The Food and Drug Administration (FDA)’s Anesthetic and Analgesic Drug Products Advisory Committee (AADPAC) was split (6 to 6) on its decision as to whether Posimir (bupivacaine extended-release solution; Durect) should be approved for postsurgical analgesia.
The investigational treatment is a new formulation of bupivacaine designed to be administered directly into the surgical site. The depot product uses a sucrose-based biodegradable matrix (sucrose acetate isobutyrate) that allows for bupivacaine to be released into the adjacent tissues over the course of 72 hours.
The clinical program for Posimir included 7 trials involving patients undergoing arthroscopic shoulder surgery, open inguinal hernia repair, hysterectomy, colectomy, laparotomy, or laparoscopic cholecystectomy. However, the efficacy data were found to be inconsistent across these trials; only 2 studies (1 arthroscopic shoulder repair study and 1 hernia repair study) showed a statistically significant treatment effect in favor of Posimir and the majority of effect was noted in the first 24 hours after surgery.
To address safety concerns raised by the FDA in a 2014 Complete Response Letter, the Company analyzed data from previously completed studies and conducted an additional trial (PERSIST). The PERSIST study was a randomized, parallel-group, double-blind, placebo-controlled and active-controlled multicenter trial that evaluated the safety and efficacy of Posimir in patients undergoing elective outpatient laparoscopic cholecystectomy.
Results from PERSIST showed that treatment with Posimir was not found to be statistically significantly superior to bupivacaine HCl (active control) with regard to pain intensity on movement (primary end point). As for safety, an increase in the incidence of dysgeusia was noted in the Posimir group compared with placebo. In addition, when compared with bupivacaine HCl, Posimir-treated patients were more likely to report headache and dizziness. As for local toxicity, bruising was more likely to occur in patients treated with Posimir.
Commenting on the meeting outcome, James E. Brown, President and CEO of Durect said, “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.”
Although not bound by the committees’ recommendations, the FDA does take them into consideration when making decisions on approval.
For more information visit fda.gov.