An FDA advisory committee has voted unanimously against approval of an oral combination of morphine and oxycodone (Moxduo) for acute pain.
In the 14-0 vote, panelists concluded there wasn't sufficient evidence to support that the combined drug is safer than either morphine or oxycodone alone for moderate to severe acute pain. The FDA is not obliged to go along with its advisory committees' recommendations but it usually does.
"It is the sense of this committee that the applicant has not provided sufficient evidence to support a claim that Moxduo is safer than morphine or oxycodone," committee chairperson Randall Flick, MD, MPH, of the Mayo Clinic in Rochester, Minn., said when summarizing the committee's discussion. "The primary failing was in study design and the inability of the committee to be able to rely with confidence on multiple post-hoc analyses."
The committee was focused on post-hoc analyses regarding oxygen saturation data from Study 022. Drug sponsor QRxPharma had received two complete response letters (CRL) from the FDA prior to today's committee meeting.
After initial NDA submission in August 2011, the agency had requested in a June 2012 CRL that the drug show some type of benefit over its components, and that the answer may lie in analyses from Study 022, in which 375 patients who'd had bunionectomy received either Moxduo, morphine, or oxycodone.
FDA said the company could perform post-hoc analyses of this data -- with a focus on oxygen saturation levels -- since the trial wasn't initially designed as pivotal phase III study.
The company said it had addressed the FDA's concerns and that a second advisory committee meeting had been set for July 2013, but had to be postponed because of a timing error in the pulse oximetry data that couldn't be fixed before the meeting.
FDA then issued a second CRL based on the data that were in hand in August 2013. In the meantime, QRxPharma was developing a plan to validate the data to be used in the analyses, which was completed by November 2013.
The FDA said these re-analyzed data would be acceptable to present before the advisory committee, but panelists were ultimately not convinced by the results. It also unanimously voted (14-0) that there was insufficient evidence to determine whether Moxduo provided additional safety beyond each of its individual components.
"I wish there was an opiate that could be counted on to decrease respiratory depression and maybe one day there will be," said panelist Gregory Terman, MD, PhD, of the University of Washington in Seattle. "But at the moment, opiates given by schedule have no usefulness in the postoperative period, and that is why [extended-release long-acting opioids] are not appropriate for post-operative pain."
Some panelists said the data were hypothesis-generating, and responded to FDA requests for suggestions for the design of future trials, which included looking at which subpopulations may benefit.
One panelist also suggested considering drug likability studies to better understand potential abuse risks with Moxduo.
"Future, more appropriately designed studies would be helpful," Flick said. "The committee does not suggest that Moxduo is either beneficial or not beneficial; the [committee] simply feels that the evidence is insufficient to make a determination either way."