Voluntary action—for now; validation of the REMS program
While news of the crisis in opioid abuse (of both legal and illegal versions) is unremittingly bad, one of newly appointed FDA Commissioner Scott Gottlieb’s first action is to call for a voluntary withdrawal of Opana ER (oxymorphone hydrochloride), marketed by Endo Pharmaceuticals. The product was originally approved in 2006, then was reformulated in 2012 as a tamper-resistant version. FDA did not approve a label revision to highlight the reformulation, however; and a recent “review of all available postmarketing data, which demonstrated a significant shift in the route of abuse of Opana ER from nasal to injection following the product’s reformulation,” has led to the action, according to an FDA statement. At March 2017 FDA advisory committee meeting, the panel of independent experts voted 18-8 that the benefits of reformulated Opana ER no longer outweigh its risks. Besides the abuse potential, drug injection by addicts has been shown to increase the transmission of a variety of diseases, including HIV and hepatitis C. Should Endo choose not to withdraw the product, FDA can then formally remove its marketing approval.
The action is the first ever withdrawal of an opioid from the market. “We are facing an opioid epidemic – a public health crisis, and we must take all necessary steps to reduce the scope of opioid misuse and abuse,” said FDA Commissioner Scott Gottlieb, MD. “We will continue to take regulatory steps when we see situations where an opioid product’s risks outweigh its benefits, not only for its intended patient population but also in regard to its potential for misuse and abuse.” On May 23, Gottlieb announced the formation of an opioid policy steering committee “to explore and develop additional tools or strategies FDA can use to confront this crisis.”
Endo issued a statement saying that it "is evaluating the full range of potential options as we determine the appropriate path forward." The company also noted that "this request does not indicate uncertainty with the product's safety or efficacy when taken as prescribed."
Since the reformulation in 2012, Opana, like most other opioids on the market, has been subject to a Risk Evaluation and Mitigation Strategies (REMS) requirement, which compels the manufacturer to perform education of the drug’s use and to perform postmarketing analysis (although the FDA announcement didn’t mention the REMS requirement, this is a likely source of the data the panel reviewed). The REMS program began with much fanfare in the late 2000s, but after a reassessment to require only expanded medication guides to be issued, has been fairly quiet in later years. Opioids have been under a so-called “class-wide” REMS mandate including both branded and generic forms. The current FDA REMS list has 70 entries; the class-wide REMS for opioids alone has 67.