The drug is pimavanserin, manufactured by Acadia Pharmaceuticals and sold under the brand name Nuplazid.
Deemed a “novel drug” by the peer-review journal, Innovations in Clinical Neuroscience, it was approved for sale on April 29, 2016 as the first and only drug to treat patients experiencing hallucinations and delusions as a result of Parkinson’s disease, which are a fairly common manifestation of the disease in addition to the physical tremors for which it is best known.
The FDA reviewed the drug in only six-months, as opposed to the FDA’s standard ten-month review period. The six-month priority review is granted to outstanding cases in which clinical trials suggest the drug will provide “substantial improvement over available therapy on a clinically significant endpoint.”
As no other therapy existed to treat Parkinson’s related hallucinations and delusions, Nuplazid was approved to be the first to do so. One year after, the drug had reportedly been linked to 244 deaths. Today, the number has risen to over 700, according to the FDA.
So, how did Nuplazid get approved so quickly? And, why is it still on the market?
For starters, the disease it treats,Parkinson’s, affects approximately one million people in the United States alone. Out of these, almost half experience hallucinations or delusions as a result of the disease. The potential distress to patients and their loved ones is obvious.
In an investigation earlier this month, CNN reported that enthusiasm for the drug from family members and caregivers — many of whom thought the drug “transformed” loved ones’ experience with hallucinations or delusions in its clinical trials – were instrumental in getting Nuplazid on the FDA fast track.
In hindsight, however, the fast track appeared too fast to clearly determine if Nuplazid’s benefits outweighed its risks.
In a medical review conducted by the Institute for Safe Medication Practices’ (ISMP) scientific publication, QuarterWatch, in November 2017, it was revealed that Nuplazid’s approval was based on only one successful clinical trial—the fourth after three unsuccessful attempts in which only minimal benefits were recorded.
ISMP also noted that one of the FDA’s medical reviewers, Dr. Paul Andreason, opposed Nuplazid’s approval, expressing concerns that “in the case of pimavanserin, [the] treatment more than doubled the risk of death and/or serious adverse events in its pivotal trial.” His concerns fell on deaf ears—the drug was approved by a 12-2 vote.
According to CNN’s story on Nuplazid, Andreason has since left the FDA and was not surprised by the death reports that followed.
In response, Acadia Pharmaceuticals pointed to its company-patient support program and tight-knit relationship between consumers and health professionals — two institutions that foster an efficient reporting system of adverse events. Their argument is that the number of reports may not be as statistically significant as the news portrays it to be, since the system allows for such easy access.
Additionally, despite its quick approval, Acadia suggests patients may still need to wait for benefits. Acadia says these adverse events may have been reported before the patient endured four weeks of treatment — the expected timeline for the drug to become fully effective. What these matter of fact responses seem to avoid, however, is the main fact causing alarm – the number of deaths allegedly linked to Nuplazid.
Nuplazid is not the first drug fast tracked by the FDA to have potentially life-threatening side effects. Among many others, Vioxx, an anti-inflammatory drug marketed to relieve arthritis, was granted a six-month priority review because of its potential to produce significantly fewer gastrointestinal side effects than competitors.
It was approved by the FDA in May 1999 and removed from the market, worldwide, five years later. The reason? Vioxx was suspected of causing 27,000 heart attacks and deaths in it’s patients. The removal was initiated voluntarily by its manufacturer, Merck & Co., a global pharmaceutical company with headquarters in Kenilworth, N.J. (FDA). Merck paid over $4.85 billion in settlements for its former “blockbuster” drug.
The recall of Vioxx and other drugs that have proved to be ineffective or dangerous has raised skepticism not only of the drugs themselves, but of the manufacturers. In the words of one commenter referencing these cases: “perhaps the most terrifying aspect” is “the amount of time these drugs remained on the market without adequate warning to the consumers, after the manufacturers knew (or had reason to know) of either the dangerous risk or the general ineffectiveness of the drugs.”
Acadia Pharmaceuticals’ “Get-out-of-jail-free” card, it seems, is that the company placed a black box warning on the outside of Nuplazid’s packaging. Black box warnings are FDA-given labels for prescription drugs with serious and/or potentially deadly side effects. Merck did not place such a warning on Vioxx and consequently the use of black box warnings spiked after Vioxx was withdrawn from the market.
The black box on Nuplazid states: “Elderly patients with dementia-related psychosis treated with antipsychotics are at an increased risk of death compared to placebo.”
For now, the FDA and Acadia Pharmaceuticals have deemed the black box warning sufficient for Nuplazid to stay on the market.
Keeping Nuplazid on the market is indisputably good for one thing: Acadia Pharmaceutical’s stock price and revenue. The drug is Acadia’s only product, and it has single-handedly turned its maker into a multi-billion-dollar company.
Though Acadia suffered a slight loss in stock price when CNN first broke the story on the Nuplazid-related deaths, the company’s current market capitalization (how much the company is worth), is $2.5 billion. Some analysts estimate that annual revenue from Nuplazid will hit $1 billion, and that’s only from the Parkinson’s applications; the company reports having other applications in the works.
Suffice to say that Nuplazid has been a blockbuster for Acadia. What remains far from clear, however, is how safe the drug is for patients.
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