Sustained-release gel for multi-day control of postoperative pain

Principal Investigator: Overstreet, Derek J. AbstractSonoran Biosciences, Inc.SBIR PA-21-259: Phase IAbout 14 million surgeries annually in the United States are associated with moderate-to- severe postoperative pain lasting at least three days at rest. Pain has been reported to be one of the most common reasons for delayed discharge following inpatient procedures and for unplanned hospital admissions following outpatient procedures. Treatment of postoperative pain presents a challenging scenario for clinicians because it is resource-intensive and frequently involves opioid medications which are associated with adverse effects. Moreover, poorly managed pain leads to patient suffering and increased risks of complications.Current best practices support the use of multimodal analgesia regimens which rely on multiple classes of drugs to offset the need for opioids. Local anesthetics are a critical component of multimodal analgesia because they can provide a potent reduction of pain in a local area while having a favorable safety profile. Unfortunately, local anesthetic molecules only remain active for up to eight hours and available extended-release products have limited efficacy beyond 12-24 hr postoperatively. The market leader is Exparel (liposomal bupivacaine), which is on pace to reach $500 million in sales in 2021. There remains a significant need and commercial opportunity for a local anesthetic that provides analgesia for at least three days, which would carry over into the home setting, potentially enabling patients to be discharged safely without opioid prescriptions.We have developed a proprietary sustained-release carrier, SB Gel, which can be mixed with the local anesthetic bupivacaine at the time of use and applied as an aqueous solution that forms a soft gel in the surgical site. SB Gel provides diffusion-based release of bupivacaine over multiple days and dissolves in vivo in about three weeks. In a pig skin and muscle incision model, bupivacaine-loaded SB Gel provided analgesia lasting for 120 hours. Significantly greater force at the incision was tolerated in sites receiving SB Gel + bupivacaine compared to those receiving Exparel at 24, 48, 72, 96, and 120 hours postoperatively.We now propose to complete a Phase 1 project to establish the feasibility of bupivacaine- loaded SB Gel as the best-in-class extended-release local anesthetic. In Aim 1, we will study the dose response of SB Gel + bupivacaine, compare the effectiveness of SB Gel + bupivacaine against all of the FDA-approved extended-release local anesthetics, and evaluate effects on wound healing. In Aim 2, we will evaluate safety, including systemic toxicity, systemic exposure to bupivacaine, and toxicity to muscle and peripheral nerves. Successful completion of the project will result in readiness for scaled-up manufacturing and future IND-enabling toxicology studies.