The Food and Drug Administration (FDA)’s Anesthetic and Analgesic Drug Products Advisory Committee and Drug Safety and Risk Management Advisory Committee voted against (2 “yes”, 24 “no”) the approval of Aximris XR (oxycodone extended-release tablets; Intellipharmaceutics) for the management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate.
According to Intellipharmaceutics, Aximris XR was developed with abuse-deterrent properties that make the tablet more difficult to manipulate. Specifically, when ground and exposed to an aqueous environment, the powder quickly becomes viscous, thereby making it difficult for the material to pass through a hypodermic needle. The tablet is also resistant to dose dumping in the presence of alcohol and to heat manipulation for the purpose of vaporization and smoking.
This is the second review cycle for the New Drug Application (NDA) for Aximris XR, which was submitted via the 505(b)(2) regulatory pathway. The application includes data from clinical pharmacology studies as well as pharmacokinetic studies that provided evidence that the investigational opioid was expected to be bioequivalent to Oxycontin (oxycodone extended-release tablets; Purdue Pharma).
In the updated submission, Intellipharmaceutics included data from 2 additional studies that investigated the abuse potential of Aximris XR via intranasal and oral routes of administration, an issue raised by the FDA in a Complete Response Letter in 2017. Study results showed that while the investigational opioid contained improved properties that would likely deter IV abuse, the data did not support abuse deterrence for the oral and intranasal routes. Moreover, pharmacokinetic results demonstrated higher systemic exposure with Aximris XR following intranasal administration.
Given these results, the panel questioned whether an agent could really be called “abuse-deterrent” if it only deterred abuse through a single route of administration. According to meeting documents, “The evaluation of an abuse-deterrent formulation should take into consideration the known routes of abuse for the non-abuse-deterrent predecessor or similar products, as well as anticipate the effect that deterring abuse by 1 route may have on shifting abuse to other, possibly riskier routes.”
Although not bound by the committees’ recommendations, the FDA does take them into consideration when making decisions on approval.
For more information visit fda.gov.
This article originally appeared on MPR