Megan Polanin, National Center for Health Research: June 26, 2018
Thank you for the opportunity to speak today on behalf of the National Center for Health Research. I am Dr. Megan Polanin. Our research center analyzes scientific and medical data and provides objective health information to patients, providers, and policymakers. We do not accept funding from industry, so I have no conflicts of interest.
We strongly support the FDA’s efforts to encourage the development of opioid analgesics that deter abuse. As with any other drug the FDA evaluates, these opioids should be held to a high standard for approval to maximize the probability that the risk of abuse is actually lower than it would be without properties designed to deter abuse.
We all know that oxycodone is one of the most highly abused opioids. For example, from 2012-2106, calls to poison control centers indicated that intentional abuse of oxycodone was only surpassed by heroin. RADARS and NAVIPPRO databases both found that oxycodone was the second most highly-abused opioid. In addition, oxycodone was the second most commonly reported abused drug among patients entering treatment for Opioid Use Disorder.
With this context in mind, please consider these two questions as you evaluate Remoxy’s patient and public health benefit/risk ratio:
Has the sponsor shown that Remoxy has properties that will deter abuse by oral, nasal, and intravenous routes of administration? If Remoxy can prevent abuse through all three known routes of abuse, that would be a very positive step for preventing further misuse and abuse and initiate a higher standard for abuse-deterrent drugs. That is not the case with this drug.
- The sponsor’s Category 1 studies showed that Remoxy’s physical properties successfully deterred abuse via injection, snorting, and smoking.
- The human potential abuse study indicated that Remoxy might deter intranasal abuse. For example, when compared with oxycodone IR, Remoxy was more difficult to use intranasally and less likeable for abusers.
However, we are concerned that results from the oral human abuse potential study showed that chewed Remoxy did not deter abuse compared with crushed oxycodone IR tablets for half of the primary endpoints. And, as the FDA stated, the significant findings may not be clinically relevant. In addition, the FDA’s Category 1 studies showed that oxycodone can, in fact, be extracted from Remoxy. Finally, excipient risk has not yet been adequately tested.
It is well known that abusers of the drug can be very creative in finding unique techniques to overcome those deterrents. Because oxycodone is a highly abused drug, we are concerned that this drug could still be abused orally and intravenously. Finally, we want to point out that Remoxy was compared with Roxicodone, an oxycodone IR drug, and not compared with current abuse-deterrent oxycodone ER/LA products on the market.
What are the potential unintended harms of Remoxy in the real world? We know that patients continue to abuse ER/LA oxycodone with abuse-deterrent formulations and that oxycodone ER tablets are particularly vulnerable for abuse. In the laboratory setting, Remoxy appears to meet the FDA’s current standards for deterring intranasal abuse. Whether its abuse-deterrent properties are effective in the real world is a much more difficult question that will require postmarketing data. We know from previous experience that so-called abuse-deterrent opioids are sometimes abused more widely than current laboratory studies suggest: Opana ER is one example.
To reduce the opioid epidemic, the FDA must hold pharmaceutical companies to a high and truthful standard. Remoxy did not meet the FDA’s standards for oral abuse, and it remains unclear whether it can be abused intravenously. The safety of the excipient is also in question. Please carefully consider the risks of putting another drug with abuse-deterrent labeling on the market that could result in misuse and abuse in the real world. We urge this Advisory Committee to vote that the benefits of this drug do not outweigh its risks.
[The FDA should require that any drug labeled as “abuse-deterrent” have have a black box warning indicating that, although the drug may have properties that make it more difficult to abuse, it is still highly addictive.]
Thank you for the opportunity to share our perspective.
The Anesthetic and Analgesic Drug Products Advisory Committee (AADPAC) and the Drug Safety and Risk Management Advisory Committee (DSaRM) voted 14-3 against approval of Remoxy. Read more about the meeting here.