FDA’s Opioids Adviser Accuses Agency Of Having ‘Direct’ Link To Crisis

The Guardian Article Here

The Food and Drug Administration is sacrificing American lives by continuing to approve new high-strength opioid painkillers, and manipulating the process in favor of big pharma, according to the chair of the agency’s own opioid advisory committee.

Dr Raeford Brown told the Guardian there is “a war” within the FDA as officials in charge of opioid policy have “failed to learn the lessons” of the epidemic that has killed hundreds of thousands of people over the past 20 years and continues to claim about 150 lives a day.

Brown accused the agency of putting the interests of narcotics manufacturers ahead of public health, most recently by approving a “terrible drug”, Dsuvia, in a process he alleged was manipulated.

“They should stop considering any new opioid evaluation,” said Brown. “For every day and every week and every month that the FDA don’t do the right thing, people drop dead on the streets. What they do has a direct impact on the mortality rate from opioids in this country.”

Brown, an anesthesiologist who chairs the FDA committee of specialists advising the agency on whether to approve new opioid painkillers, said he no longer had confidence in repeated assurances by the FDA leadership that it was taking the epidemic seriously and prepared to put public health above the commercial interests of drug makers.

“I think that the FDA has learned nothing. The modus operandi of the agency is that they talk a good game and then nothing happens. Working directly with the agency for the last five years, as I sit and listen to them in meetings, all I can think about is the clock ticking and how many people are dying every moment that they’re not doing anything,” he said. “The lack of insight that continues to be exhibited by the agency is in many ways a willful blindness that borders on the criminal.”

Brown’s comments echo criticisms by US senators who have condemned the FDA for what they say is its “complicity” in the epidemic, for approving the powerful painkillers that drove the crisis and then failing to use its powers to protect the public as the death toll escalated.

Four US senators wrote to the head of the FDA, Dr Scott Gottlieb, late last year urging him not to allow Dsuvia, a powerful opioid pill, on to the market because it was “to the detriment of public health”.

Dsuvia is a branded narcotic sufentanil pill, a more potent version of fentanyl, made by Californian pharmaceutical company AcelRx. The signatories included Senator Joe Manchin of West Virginia, whose state has the highest rate of opioid overdose deaths in the country.

“This puzzling and unacceptable course of events is unfortunately reminiscent of previous FDA processes and practices that contributed to the opioid epidemic,” the letter said.

The FDA’s credibility has been badly damaged by the opioid crisis amid accusations that at times it behaved less as a regulator overseeing the pharmaceutical industry than a business partner of drug manufacturers. The agency helped unleash the epidemic two decades ago when it approved the sale of a high strength narcotic pill, OxyContin, as safer and more effective than other painkillers on the say so of the manufacturer, Purdue Pharma, and without requiring clinical trials. Since then the FDA has approved other opioids for wide prescribing even as evidence mounted the drugs were addictive, open to abuse and often not effective for long-term use.

The FDA was also embarrassed by revelations that officials responsible for opioid approvals were taking part in “pay to play” schemes in which manufacturers paid to attend meetings to draw up the criteria for approving prescription narcotics.

Donald Trump’s opioid commission identified the failure of the FDA and other federal institutions to properly regulate opioids and their manufacturers as an important factor in the epidemic.

After Trump appointed Gottlieb, the new FDA chief admitted the agency “didn’t get ahead” of the crisis and promised “dramatic” action. He said he favoured examining not only whether an opioid worked but whether it was needed and whether the risks of it feeding the epidemic outweighed benefits for patients.

But that commitment has been called into question by the slow pace of introducing new practices and regulations – and by the approval of Dsuvia, a potent pill developed with the US defense department.

An advisory committee rejected the drug in 2017 over safety concerns. The senators said that they were “deeply troubled” that when Dsuvia was resubmitted for consideration the following year, the FDA excluded members of the agency’s drug safety committee from the hearing. The senators also said they were concerned because the decision was made when Brown, a strong critic of Dsuvia, was absent at a professional conference in San Francisco.

“There’s no question in my mind right that they did that on purpose,” he said. “The FDA has a lack of transparency. They use the advisory committees as cover.”

The FDA is not required to follow the decisions of its advisory committees but has been wary of going against their decisions since 2012, when the agency created a political storm by overruling a decision to reject Zohydro, an opioid 10 times more powerful than regular painkillers.

Doctors and specialists on the committee questioned the safety of the drug and the need for it given the epidemic. The senior FDA official at the hearing, Dr Bob Rappaport, who was head of the agency’s opioid approval division, angered other members by telling them there had to be “a level playing field for business”, which was widely interpreted as putting the right of pharmaceutical companies to make money ahead of public health.

