People who see their loved ones stricken with Parkinson’s disease can be driven to desperate measures. They can become easy targets for a drug maker’s promises. They might even be driven to try a drug that has not been proven safe or effective.
While San Diego-based Acadia Pharmaceutical company defends its Parkinson’s drug (see below), many red flags appear to be flying around Nuplazid.
Nuplazid Fast Tracked to Market
Nuplazid’s safety review process was expedited by the FDA because Nuplazid had been designated as a “breakthrough therapy.” That meant Nuplazid demonstrated “substantial improvement” in patients with serious or life-threatening diseases compared to other treatments already on the legal drug market. Spurred by Big Pharma lobbying money, the U.S. Congress created the breakthrough designation in 2012 to speed the FDA’s approval process. Drug makers and their political friends in government have long criticized the FDA for being too slow in granting new drug approvals, though the agency is now, and has been for a long while, the fastest of its kind in the world. The FDA has granted some 200 drugs this new designation since 2012.
To recommend approval, an advisory committee first has to find a drug’s potential benefits outweigh its risks. Remember that word “potential,” which can be stretched an awful long way.
Since several people had said that their loved ones had been helped by Nuplazid, some FDA officials concluded Nuplazid’s public health benefit was enough to merit the drug’s approval. But others in the test trials said there was no way for them to know whether they were on Nuplazid or a placebo.
Dr. Paul Andreason, who led the FDA’s medical review, warned that patients taking Nuplazid during the company’s clinical trials suffered serious outcomes, including death, at more than double the rate of those taking the placebo. Dr. Andreason said the company’s limited testing had not convinced him Nuplazid’s benefits outweighed its risks.
The advisory committee voted 12-2 to recommend FDA approve Nuplazid for the treatment of Parkinson’s disease psychosis. The majority based their approval vote on a six-week study of about 200 patients. Dr. Andreason said three previous studies of Nuplazid had not shown it was effective, though they did show similar risk. The hearing transcript also showed that some committee members who voted for Nuplazid did so with reservations.
CNN noted that one physician stated he thought the risks were “going to be small” (and) “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.”
Another committee member said she wouldn’t have voted for Nuprazid’s FDA approval if there had been a safe and effective alternative on the market. A third pleaded to the FDA to “consider a large observational study” to ensure benefits would outweigh risks.
Nuplazid hit the open market in June 2016, and sales reached roughly $125 million in 2017.
Nuplazid Adverse Events Reports
Shortly after Nuplazid’s release, patients’ family members, doctors, and other healthcare workers began reporting “adverse events” possibly linked to the drug. Those “events” included deaths, life-threatening incidents, falls, insomnia, nausea, fatigue. In more than 1,000 reports, patients continued to experience hallucinations while on Nuplazid.
In November 2017, the Institute for Safe Medication Practices warned that 244 Nuplazid-linked deaths had been reported to the FDA between the drug’s launch and March 2017. ISMP also noted hundreds of reports suggested Nuplazid was “not providing the expected benefit” or was even potentially worsening the condition.
Tracked by the FDA, these so-called “adverse event reports” document deaths, side effects, and other issues. These reports can be made directly by consumers, caregivers and other medical professionals. Reports are submitted to either the FDA or to the drug maker, which is required to pass along any it receives to the federal government. Sometimes the person filing the report is convinced the side effects were caused by the drug. Sometimes the reporter ascribes no cause, but notes the patient was taking the drug.
An adverse event report does not mean the medication in question has been ruled as the cause of harm. The FDA uses the information to monitor potential issues with a drug and can take action as needed. The agency may update a drug’s label, restrict its use, pull it from the market, or suggest or demand some other action from the drug maker.
Nuplazid: More Harm than Good?
The ISMP concluded that Nuplazid reports “reinforces the concerns of those who warned that (Nuplazid) might do more harm than good.” A senior scientist for drug safety and policy for the nonprofit ISMP, Thomas Moore, said the deaths are an “important warning signal” that warrants further FDA review, and possible action.
Since ISMP released its analysis, FDA data shows reported deaths have risen to more than 700. As of June 2017, Nuplazid was the only medication listed as “suspect” in at least 500 of the death reports. Keep in mind that it’s also well known by drug and medical device safety experts that only 1-10 percent of actual adverse events are ever reported.
That’s a lot of potential Nuplazid-related deaths. Hindsight does tend to be 20-20, but physicians, medical researchers and other experts told CNN they worried that Nuplazid had been approved too quickly, based on too little evidence that it was safe or effective. Based on these mounting reports of deaths, they say more must be done to assess Nuplazid’s true risks.
Nuplazid’s maker, Acadia, has responded by saying, in part, that its “benefit/risk assessment of Nuplazid remains unchanged.” Acadia says it carefully monitors and regularly analyzes safety reports from both ongoing studies and adverse event reports. Acadia noted, for example, that since Nuplazid’s approval, two studies totaling more than 300 Alzheimer’s disease patients found no difference in the death numbers reported between Nuplazid and a placebo.
FDA commissioner Scott Gottlieb was asked by CNN’s Dr. Sanjay Gupta to give his thoughts on drugs that receive expedited reviews and then prompt concerns about safety once they become available. While Mr. Gottlieb refused to comment on a specific drug, he said he is “familiar with the circumstances” and that it’s important for FDA to balance safety with medical need. He also admitted this was a flexible standard and there may be more tolerance for risk when there is a significant need and patients don’t have an alternative.
Mr. Gottlieb may sound “reasonable,” but who is he kidding? There are always alternatives, unless one lives in a world where doing nothing at all – or simply praying– is not an alternative. Or one lives in a world where taking any path or action whatsoever that doesn’t involve swallowing a Big Pharma drug cannot be seen as an alternative.
Parkinson’s Drug Death Reports should alarm FDA
Time will tell, hopefully, and the truth will come out about whether or not any benefits Nuplazid may offer are worth its risks. We sincerely hope the FDA is paying attention for the sake of Nuplazid’s potential future victims, but also for the sake of the next 500 or more people who may be given a drug which has also not been sufficiently tested for safety and efficacy before being unleashed “on the market.” One can only wonder how many of the 200 drugs the FDA has granted “breakthrough therapy” status to since 2012 has been worthy of that designation. One thing seems certain right now: Whether Nuplazid is worthy of that status it was granted is highly debatable.