Phase 3 Trial Results Lead to FDA Approval of Expanded Indications for Exparel

The FDA has approved a supplemental new drug application (sNDA) to expand the indication for bupivacaine liposome injectable suspension (Exparel; Pacira BioSciences, Inc.) for use in adult patients as an adductor canal block and a sciatic nerve block in the popliteal fossa. Exparel was initially approved in 2011 for single-dose infiltration into a surgical site, and has since been administered to more than 4 million patients in the post-marketing setting since the approval, according to Pacira.

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“We are thrilled that today’s approval offers clinicians and patients another option for achieving long-lasting non-opioid pain control with Exparel and an increased ability to transition procedures to the ambulatory environment,” Dave Stack, chief executive officer and chairman of Pacira BioSciences, said in a press release. “In line with our corporate mission to provide a non-opioid to as many patients as possible, this new indication provides additional flexibility in the use of Exparel as a regional analgesic for more than 3 million lower extremity procedures annually, further increasing the utility of Exparel for major orthopedic procedures.”

Surgeons use an adductor canal block for anesthesia and analgesia to perform operations on the knee, medial lower leg, and ankle. A sciatic nerve block in the popliteal fossa is administered to provide anesthesia and analgesia for use in medical procedures on the foot, ankle, Achilles tendon, and other parts of the lower leg.

The regulatory action was supported by a pair of randomized, double-blind, active-controlled, multicenter Phase 3 studies analyzing the efficacy, safety, and pharmacokinetics of Exparel compared with bupivacaine HCl.

The first study analyzed Exparel for use as a single-dose adductor canal block and the other trial study analyzed it for use as a single-dose sciatic nerve block in the popliteal fossa.

In the trial evaluating Exparel as an adductor canal block, investigators compared its efficacy when admixed with bupivacaine HCl for postsurgical analgesia in patients receiving primary unilateral total knee arthroplasty compared with bupivacaine HCl. Investigators randomly assigned 166 patients 1:1 to receive either 10 mL of Exparel admixed with 10 mL 0.5% bupivacaine HCl or 10 mL 0.5% of bupivacaine HCl mixed with 10 mL normal saline. Patients were also administered 15 mL of 0.25% bupivacaine HCl infused between the popliteal artery and capsule of the knee block.

The primary endpoint of the trial was area under the curve of the Numerical Rating Scale pain intensity scores from 0 to 96 hours following surgery, with secondary endpoints that included total postsurgical opioid consumption from 0 to 96 hours. Researchers conducted the second trial assessing Exparel as a single-dose sciatic nerve block in the popliteal fossa in two parts, with the first part finished and evaluated prior to the initiation of enrollment in the second part.

Researchers randomly assigned 185 patients in the trial, with 66 patients in Part A who were undergoing a bunionectomy randomized 1:1:1 to receive a sciatic nerve block in the popliteal fossa with a single dose of Exparel either at 266 mg, 133 mg, or bupivacaine HCl 20 mL 0.25%.

Another 119 patients undergoing bunionectomy were randomly assigned 1:1 to receive a sciatic nerve block in the popliteal fossa with a single dose of Exparel 133 mg or bupivacaine HCl 20 mL 0.25%.

Patients across both parts received a Mayo field block with 20 mL 0.5% bupivacaine HCl following administration of Exparel in the operating room immediately before surgery. The study’s primary endpoint was the area under the curve in the Numerical Rating Scale pain intensity scores from 0 to 96 hours with Exparel compared to bupivacaine HCl following surgery. The trial’s secondary endpoints included total postsurgical opioid consumption from 0 to 96 hours with Exparel compared with bupivacaine HCl and percent opioid-free from 0-96 hours.

Exparel achieved the primary endpoints in both Phase 3 trials by showing a statistically significant drop in cumulative pain scores from 0 to 96 hours vs bupivacaine HCl. Further, Exparel reached the threshold of statistical significance in the secondary endpoint of decreased postsurgical opioid consumption. In addition, in the trial assessing its use as a sciatic nerve block in the popliteal fossa, the drug showed statistical significance in the percentage of opioid-free patients.

In terms of safety, Exparel demonstrated a safety profile consistent with bupivacaine HCl. In the press release, Pacira announced the submission of the full results from both studies for publication in a peer-reviewed journal.

“The addition of these new blocks, coupled with the previously approved interscalene brachial plexus nerve block and the ability to utilize Exparel as a fascial plane block provides clinicians with a wide array of applications to treat postsurgical pain with long-lasting, non-opioid analgesia via a single dose administration,” said Jeffrey Gadsden, MD, chief of Orthopaedic, Plastic, and Regional Anesthesiology and professor of Anesthesiology at Duke University School of Medicine, in the release. “Enhanced recovery protocols built around Exparel regional and fascial plane blocks continue to play a critical—and expanding—role in achieving increased clinician and patient preference to avoid opioids and achieve same-day discharge when appropriate.”

Reference

Pacira Announces FDA Approval of Expanded EXPAREL Label to Include Two Additional Nerve Block Indications. Pacira BioSciences, Inc. News release. Published November 11, 2023. Accessed November 13, 2023.