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FDA advisory committee hears Exparel data for supplemental new drug application
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The FDA Anesthetic and Analgesic Drug Products Advisory Committee began its review of the supplemental new drug application from Pacira Pharmaceuticals Inc., in which the company seeks expansion of the current Exparel (bupivacaine liposomal injectable suspension) label for infiltration to include its use as a nerve block to produce regional analgesia.
The FDA approved bupivacaine liposomal injectable suspension in Oct. 2011 with the indication for administration into the surgical site to produce postsurgical analgesia and it is currently the only FDA-approved long-acting, non-opioid analgesic, according to a briefing document Pacira provided for the meeting.
“We are proposing two changes to our current approved indication. First, a revision to our indication for infiltration to align to label with how local anesthetics are used as a field block in clinical practice,” Richard Scranton, MD, MPH, senior vice president and chief scientific officer of Pacira Pharmaceuticals, said at the meeting on Feb. 14. “Second, we are proposing adding an indication for nerve block, supported by the safety and efficacy data presented here today.”
Efficacy data
The supplemental NDA included results of four phase-3 studies in which patients received 133 mg or 266 mg of bupivacaine liposomal injectable suspension or placebo during total shoulder arthroplasty/rotator cuff repair, thoracotomy or total knee arthroplasty. The primary outcome measure was cumulative pain intensity at 48 hours and 72 hours. The secondary outcomes measures used included total opioid use, the percentage of patients who were opioid-free and the time to first opioid use.
Results of two of the studies showed bupivacaine liposomal injectable suspension was efficacious in both the upper and lower extremities, as well in both small and large nerves.
The supplemental NDA also included two single-site investigator-initiated trials in which bupivacaine liposomal injectable suspension plus bupivacaine hydrochloride (HCl) was compared with bupivacaine HCl alone in patients undergoing Dupuytren’s contracture release or scarf osteotomy for severe hallux valgus deformity. Both studies revealed improved analgesia in the use of bupivacaine liposomal injectable suspension plus bupivacaine HCl vs. bupivacaine HCl alone. There were significantly lower pain scores reported in the group treated with bupivacaine liposomal injectable suspension plus bupivacaine HCl.
“Our clinical studies have also shown the long-lasting pain relief achieved with Exparel can substantially reduce opioid use after surgery,” Scranton said. “[We] are committed to conducting post-market studies and advancing partnerships with other organizations to maximize the benefits of opioid reduction with Exparel.”
Consistent safety events
A safety database of 2,047 individuals in 29 clinical studies, of whom 531 received bupivacaine liposomal injectable suspension as a single-dose nerve block across six phase-2 or phase-3 studies, showed safety events consistent with the use of local anesthetic as a nerve block for various surgical procedures. Results revealed a similar incidence of adverse events among the bupivacaine liposomal injectable suspension and placebo groups. Nausea, pyrexia and constipation were the most common adverse events with the study drug and no additional risk of local anesthetic systemic toxicity was found. However, there was one new safety concern related to the adverse event of falls, according to background information for the meeting from Pacira Pharmaceuticals.
“To minimize the risk of falls, and based on the known effects of bupivacaine, we are proposing the precaution for our label that Exparel is not recommended for use as a femoral nerve block if early mobilization and ambulation is part of the patient’s recovery plan,” Scranton said. “However, there may be cases when early ambulation is not a clinical goal, such as lower extremity trauma, deformity correction or amputation. In these cases, a long lasting femoral nerve block with Exparel could be clinically appropriate.”
The Anesthetic and Analgesic Drug Products Advisory Committee’s review of the supplemental NDA continues Feb. 15 with FDA presentations, committee discussions and a vote on the efficacy, safety and risk-benefit profile for the expanded labeling of bupivacaine liposomal injectable suspension. – by Casey Tingle
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