Hung jury vote leaves FDA with a difficult decision on Durect's non-opioid painkiller
A split advisory panel vote on Durect’s non-opioid drug to manage post-surgical pain is only going to make the FDA’s task harder.
After FDA staff reviewers issued an internal review that underscored their unease with the side-effect profile of the long-acting anesthetic posimir — on Thursday a panel of independent experts could not reach a consensus on whether to back the therapy.
Six panelists endorsed approval, while the remaining six dissented. The therapy is a formulation of the anesthetic bupivacaine and is designed to manage pain up to three days following surgery after being administered directly into the surgical incision.
Posimir has a checkered past. Durect, which originally partnered with Novartis on the program, first submitted an application to market on the basis of two pivotal studies. The FDA spurned the application in 2014 over safety concerns. Durect then conducted the PERSIST study, hoping to quell the agency’s concerns — but that trial failed its main efficacy goal. Nonetheless, Durect resubmitted a marketing application.
The US drug regulator has intensified its efforts to stem the tide of opioid abuse, overdose, and addiction, fiercely scrutinizing the pharmaceutical architects of the prescription painkiller crisis. So despite persistent safety concerns associated with posimir, the prospect of ‘opioid-sparing’ was appealing to some panelists.
“The data was inconsistent and there are some unknowns that don’t make sense with the rationale I heard,” said Joseph O’Brien, chief of Massachusetts-based National Scoliosis Foundation, who endorsed posimir.”Despite all these concerns, at the end of the day, we do have a need for opioid-sparing medication,” he said, as cited by Reuters.
Panelists against approval expressed their unease with posimir’s efficacy, with some suggesting the therapy’s duration of action was limited to 12 to 24 hours, echoing the FDA staff review issued on Tuesday. Concerns about safety lingered with panelists on either side of the vote, and some suggested additional studies were warranted to demonstrate rescue in the event of accidental intravenous administration.
A 50/50 split vote is rare. Last year, a pill for patients with the less common type 1 diabetes, who produce no insulin, was the subject of an atypical hung jury vote at an FDA panel. Experts were divided evenly over whether the life-threatening risk of diabetic ketoacidosis associated with the drug, sotagliflozin, offset its benefit — the FDA eventually rejected the diabetes therapy.
Some panelists deliberating on posimir seemed more open to considering the therapy’s data as evidence of opioid-sparing compared to a November 2018 AdCom on opioid-sparing endpoints, Cowen’s Boris Peaker wrote in a note, which drew comparisons between posimir and two other bupivacaine painkillers: HTX-011 from Heron $HRTX and Exparel from Pacira $PCRX.
“Despite the questionable data, the ‘yes’ votes were primarily driven by the time to opioid rescue data,” Peaker wrote. “If time to opioid rescue does become a significant endpoint, HRTX’s data appears to be stronger than PCRX in cross-trial comparison. As such, we see this as another opportunity for HTX-011 differentiation vs. Exparel.”
Pacira’s J&J-partnered, long-acting post-op bupivacaine painkiller Exparel generated net sales of about $331 million in 2018. Heron’s HTX-011 — a formulation of bupivacaine and the non-steroidal anti-inflammatory drug (NSAID) meloxicam — received an unexpected rejection due to manufacturing concerns last year, but is on track to secure approval by March.
Earlier in the week, after an FDA advisory committee voted unanimously against Nektar Therapeutics opioid painkiller — a formulation not engineered to facilitate abuse deterrence from physical manipulation — the company abandoned the drug.