FDA advisors voted 19-0, with one abstention, that the immediate-release oxycodone formulation RoxyBond should be approved to treat chronic pain, and the majority agreed that it could carry abuse-deterrent labeling for both the intranasal and intravenous routes of abuse.
In a joint meeting of the Anesthetic and Analgesic Drug Products Advisory Committee (AADPAC) and the Drug Safety and Risk Management Committee (DSaRM), panelists voted that there was enough evidence of abuse-deterrence to award label claims for both the intranasal (19-1) and the intravenous (16-4) routes of abuse.
If approved, RoxyBond would be the first immediate-release opioid product that can be marketed as abuse-deterrent. Currently, there are nine opioids approved with abuse-deterrent labeling, but they are all extended-release products.
"I think this medication represents an important advance as the first immediate-release formulation with the possibility to deter abuse," said panelist Brian Bateman, MD, of Harvard. "While it's not perfect, it does provide some barrier to abuse via the intranasal and intravenous routes."
But Ronald Litman, DO, of the University of Pennsylvania, who abstained from the approval vote, said that while he believes RoxyBond will "work just fine as an opioid to treat pain," he couldn't vote yes on a philosophical basis.
"I think there is so much money at stake here," he said. "So many state legislatures have passed or are considering laws that physicians have to prescribe the abuse-deterrent formulation when available. It's no surprise that so many companies are jumping on this bandwagon ... All of the organizations that spoke here [during the open public hearing], they're all supported by drug companies. Even the one who said he didn't get any money displays an Inspirion logo on his website."
"Abuse-deterrent formulations are a red herring, a distraction from the real problems underlying the opioid crisis," he added.
Panelist Arthur Kibbee, RPh, PhD, of Wilkes University in Pennsylvania, who voted in favor of approval, said he agreed with Litman that a push toward abuse-deterrent formulations "isn't the answer to the opioid abuse problem. It's going to take a large change in the way we handle those addicted to abusable drugs. This is perhaps a temporary, but not final, answer."
RoxyBond was developed by Inspirion Delivery Sciences, which is seeking approval via the 505(b)(2) pathway using Roxicodone as the reference listed drug. Like Roxicodone, RoxyBond would be available in 5, 15, and 30 mg doses -- but unlike Roxicodone, it would be hard to crush and would turn viscous in dissolution attempts, with the help of the company's SentryBond abuse-deterrent technology, the drugmaker said.
Some of the concerns voiced by panelists were similar to those that have repeatedly come up at opioid-related advisory committee hearings, including the fact that the formulation could potentially deter abuse but wouldn't completely eliminate it. Also, the drug would not deter abuse via the oral route, and there are still insufficient post-marketing data to assess whether abuse-deterrent formulations actually reduce abuse in the real world.
When voting on intranasal abuse label claims, many panelists said they were convinced by the company's data on drug likability, which showed the older formulation of Roxicodone to be more preferable.
The vote on intravenous route label claims was more controversial. Many panelists said they were convinced by the syringability data, but others noted significant caveats.
Mary Ellen McCann, MD, MPH, of Children's Hospital Boston, who voted no on IV abuse labeling, said although it required greater volume extraction, it "wouldn't be difficult to make two-thirds of the drug available, and the easy way to do that is to use two tablets. If you really wanted to abuse it, it would be easy to do in an IV fashion."
Terri Warholak, PhD, RPh, of the University of Arizona, who also voted against IV abuse labeling, noted that she was "able to find product-specific information online about how to [abuse] the drug right now and it's not even on the market yet."
Panelists also warned that the excipients used could cause other problems if abused via the intravenous route -- especially as many of them were recently involved in an FDA advisory committee meeting on the adverse effects of intravenous use of Opana.
"There are not a lot of data regarding IV administration of methyl methacrylate," said Kevin Zacharoff, MD, of SUNY Stony Brook in New York. "I'm concerned about the negative outcomes related to that. I'd want that to be in the label."
David Craig, PharmD, of Moffitt Cancer Center in Tampa, Fla., said he considers such potential for adverse events a "real concern for products like this, especially when they're not intended to be used that way. It's hard to control for those problems, but I would support a black box warning for the potential harm from injecting."
Elaine Morrato, DrPH, MPH, of the University of Colorado, agreed that this is a "unique problem that arises from misuse. I know that's a difficult space to regulate, but because of prior evidence with other drugs, there is a precedent to be concerned."
Morato noted that the FDA would have to decide whether such additional study of excipients would be a premarket or postmarket requirement.