A US Food and Drug Administration (FDA) advisory panel was split on recommending approval of bupivacaine to control post-surgical pain.
During the daylong deliberations, many of the members of the Anesthetic and Analgesic Drug Products Advisory Committee said the data presented were too complex, making them difficult to interpret.
"This was a tough decision; I felt conflicted and confused from the beginning of the meeting," said meeting chair Ronald Litman, DO, associate professor of anesthesia & pediatrics, Perelman School of Medicine, University of Pennsylvania, Pittsburgh, who voted against the drug's approval.
Several of his colleagues thought the evidence was more compelling.
"We all know this is not a magic bullet, but it's certainly better than placebo and probably better than standard bupivacaine, at least in some procedures," said Basavana Goudra, MD, clinical associate professor of anesthesiology and critical care medicine, also of the Perelman School of Medicine, who was in favor of approval.
Over 50 million surgical procedures take place in the United States every year. Up to 70% of patients experience moderate to severe pain after surgery, with pain being most severe during the first 72 hours. Poorly controlled pain can have negative outcomes and delay recovery.
Up to 90% of surgical patients receive opioids for pain management, but these can have significant adverse events, including nausea, vomiting, constipation, sedation, and respiratory depression.
Fraught History
The new drug has been in the regulatory works for some time. A new drug application for Posimir was originally submitted in April 2013 but did not receive the go-ahead at that time because of a number of concerns.
The FDA issued a Complete Response Letter (CRL). The applicant then filed an appeal, which was denied.
The company submitted a Complete Response to the CRL that addressed issues pertaining to safety and inconsistent efficacy findings across surgical models and included information from a new trial. The advisory committee met to discuss this resubmission.
Posimir is an investigational extended-release formulation of bupivacaine, which is directly administered into a surgical site. Bupivacaine, an amide-type local anesthetic widely used in surgical practice, is the active ingredient, but the product also contains sucrose acetate isobutyrate and benzyl alcohol.
The new product is typically administered as a single dose through a needleless syringe into the surgical incision. Following administration, it releases bupivacaine at a stable rate, ranging from 10-20 mg/hour over the first 2 days and declining to 5 mg/hour or less by the end of the third day.
The company completed six efficacy studies in a range of surgical models that met FDA criteria for adequacy. All studies were randomized, double-blind, and multicenter, with a parallel-group design.
