RESEARCH & RELATED Other Project Information Project Summary/Abstract This proposal is entitled ?The long-term reduction of pain and opioid usage following mastectomy and tissue expander/implant surgery with a single administration of brivoligide, a non-opioid, disease-modifying drug candidate.? Brivoligide is a non- opioid drug candidate that can alter the course of postoperative pain for patients most likely to suffer increased pain and utilize more opioids following surgery. These patients are identified in advance of surgery using the well-validated Pain Catastrophizing Scale (PCS). A single administration of brivoligide at the time of surgery can reduce acute postoperative pain in these patients by 30 to 40% beyond what can be achieved with current standard of care for at least 28 days and reduce opioid utilization by 40% over a three-month period following surgery, an amount equal to more than 90 opioid tablets (5 mg hydrocodone) per patient. Based on the patient population treatable by brivoligide, this could translate to a reduction of up to 360 million tablets in the US annually. Brivoligide addresses the objective of the FOA to prevent and reduce opioid use disorder (OUD) by reducing the need for opioid analgesia and preventing the escalation of opioid dosing in patients at greater risk of using more opioids following surgery. To achieve regulatory approval of brivoligide with a broad indication for the reduction of postoperative pain in this patient population, the FDA requires evidence of brivoligide efficacy in one orthopedic and one soft-tissue model of postoperative pain. Brivoligide has been studied in three Phase 2 trials in patients undergoing total knee arthroplasty, an orthopedic model of postoperative pain. Grant funding will allow studying brivoligide in mastectomy, a soft-tissue surgery model suitable to detect long-term pain and opioid reduction benefits. The UG3 portion of the grant will specifically fund a 126-subject, randomized, double-blind, placebo-controlled Phase 2 trial in patients undergoing mastectomy with immediate tissue expander or implant placement. Following an End-of- Phase 2 meeting with the FDA, the UH3 portion will fund a subsequent pivotal Phase 3 mastectomy trial. The Phase 2 and 3 studies will focus on both pain reduction and opioid reduction in subjects with elevated scores on the PCS.
RESEARCH & RELATED Other Project Information Project Narrative Postoperative pain remains a significant clinical problem that is largely managed with opioid-based therapies. With a single administration at the time of surgery, Adynxx's brivoligide can reduce postoperative pain by up to 40% on top of standard of care for at least 28 days and reduce postoperative opioid utilization by 40% over a three-month period in a readily-identifiable group of patients with the greatest risk of experiencing increased pain and escalating opioid use following knee replacement surgery. The goal of this research project is to rapidly advance brivoligide into a Phase 2 clinical trial of patients undergoing mastectomy in order to widen the range of surgical procedures addressable by brivoligide, provide a much needed non-opioid therapy for postoperative pain, reduce the need for postoperative opioid analgesia and prevent the escalation of opioid dosing in high-risk patients.
