Wednesday morning, December 5, the U.S. Food and Drug Administration posted briefing documents for Friday’s Anesthetic and Analgesic Drug Products Advisory Committee (AADPAC AdCom) review of Zohydro, the first single‐entity, extended‐release hydrocodone pain medicine to be reviewed by the FDA. Zogenix is seeking an approval of Zohydro for the treatment of chronic pain in opioid‐experienced patients.
After an initial read of the documents, we note that within the FDA materials, the agency cites the belief that similar to what occurred with oxycodone products, a product like Zohydro will likely be abused more than combination products. However, we believe this is a known concern and likely the reason for Friday’s panel. The abuse of Zohydro is also expected by the FDA to be less than with oxycodone products based on emergency room data from the Drug Abuse Warning Network (DAWN). The FDA cites an abuse ratio of 14 emergency department (ED) visits per million tablets dispensed for hydrocodone combination products, versus the 24 ED visits per million tablets dispensed for oxycodone combination products and 85 ED visits per million tablets dispensed for oxycodone single‐entity, extended‐release products.
Within the FDA documents, there is no mention of liver toxicity of the combination hydrocodone/acetaminophen products, while the Zogenix briefing material highlights this as a reason for a product such as Zohydro. Combination hydrocodone/acetaminophen
products are the leading cause of acute liver failure in the United States, and a single‐entity hydrocodone such as Zohydro has been cited by past AdComs on the topic as a reason not to pull the combination products from the market. The question posed by the FDA to the AdCom regarding the abuse potential of Zohydro will be for discussion, not a vote, which suggests that abuse potential will be weighed within the final question of approval.
The FDA also is seeking guidance on additional postmarketing risk‐mitigation requirements in question 4 for discussion. We believe this is a positive since Zogenix management has offered within the briefing documents its own program, the Zohydro ER Safe Use Initiative, to supplement the FDA‐required REMS program for all extended‐release and long‐acting opioids (ER/LA). This extends our belief that Zogenix will look to be a responsible marketer in this space, which may be viewed positively by the panel, as we believe existing players such as Purdue
Pharmaceuticals, have a rather strained relationship with the FDA. The draft questions that will be posed to the committee are included on the following page.