Pfizer's Troxyca Gets Mixed Review From FDA Advisors
Oxycodone/naltrexone combo meets current safety standards, but is that enough?
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by Kristina Fiore
Associate Editor, MedPage Today
A joint FDA advisory committee gave a tepid endorsement (9-6) to extended-release oxycodone/naltrexone (Troxyca) for treating severe pain, but such close votes are often considered "null" among FDA observers.
In separate votes, the committee voted in favor of abuse-deterrent labeling for the intranasal (11-to-4) and intravenous (9-to-6) routes of abuse, but against language that it prevents oral abuse (6-to-9) for the drug, formerly known as ALO-02.
Many panelists who said "yes" to approving the drug said they did so based on a "narrow" reading of the indication, and the current standard of approval for extended-release and long-acting opioids.
"It was demonstrated to be as safe and as effective as our current standard, but evidence points to this class of drugs not being safe or effective for chronic pain in general, so I wasn't comfortable voting "yes" for this product," said Melinda Campopiano, MD, of the Substance Abuse and Mental Health Services Administration (SAMHSA), who voted against approval.
"I agree that it meets the current standard, that it is no less safe or less effective. But that current standard is what brought us the opioid epidemic we are dealing with," said Tobias Gerhard, PhD, of Rutgers University in New Brunswick, N.J., who also voted against approval. "We have to start making changes at some point."
The two committees -- the Anesthetic and Analgesic Drug Products Advisory Committee (AADPAC) and the Drug Safety Risk Management Advisory Committee (DSaRM) -- met 2 days in a row to consider two new extended-release opioids that were hoping to win abuse-deterrent labeling.
On Tuesday, they gave a hesitant vote in favor of Teva's hydrocodone drug Vantrela. But during both meetings, panelists generally agreed that the criteria for awarding abuse-deterrent labeling have to be better defined, and that putting additional extended-release opioids on the market may not be the best thing for public health at this time.
"We've heard over the last 2 days -- and it's beginning to be repetitive -- a drumbeat for limiting the number of long-acting/extended-release drugs on the market," said Raeford Brown, MD, of the University of Kentucky in Lexington. "We worry constantly about our ability to make the right decision -- which we all want to do -- without being able to see the post-marketing data."
"Again I'm going to ask the agency to make some concerted effort to get those data out so we can begin to know if the decisions we're making are the right decisions," Brown said.
Panelists noted that this meeting was unique in that Pfizer has a similar product, Embeda, on the market that uses the same technology. It involves a capsule of tiny beads that package the opioid around a core of naltrexone, a potent opioid antagonist, in hopes of reducing abuse.
Embeda combines morphine and naltrexone, while Troxyca would combine oxycodone and naltrexone. The idea is that patients who have trouble swallowing could open these capsules of beads and spread them on food -- something that couldn't be done with many other forms of abuse-deterrent opioids.
Embeda didn't receive abuse-deterrent labeling when it was approved in 2008, but the FDA did award such labeling in 2014.
Sharon Hertz, MD, director of the FDA's division of anesthesia, analgesia, and addiction products, said the labeling wasn't awarded in 2008 because the agency didn't have any guidance on abuse-deterrent labeling at that time.
"We did not know at the time what to do with them," Hertz said. "As a result we opted not to label -- not because we decided it was good or bad."
Post-marketing studies on Embeda are due in 2019, but no interim data were available -- a major complaint of the panelists, who continued to point out that there is no evidence that any opioid with abuse-deterrent labeling actually reduces abuse.
"This technology is already on the market," Campopiano said. "We have the opportunity to make a better informed decision if we wait for that postmarketing data."
Panelists were also concerned that the drug, while resistant to abuse via crushing and several types of dissolution, appeared to be easily dissolved in three commonly available solvents that are safe for consumption and easy to obtain, although it might take some time to do so.
"Once the recipe is out there, it doesn't matter if they had 5,000 data points that didn't work," said panelist Jeanmarie Perrone, MD, of the University of Pennsylvania in Philadelphia. "Once you get the one that does work, it will be the one that proliferates, and it's pretty simple based on what we've looked at."
Michael Sprintz, DO, of the Sprintz Center for Pain and Dependence in The Woodlands, Texas, said that while the extra time might deter some potential abusers, it won't deter operations looking to produce the drug at scale.
"We have to think about the real world, which is not just abuse, but also diversion, which creates a market for addiction," Sprintz said. "We have people who may be doctor shoppers or drug diverters with the intent to sell."
Perrone also mentioned that the highest dose of the drug -- 80 mg twice daily -- would be in excess of limitations recommended by recent CDC guidelines on opioid prescribing.
Six ER/LA opioids have abuse-deterrent labeling: OxyContin (oxycodone), Targiniq (oxycodone/naloxone), Embeda (morphine sulfate/naltrexone), Hysingla (hydrocodone), Morphabond (morphine sulfate), and Xtampza (oxycodone).
It's not clear when post-marketing data from these abuse-deterrent formulations with regard to how they impact abuse, addiction, overdose, and death will be available.
Gerhard noted that abuse-deterrent labeling could give patients and physicians the wrong impression: "If prescribers think it's safer and that patients are less likely to get addicted, none of this has been shown with any data. We have to be very careful granting that status."
LAST UPDATED 06.09.2016
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