Grisly and dramatic testimony jarred the public-comment segment of the FDA advisory panel on Zohydro for chronic pain, as parents of opioid casualties begged committee members to turn thumbs down on Zogenix Inc.'s extended-release hydrocodone.
It may have done the trick.
The Anesthetic and Analgesic Drug Products Advisory Committee voted against recommending approval of Zohydro, touted as potentially the first hydrocodone capsule to offer less frequent dosing without the risk of liver injury since, unlike Abbott's popular Vicodin, Zohydro contains no acetaminophen.
Specifically, in its third, ultimate vote on the compound, panelists balloted 11 no and 2 yes, with 1 abstention. The vote will be discussed for a while, since Zogenix seems to have satisfied requirements that previous opioids in the class have met to win FDA approval, but the agency's advisors voiced increasing worry about abuse in the class itself.
From the outset, regulators faced a quandary in Zohydro (hydrocodone bitartrate), which apparently works as well and maybe as safely as other, approved opioids. It may be even safer, since Zohydro, unlike popular Vicodin, a combination of acetaminophen and hydrocodone – contains none of the former.
Troubling, though, is the potential for abuse. Daniel Busch, psychiatrist at Northwestern University's Feinberg School of Medicine, said, "immediate-release hydrocodone can be extracted simply by crushing the [drug] particles." Bush testified that his son died as a result of opioid addiction.
The dilemma for the FDA is that if Zohydro is determined to have the same safety issues as others in the class, then whatever action is taken on Zogenix's candidate should apply to all, including those approved and marketed.
Robert Rappaport, director of the FDA's Division of Anesthesia, Analgesia, and Addiction, asked that, if panel members decide that special measures of any kind be taken with regard to Zohydro, they provide "clear examples of how this product is different from other products in this class [of potent, single-entity opioids]" and "consider the implications" of what they do.
He urged the committee to consider "the regulatory framework within which those of us in FDA must function. The word was must function."
One man testified about the shotgun suicide of his grown son, who had been prescribed hydrocodone. A woman said her son hanged himself, after taking the medicine and hallucinating. Another victim took one pill from someone else's prescription, quit breathing and died.
Jeffrey Reynolds, director of the Long Island Council on Alcoholism and Drug Dependence, praised the FDA's program for risk evaluation and mitigation strategy. "Still, that's not enough," he said, insisting that the drugs themselves need to be formulated as tamper-proof. Otherwise, he said, society will forever be playing a "game of Whac-a-Mole as we struggle with the drug du jour," and Zohydro could "become the drug of choice for addicts in 2013."
The panel's first vote – the balloting on Zohydro's efficacy – could have inspired bad jokes about pain medications. At first, the count was 7 yes and 6 no, with one abstention. But as the voters were polled individually, one said she had hit the wrong button, so the count should be 8 yes, 5 no. This was noted for the record, and the official count was unchanged. Next, the abstainer was undecided at the last minute, but "probably should have pressed 'no.'"
Panelist Jeanmarie Perrone, of the department of emergency medicine at the University of Pennsylvania in Philadelphia, voted no and cited "a very modest change in pain scores" with Zohydro that were only made persuasive by way of "a lot of methodologic reworking."
The second vote, on safety, was more definitive: 9 no, 5 yes. Alan Kaye, of the Louisiana State University School of Medicine in New Orleans, was among the nay-sayers. "I happen to live in the real world, and I would think that the study population is very different than the real-world population," he said.
Rodney Mullins, national director of Community Health Advocates in Atlanta, served as the panel's acting consumer representative. He also turned thumbs down on Zohydro.
"The sponsor did not assure me, from a public-health perspective, and that's the area I want to deal in," Mullins said. "They didn't offer any suggestion on how they would limit use to only to the prescribed patient."
He also complained that no neurological studies were performed.
James Ware, director of biostatistics at the Harvard School of Public Health in Boston, had other reasons for his negative vote. "I'm unhappy about the question," he said, noting that, by asking if Zohydro was safe, the FDA meant to ask whether the drug's safety profile was acceptable – which are not the same questions in this instance.
San Diego-based Zogenix halted trading of its stock (NASDAQ:ZGNX) while the hearing was under way.