Thank you for the opportunity to speak today. My name is Dr. Stephanie Fox-Rawlings. I was previously a neuroscientist at Children’s National Medical Center and now am a Senior Fellow at the National Center for Health Research. Our research center analyzes scientific and medical data to provide objective health information to patients, providers and policy makers. We do not accept funding from the drug or medical device industry. I have no conflict of interest.
We strongly support efforts to find safe and effective treatments for patients with Parkinson’s Disease, so patients can live as independently as possible. Reducing psychotic symptoms is very important, but not when the risk for harm outweighs the potential benefit.
We understand that psychotic symptoms are upsetting and debilitating. The question is, if a drug needs to be taken for the rest of one’s life, and the drug can shorten one’s life, then how much benefit is required for FDA approval?
The data presented today suggests that pimavanserin [Nuplazid] provides a statistical improvement in symptoms. However, the average improvement of 3 points or 23% on the SAPS-PD scale does not appear to be clinically meaningful. It is also concerning that the SAPS-PD scale may not test the appropriate types of hallucinations and delusions. The scale is a shortened version of a scale for schizophrenia, thus it focuses on the types of hallucinations and delusions most prevalent with schizophrenia. But these are not most common with PDP [psychosis associated with Parkinson’s Disease]. The scale may give undo weight to the less common hallucinations like auditory hallucinations, and it does not include related symptoms such as illusions.
If the drug produced modest benefits with few side effects, it could still be useful to patients. However, during the 6 week trials, ~10% of patients taking the drug had a severe adverse event, about 2x that of patients taking placebo. This included 3 patients who died taking the 34mg dose as opposed to 1 taking placebo. Other adverse events included psychiatric and nervous system disorders, suicidal thoughts, and confusion.
Furthermore, patients are expected to be treated for years. Without longer placebo controlled studies, we cannot predict whether the treatment will provide long term benefit or if longer exposure will affect the rate of serious adverse events. The pivotal study cannot address these questions. The sponsors provided data from a long-term open label study, but we cannot determine relevance without a comparison group.
Another issue is that the drug does not statistically improve psychotic symptoms for non-whites, females, or patients <65 years or >75 years. However, small numbers for some of these groups make this data difficult to interpret.
The drug may be beneficial for a subpopulation of patients with PDP such as those with specific types of psychosis or within a specific age range. However, the current data does not provide enough information to determine if the benefits greatly outweigh the risks for any subgroup.
In conclusion, because of concerns over the limited efficacy, the test used, and the high incidence of adverse events, we urge you to not support the approval of pimavanserin. Thank you for your time and consideration of our views.
Pimavanserin was approved in 2016 under the name Nuplazid. In 2018, concerns arose from the large number of adverse events reported to the FDA related to lack of effect, worsening symptoms, or death. See this article for more detail.