Brown described a breakdown in confidence and trust between his advisory committee and FDA officials responsible for opioid approvals. He characterized them as out of touch with the consequences of the epidemic and locked into a view promoted by drugmakers that those who become hooked are to blame for their addiction not the pills or prescribing practices.

Brown blamed the problem in part on “cozy, cozy relationships between the pharmaceutical industry and various parts of the FDA”. Since a change to the FDA’s funding in the 1990s, the agency division responsible for opioid approvals relies on the drug industry for 75% of its budget. The agency denies the money buys influence.

The FDA declined to respond to Brown’s specific criticisms.

Gottlieb has previously defended Dsuvia by saying it is required for use in circumstances where other drugs cannot be administered, such as a battlefield. The FDA chief promised “very tight restrictions” on its distribution to stop the drug appearing on the illicit market. He insisted the FDA had “learned much from the harmful impact” that prescription opioids have had.

But Brown remains skeptical.

“Nothing is fundamentally being done to effect change in the regulation of opioids. If the FDA continues to encourage the pharmaceutical industry to turn out opioid after opioid after opioid, and the regulation of those opioids is no better than it was in 1995, then we’ll be cleaning this up for a long time,” said Brown.

Chris McGreal is the author of American Overdose: The Opioid Tragedy in Three Acts

Opioid Expert Accuses FDA of ‘Willful Blindness’ After It Approves Powerful New Painkiller

National Addiction News Article Here

An expert tasked with helping the Food and Drug Administration weigh potential new opioid drug approvals is openly calling out the agency for what he alleges are its continued missteps in handling the opioid crisis. In an interview with the Guardian Thursday, Raeford Brown claimed that the FDA has failed to learn from its past mistakes by approving the drug Dsuvia last year, the tablet form of an opioid painkiller up to ten times more potent than fentanyl.

Brown, a professor of anesthesiology and pediatrics at the University of Kentucky, was tapped to chair the FDA’s Anesthetic and Analgesic Drug Products Advisory Committee in 2018. One of the committee’s duties involved recommending whether or not Dsuvia should be approved. (The FDA rarely goes against the recommendations made by its outside committees.) Ultimately, the committee voted 10 to 3 for its approval. But Brown alleged to the Guardian that the approval process had been manipulated, and that the FDA has still largely avoided taking any serious action to curtail the role of legal opioids in the crisis.

“I think that the FDA has learned nothing. The modus operandi of the agency is that they talk a good game and then nothing happens. Working directly with the agency for the last five years, as I sit and listen to them in meetings, all I can think about is the clock ticking and how many people are dying every moment that they’re not doing anything,” he told the Guardian. “The lack of insight that continues to be exhibited by the agency is in many ways a willful blindness that borders on the criminal.”

In 2017, Dsuvia was actually rejected for approval by the FDA, with the agency calling for additional safety data from its maker, AcelRx. But the vote by the panel convened last October occurred while Brown was unable to attend—a decision Brown contends was intentional. Brown had long criticized the potential approval of Dsuvia, a stance he says the FDA was well aware of.

“There’s no question in my mind right that they did that on purpose,” he said. “The FDA has a lack of transparency. They use the advisory committees as cover.”

Brown isn’t the only one who had trouble with how the FDA ultimately approved Dsuvia. In a letter sent to the FDA last October, senators Joe Manchin (D-WV), Edward Markey (D-MA), Richard Blumenthal (D-Conn), and former senator Claire McCaskill (D-Miss) criticized the agency over Brown’s absence during the panel vote. The senators also criticized the FDA’s decision to not fully include another panel of experts, the Drug Safety and Risk Management Committee, in the approval process of Dsuvia.

Soon after its approval in November, FDA chief Scott Gottlieb went out of his way to tamp down criticism. In a statement, Gottlieb said that there were “very tight restrictions being placed on the distribution and use of this product.”

Dsuvia is a form of the opioid sufentanil, taken as a tablet that dissolves under the tongue. It’s currently approved for people with moderate to severe pain who haven’t responded to other treatments. The drug is supposed to be administered only in medically-supervised health care settings, such as hospitals and emergency rooms, by approved medical staff.

But sufentanil tablets like Dsuvia can still potentially be abused or improperly dosed to patients, according to the National Institute for Health and Care Excellence in the UK. And there’s still the possibility they can end up in the black market. The European Union approved a similar tablet version of sufentanil made by AcelRX, Dzuveo, last summer.

Brown, for his part, doesn’t buy Gottlieb’s assurances. And he thinks until the FDA has gotten its act together, no new opioid drugs should hit the market at all.

“They should stop considering any new opioid evaluation,” Brown told the Guardian. “For every day and every week and every month that the FDA don’t do the right thing, people drop dead on the streets. What they do has a direct impact on the mortality rate from opioids in this country.”

The FDA as well as AcerRX have not immediately responded to a request for comment from Gizmodo on Brown’s accusations.