Tarius SAC Tracker®
Background Analysis: US FDA Advisory Committee to Review Proposed Expanded Use for Pacira Pharmaceuticals’ Exparel – FEB 14-15, 2018 (AADPAC)
The US FDA has scheduled a meeting of the Anesthetic and Analgesic Drug Products Advisory Committee (AADPAC) for Wednesday (afternoon) and Thursday, February 14-15, 2018. The Committee will discuss a supplemental new drug application (sNDA) for Exparel (bupivacaine liposomal injectable suspension), submitted by Pacira Pharmaceuticals, Inc. (Pacira), to produce local analgesia and as a nerve block to produce regional analgesia.
Description of Indication
The current indication for Exparel is:
EXPAREL is a liposome injection of bupivacaine, an amide local anesthetic, indicated for single-dose infiltration into the surgical site to produce postsurgical analgesia.
The proposed new use is to produce local analgesia and as a nerve block to produce regional analgesia.
Description of Drug Class
Bupivacaine is an analgesic that is related chemically and pharmacologically to amide-type local analgesics. It is a homologue of mepivacaine and is related chemically to lidocaine.
Description of Product
Exparel is an aqueous suspension of liposomes that contain bupivacaine. After injection of Exparel into soft tissue, bupivacaine is released from the liposomes over a period of time. It is intended for single-dose administration only. The recommended dose is based on the size of the surgical site, the volume required to cover the area, and individual patient factors that may impact the safety of an amide local anesthetic. The currently recommended maximum dose is 266 mg (20 mL).
Clinical Trials of Proposed Indication
According to Pacira, eight studies support the proposed new use. The company has reported that, in total, 570 subjects received a dose of Exparel ranging from 2 mg to 310 mg. The primary bases of the sNDA is a Phase 3 study of Exparel in patients receiving femoral nerve block for total knee arthroplasty (lower extremity) and a Phase 3 study of Exparel in patients receiving brachial plexus block for shoulder surgeries (upper extremity). Pacira has noted that the sNDA also includes safety and pharmacokinetic data through 120 hours, in addition to data from two investigator-initiated studies that provide additional experience in smaller, peripheral nerve block settings.
US Regulatory Background
April 6, 2018 – PDUFA date
October 18, 2017 – Pacira announced the FDA’s acceptance of the sNDA resubmission (022496/S-009)
December 14, 2015 – The FDA approved a separate sNDA (022496/S-019) that, among other changes, resulted in the removal of the following key labeling statement: “EXPAREL has not been demonstrated to be safe and effective in other procedures.” The FDA previously had required this statement in reference to procedures other than bunionectomy and hemorrhoidectomy.
October 13, 2015 – In a rare move, the FDA rescinded a Warning Letter that was issued to Pacira on September 22, 2014. The Warning Letter objected to Pacira’s marketing materials that promoted Exparel for surgeries other than bunionectomy and hemorrhoidectomy. The Warning Letter also objected to Pacira’s general claims about Exparel’s ability to control pain for up to 72 hours. In a letter to Pacira, dated December 14, 2015, the FDA stated (in part):
In a recent review of the Warning Letter, the FDA-approved labeling for EXPAREL, and related materials, FDA determined that different statements in various parts of the approved labeling created ambiguity with respect to the scope of the approved indication. Ultimately, however, the use described in EXPAREL’s Indications and Usage statement broadly referred to “surgical site[s]” and was not limited to bunionectomy and hemorrhoidectomy procedures. Based on the plain language of the Indications and Usage section of the full prescribing information, as well as the clinical trials submitted in support of that approval, FDA determined that the indication approved in 2011 was not limited to bunionectomy and hemorrhoidectomy procedures.
March 2, 2015 – Exparel announced receipt of a Complete Response Letter from the FDA, a rejection of a proposed sNDA, which was seemingly sNDA 022496/S-009.
October 28, 2011 – Initial NDA approval
Tarius will send a Briefing Summary after briefing materials are posted to FDA’s website (typically within 2 days of the meeting). This report will provide a summary of the FDA and the Sponsor’s briefing materials.
Tarius will send a Results Wire soon after the meeting. This report will include the voting outcomes, if applicable, and key outcomes of the discussion.
METADATA: Sponsor: Pacira Pharmaceuticals, Inc. Drug Name: bupivacaine liposomal injectable suspension Drug Class: amide local anesthetic Indication: local and regional analgesia
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DISCLAIMER: The information in this document is for informational purposes only. The SAC Tracker Background Analysis contains information from publicly available sources, including FDA, sponsor, scientific, and clinical websites. Tarius A/S assumes no liability for any inaccurate or incomplete information, or for any actions taken in reliance thereon. © Tarius A/S. All rights reserved.