An FDA advisory committee overwhelmingly panned the idea that Purdue Pharma's abuse-deterrent formulation (ADF) of oxycodone (OxyContin) "meaningfully reduced" overall opioid abuse, overdose and death.
Just two of the 28 members on the FDA's Drug Safety and Risk Management and Anesthetic and Analgesic Drug Products advisory committees voted "yes" on whether the reformulated OxyContin lessened overall abuse since it was introduced in 2010.
The panel voted 20-7 (one member abstained) that the drug did reduce abuse by non-oral routes; however, it was rejected in a vote of 1-26 (with one abstention) that the ADF version had a substantial impact on overdose rates.
"I do not think that the reformulation has shown a meaningful reduction in abuse overall by any specific group," said Lewis Nelson, MD, chief of medical toxicology at Rutgers New Jersey Medical School in Newark, who voted no on all three questions. Nelson said that the data were "exceptionally confounded, and dynamic in the nature of population."
"The problem with this product is that the perception, the marketing, the message is 'we've got a product that's going to help with the opioid crisis.' And it's really easy to overstate that," said Steven Meisel, PharmD, director of patient safety at Fairview Health Services in Minneapolis, who also voted no on all three issues.
Meisel said that there is a possibility that providers may prescribe more ADFs due to a false sense of security, emphasizing the need to "get rid of this term, 'abuse-deterrent formulation.'"
Sherif Zaafran, MD, of US Anesthesia Partners in Houston, the only advisory committee member to vote that OxyContin's ADF reduced non-oral abuse, overall abuse and overdose, said that the reduction in abuse by the intranasal and intravenous routes was sufficient evidence that the drug led to a "decreased chance of bad outcomes."
OxyContin's ADF -- which received FDA approval a decade ago -- - includes high-molecular-weight polyethylene oxide, a hard coating on the outside that makes tablets difficult to crush, dissolve or break. It also forms a gel when combined with water, aimed at preventing abuse by snorting or injection.
This advisory committee meeting was called simply to review Purdue's postmarketing data with ADF OxyContin, not because the company sought expanded drug labeling. Throughout two days of presentations, FDA staff emphasized that evidence was sparse that the newer version of the drug lowered overall abuse, despite some data that abuse by snorting or injection declined after the reformulation was approved.
Advisory committee members raised several concerns about the quality of data used in Purdue's postmarketing studies. The studies, which all compared abuse rates before the reformulation's approval to the post-approval period, were limited by several unmeasured confounders, including a dynamic population and changes to public health and government interventions that could have impacted the number of opioid overdoses and deaths.
Members were also critical of unintended consequences of the reformulated drug, such as a rise in abuse of illicit drugs like heroin or fentanyl and adverse events, which include reports of dysphagia and thrombotic microangiopathies.
Public comments echoed both sides of the ADF debate, with some pointing to the important role of reformulated opioids in mitigating the epidemic, while others stated that "abuse-deterrence" does not solve the major issue with the crisis: addiction.
"Purdue would like medical community regulators and the public to believe that the opioid crisis is a drug abuse problem," said Andrew Kolodny, MD, speaking on behalf of the organization Physicians for Responsible Prescribing.
"But we don't have an epidemic of drug abuse," Kolodny continued. "We have an epidemic of opioid use disorder."
In an evaluation of four postmarketing studies conducted by the drug's manufacturer, FDA staff determined that only one of the studies provided good evidence that ADF OxyContin significantly reduced opioid abuse by non-oral routes. Findings from the retrospective study, which was conducted in a population being assessed for substance abuse treatment, indicated that OxyContin abuse by injection and insufflation dropped 52% after the OxyContin reformulation.
But there was also no decline in the most common form of abuse -- swallowing opioid tablets.
Other studies conducted by Purdue, which analyzed data from treatment centers, poison control centers, and both commercial and Medicaid insurance claims, did not produce solid evidence that the reformulation lessened overall OxyContin abuse.
The meeting was originally scheduled to take place in July 2015, when Purdue requested new labeling for the ADF product to include claims of reductions in overdose and death. But the company withdrew that application just before FDA staff reviews were due to be posted.
The FDA is not required to follow recommendations of its advisory committees, but it typically does. The agency will use the recommendations to determine regulatory actions for OxyContin's ADF.