Anesthetic HTX-011 Reduces Need for Opioids in Phase 3 Studies

Eugene R. Viscusi, MD

Recently published results from 2 randomized, placebo- and active-controlled, double-blind, phase 3 clinical studies show that the experimental drug HTX-011 reduces pain intensity and the need for opioid rescue medication in post-operative patients.

The studies included patients undergoing bunionectomy (EPOCH1) and hernia repair (EPOCH2). HTX-011 achieved all primary and secondary endpoints in both studies, resulting in significant reductions in pain intensity and opioid medication use in the 72 hours after the surgery.

Specifically, the primary endpoint was pain intensity as measured by the Area Under the Curve (AUC) score from 0 to 72 hours post-surgery (AUC 0-72) compared to placebo. Key secondary goals included comparison of pain intensity by AUC 0-72 to bupivacaine solution, the amount of opioid rescue medication consumed compared to placebo in the 72 hours after surgery, the proportion of patients who did not use opioids after surgery compared to bupivacaine solution, and total opioid consumption in the 72 hours following surgery compared to bupivacaine.

This week, President Trump announced a plan that included a call for a decrease in the use of opioid medication. The plan also called for research into and development of non-addictive pain management options as alternatives to opioid prescriptions.

There is a "desperate need for effective non-opioid alternatives,” said Eugene R. Viscusi, MD, Professor of Anesthesiology and Chief of Pain Medicine in the Department of Anesthesiology at the Sidney Kimmel Medical College of Thomas Jefferson University in Philadelphia in a statement. “The phase 3 results with HTX-011 suggest it may be a promising foundation in non-opioid multimodal pain management in a wide range of surgical procedures.”

Both studies did see significant differences in pain intensity when compared to placebo or bupivacaine treatment. There was a 23% reduction in pain intensity as measured by AUC 0-72 when comparing HTX-011 to placebo in the EPOCH2 study, and a 21% reduction when compared to the bupivacaine treatment. EPOCH1 saw a 27% reduction in pain intensity as measured by AUC 0-27 compared to placebo and 18% compared to the bupivacaine solution.

A previous study of thoracic surgery has shown that post-operative opioid prescriptions can place patients at risk of becoming addicted to these medications, contributing to the country’s opioid use epidemic.

“This fast-moving epidemic affects both men and women, and people of every age,” said CDC Acting Director Anne Schuchat, M.D. in a statement. “It does not respect state or county lines and is still increasing in every region in the United States.”

HTX-011 was designed to relieve patient pain while reducing the need for opioid medications which carry the risks of abuse and addiction. Both studies saw reductions in the amount of opioid medication patients consumed after surgery.

Following bunionectomy, patients receiving HTX-011 consumed 37% less opioid medication in the 72 hours following surgery than placebo patients and 25% less opioid medication than patients receiving the standard dose of bupivacaine solution. Furthermore, 29% of patients receiving HTX-011 required no opioid medication in the 72 hours post-surgery compared to only 2% receiving placebo and 11% receiving the standard-of-care, bupivacaine solution.

Patients recovering from hernia repair surgery also consumed less medication than the other groups in the 72 hours after surgery (38% less than placebo, 25% less than bupivacaine). In this study, 51% of patients receiving HTX-011 required no opioid medication for 72 hours post-surgery compared to only 22% receiving placebo and 40% receiving the standard-of-care, bupivacaine solution.

HTX-011 was granted Fast Track Designation by the FDA in late 2017 and Heron Therapeutics, Inc. announced that it intends to submit the drug for FDA approval in the second half of 2018.