDA – regarding the increased risk of death in elderly patients. Each individual patient should fully discuss the risks and benefits with their doctor.
Ellis B, Hicken M. FDA worried drug was risky; now reports of deaths spark concern. CNN. Available at https://www.cnn.com/2018/04/09/health/parkinsons-drug-nuplazid-invs/index.html. Accessed 4/12/18.
Nuplazid prescribing information. Available at https://www.nuplazid.com/pdf/NUPLAZID_Prescribing_Information.pdf. Accessed 4/12/18.
Tedeschi B. New Parkinson’s drug could reduce hallucinations, but at what cost? STAT. Available at https://www.statnews.com/2016/03/28/parkinsons-psychosis-nuplazid/. Accessed 4/12/18.
What is a serious adverse event? U.S. Food & Drug Administration. Available at https://www.fda.gov/Safety/MedWatch/HowToReport/ucm053087.htm. Accessed 4/12/18.
Safety Signals for Two Novel Drugs. Institute for Safe Medication Practices. Available at https://www.ismp.org/sites/default/files/attachments/2018-01/2017Q1_0.pdf. Accessed 4/12/18.
FDA Adverse Events Reporting System Public Dashboard. Available at https://fis.fda.gov/sense/app/777e9f4d-0cf8-448e-8068-f564c31baa25/sheet/45beeb74-30ab-46be-8267-5756582633b4/state/analysis. Accessed 4/12/18.