Panel Recommends Against Approval of Hydrocodone Capsules

Emma Hitt, PhD


December 10, 2012

The US Food and Drug Administration's (FDA's) Anesthetic and Analgesic Drug Advisory Committee of independent experts voted 11 to 2, with 1 abstention, to recommended against approval of hydrocodone bitartrate extended-release capsules (Zohydro ER, Zogenix), a formulation of hydrocodone without acetaminophen for the treatment of moderate to severe chronic pain.

Most panel members voted that the drug had met regulatory requirements for safety and efficacy as indicated by their responses to questions on efficacy and safety. However, the last question to be voted on — "Based on the data presented and discussed today, do the efficacy, safety and risk-benefit profile of Zohydro ER support the approval of this application?" — garnered mostly negative responses.

The main concern of those voting "no" was that the potential for abuse of these agents. Because the product does not include acetaminophen, the potential for abuse may be even greater.

"My negative vote was not about this drug per se," said panel member James H. Ware, PhD, from the Harvard School of Public Health, Boston, Massachusetts, "but there's a problem with this class of drugs, and some drugs have been approved with similar data. I think the sponsor has met the expectations of the FDA with the evidence they have provided," he said.

Jane Maxwell, PhD, from the University of Texas at Austin, also voted "'no." "I very much want to see a reformulated tamper-resistant product," she said. "I would also like to see a much stronger (Risk Evaluation and Mitigation Strategy [REMS]), with better quality control of the training…and much better oversight regarding the data surveillance."

The final decision to approve the drug will be made by the FDA by March 1, 2013, and the FDA usually follows the opinion of its expert panels.

Hydrocodone bitartrate extended-release capsules were evaluated in more than 1100 patients with chronic pain in a phase 3 efficacy study and an open-label phase 3 safety study. Both studies met their primary efficacy endpoints.

Side effects considered related to treatment included constipation, nausea, somnolence, and headache, which were observed as expected with opioids.

"Zogenix recognizes and appreciates that prescription opioid misuse and abuse is a critical issue," noted Stephen Farr, PhD, president and chief operating officer of Zogenix, in a statement issued after the vote. "However, it is also important to remember that there is a documented patient need for an extended-release hydrocodone medicine without acetaminophen. We remain confident in the measures we have proposed to support safe use of Zohydro ER and are committed to continuing to work with the FDA through the review process to bring this treatment option to this specific patient population."

According to the manufacturer's release, if approved, the product will be classified as a Drug Enforcement Agency Schedule II drug, subject to stricter prescribing and dispensing rules compared with the currently prescribed hydrocodone products. In addition, the REMS will be consistent with the recently introduced FDA-approved REMS for extended-release and long acting opioids.