Posimir is a non-opioid being developed for post-surgical pain. It is designed to be injected into the surgical site, where it delivers bupivacaine for up to three days post-surgery.
Yesterday the U.S. Food and Drug Administration (FDA) Anesthetic and Analgesic Drug Products Advisory Committee (AADPAC) met to discuss DURECT Corporation’s Posimir. The adcom had a 6-to-6 vote on whether to recommend approval of the drug.
Posimir is a non-opioid being developed for post-surgical pain. It is designed to be injected into the surgical site, where it delivers bupivacaine for up to three days post-surgery.
Although the FDA isn’t obligated to follow the committee’s recommendation, it usually does. That becomes much less clear when there’s an even split on the recommendation.
“We appreciated this opportunity to present an in-depth overview of our Posimir data and discuss it with the committee,” said James E. Brown, president and chief executive officer of Durect. “We are encouraged by the support from a number of the Committee members. We continue to believe the data meets all of the regulatory requirements and that the weight of the evidence supports approval. We look forward to working with the agency as it completes its review of the Posimir application.”
Some of the panel members expressed concerns over nausea, vomiting and bruising at the surgical site that some patients receiving Posimir experienced.
“It is slightly better than placebo, but very slightly better, (that) coupled with some potentially minor safety concerns make the benefit to risk calculation challenging,” said Abigail Shoben, associate professor of Biostatistics at The Ohio State University and a member of the adcom.
There were also concerns about how the drug is administered directly into the surgical incision. Panel members requested additional studies on the effects of the drug when given intravenously.
“The data was consistent and there are some unknowns that don’t make sense with the rationale I heard,” said another adcom member, Joseph O’Brien, chief executive officer of the National Scoliosis Foundation in Massachusetts.
However, O’Brien voted for approval. “Despite all these concerns, at the end of the day, we do have a need for opioid-sparing medication,” he said.
The drug was originally rejected by the FDA over safety concerns in 2014. After that, the company ran a two-part trial that had a placebo arm and a bupivacaine comparator arm, which was added at the request of the FDA, although the company discontinued the placebo arm.
There were safety problems, especially neurological adverse events, such as somnolence, dizziness, and dysgeusia—distortion of taste.
In a research note to clients earlier this month, analysts with Stifel estimated the drug had only a 30% likelihood of approval because of its regulatory history.
All in all, the company isn’t starting off the year very well. On Jan. 2, it announced results from its Phase IIa trial of DUR-928 in mild to moderate plaque psoriasis. The drug did not show a benefit over placebo based on Investigator’s Global Assessment (IGA), the scoring system for the primary analysis, or in any of the secondary analyses.
Brown said at the time that the company did not plan to continue developing the topical therapeutic. “With the recently announced positive results from our Phase IIa alcoholic hepatitis trial, our focus moving forward with DUR-928, will be on completing the NASH trial in the first half of this year and initiating the Phase IIb AH trial in the middle of the year.”
