Purdue's withdrawal of a supplemental New Drug Application related to its abuse-deterrent formulation of OxyContin has raised questions about postmarketing requirements for the drug.
Citing a need for additional analyses of data on the product, the company one day before agency staff would have released their evaluation of the application, prior to an advisory committee meeting scheduled for next week.
The says the meeting was to review "postmarketing studies evaluating the misuse and/or abuse of reformulated OxyContin" and whether those studies "have demonstrated that the reformulated product has a meaningful impact on abuse."
Indeed, the agency's stated specifically that, as a condition of approval, Purdue had to "conduct epidemiological studies to address whether the changes made to the OxyContin (Oxycodone Hydrochloride Controlled-Release) Tablets formulation that are the subject of this application result in a decrease in misuse and abuse, and their consequences: addiction, overdose, and death."
But the agency now says these studies were never required, giving Purdue the option of presenting its data on the actual abuse-deterrence of its reformulated product -- for which it had already earned abuse-deterrent labeling in 2013.
Eric Pahon, a spokesperson for the FDA, said the 2010 letter was issued under a different administration, led by Bob Rappaport, MD, who retired from the agency last September. Current FDA officials could not explain why the initial letter included the epidemiological postmarketing requirements.
"This is a voluntary study that Purdue was doing," Pahon said. "FDA wanted them to do so, but it was not required. We have no authority to enforce them to do so." Rappaport could not be reached for comment.
In a statement, Purdue's head of regulatory affairs Richard Fanelli said the company has decided to do additional analyses of its data on abuse rates.
Purdue reformulated OxyContin in 2010 in an effort to curb a scourge of abuse that was tied to the drug. At that time, the FDA expressed concerns that the postmarketing studies Purdue had proposed to track these outcomes wouldn't "successfully capture the necessary information that will allow us to assess the impact, if any, attributable to the change [in formulation]."
Although the FDA now says there are no required epidemiological postmarketing studies specifically for reformulated OxyContin, its postmarketing trials database .
The first required postmarketing study calls on the company to "provide quantitative estimates of the serious risks of misuse, abuse, addiction, overdose, and death" for the general class of extended-release and long-acting opioids. Those results are not due until June 2018, and there was no requirement for results pertaining specifically to abuse-deterrent products.
The four other trials are supposed to also develop and validate measures of those parameters, evaluate the risk of hyperalgesia, and to validate other measures of abuse including doctor-shopping.
Several studies have been published regarding reformulated OxyContin's impact on abuse rates. Early studies showed that the new formulation did reduce abuse in the short term. But findings published in JAMA Psychiatry last March showed those reductions eventually leveled off.
It remains to be seen whether Purdue will resubmit those data and prompt another advisory committee meeting.