The Food and Drug Administration says it is re-examining the safety of a medication that was approved despite concerns that not enough was known about the drug's risks.
In response to questioning at a budget hearing last week, FDA Commissioner Scott Gottlieb told members of Congress that he would "take another look" at Nuplazid, which is the only drug approved to treat hallucinations and delusions associated with Parkinson's disease psychosis.
The medication has been cited as a so-called "suspect" medication in hundreds of deaths voluntarily reported by caregivers, doctors and other medical professionals since it hit the market, as highlighted in a recent CNN report.
The FDA told CNN this week that the agency had already begun conducting a new evaluation of the medication when Gottlieb was questioned about it at the hearing. The agency said the review had started several weeks ago.
"What does it take for a drug like this to be taken off the market?" asked US Rep. Rosa DeLauro, a member and former chair of the congressional subcommittee responsible for funding and overseeing the FDA.
DeLauro pressed Gottlieb for answers on his agency's response to the safety concerns surrounding Nuplazid.
"How many more adverse events do we have to have reported? How many people, quite frankly, have to die? Why does the industry always take precedence over public health and safety?"
Tracked by the FDA, the adverse event reports cited by DeLauro do not mean that a suspected medication has been ruled the cause of harm and are typically not the result of official investigations. But the FDA uses the information to monitor potential issues with a drug and can take action as needed: updating a medication's label, for instance, or restricting its use. In rare cases, the agency can even pull a drug off the market.
When asked by CNN about what prompted the FDA's new evaluation of Nuplazid, the agency said the decision was based on a number of factors but wouldn't say what those factors were. Instead, it would only comment generally, saying that it identifies "potential signals of serious risk/new safety information" in part by using adverse event data and that the agency is not suggesting physicians stop prescribing the drug or take patients off of it while a safety evaluation is taking place.
The FDA has noted that the death reports citing Nuplazid have typically involved elderly patients with advanced-stage Parkinson's disease who suffered from numerous medical conditions and often take other medications that can increase the risk of death.
But physicians, researchers and other medical experts told CNN that the high number of reports deserved a closer look to determine whether they were related to the drug. They also recommended further testing of Nuplazid, worrying that the drug had been approved too quickly, based on too little evidence that it was safe or effective.
Nuplazid's review was expedited by the FDA because it had been designated a "breakthrough therapy," meaning it demonstrated "substantial improvement" in patients with serious or life-threatening diseases compared to treatments already on the market.
Dr. Paul Andreason, the physician who led the FDA's medical review of Nuplazid, warned that patients taking the drug during the company's clinical trials experienced serious outcomes, including death, at more than double the rate of those taking the placebo. But the FDA ruled that the potential benefits outweighed the risks, agreeing with an advisory committee that cited a lack of safe alternatives and the pleas from family members who claimed the drug was already helping or could help their loved ones.
At that advisory committee meeting two years ago, one woman said that her grandmother had been part of the clinical trials for the drug and that Nuplazid had been life-changing.
"We didn't know what to expect or even if she was on the drug" or a placebo, said Zoey Wade. "We soon realized that she must be taking the drug, because she really returned to herself. Her hallucinations reduced, and she better understood what was real and what was imaginary."
Shortly after Nuplazid's release, however, patients' family members, doctors and other health care professionals started reporting "adverse events" possibly linked to the medication -- including deaths, life-threatening incidents, falls, insomnia, nausea and fatigue.
During the first 10 months Nuplazid was on the market, 244 deaths were reported to the FDA in which Nuplazid was a "suspect" medication, according to an analysis conducted by the Institute for Safe Medication Practices. FDA data now show that the number of reported deaths has risen to more than 700. In more than 1,000 reports, patients continued to experience hallucinations while on Nuplazid.
After CNN published its investigation on Nuplazid, reporters were contacted by family members who said the drug helped tame hallucinations with few apparent side effects and others who said they believe Nuplazid contributed to their family member's decline or death. Some said they had not yet reported these experiences to the drugmaker or the FDA.
While the FDA has long been criticized for being too slow to approve drugs, DeLauro seized on its push to streamline the process, lambasting the agency for putting industry interests and efficiency above public health and safety.
DeLauro described the number of adverse events and deaths as "staggering" and "unprecedented." She also expressed concern that the drugmaker, Acadia Pharmaceuticals, is attempting to get the drug approved for a larger population: patients who suffer from dementia-related psychosis.
"I don't know why it should stay on the market, especially when the FDA has not determined it to be safe and while the number of adverse events continues to soar," she told Gottlieb.
In response to the congresswoman's remarks, Acadia told CNN that adverse event data alone are "not a comprehensive and accurate indicator of the safety profile of any drug." In response to CNN's earlier report on the drug, Acadia said there are a number of reasons for the higher volume of death reports, including the fact that the company distributes Nuplazid through a network of specialty pharmacies that puts the company in more frequent contact with both patients and caregivers -- meaning Acadia is more likely to receive reports of death, which it is required to pass along to the FDA.
Commissioner Gottlieb told the committee that the FDA is careful about the decisions it makes and that there may be a higher tolerance for risk in situations where there is an unmet medical need, "so long as the patient is properly informed of what those risks are." This echoed what he told CNN's Dr. Sanjay Gupta in an interview earlier this month.
The FDA previously told CNN that it was aware of Nuplazid's "complex safety profile" at the time of approval and required the drugmaker to place warnings on its labeling. The agency also said that, though it was continuing to monitor available information about Nuplazid, it had "not identified a specific safety issue" not already reflected on the medication's label.
DeLauro's office told CNN that it plans to follow up with the FDA about its inquiry into Nuplazid.