Heron Therapeutics has reported positive outcome of a recent End-of-Phase 2 meeting with the US Food and Drug Administration (FDA) regarding its investigational agent, HTX-011, to prevent postoperative pain for the first 72 hours post surgery.
General agreement was reached with the FDA on the design and key elements for HTX-011’s Phase 3 program that will be required to support a New Drug Application (NDA). The program includes two pivotal Phase 3 efficacy studies in bunionectomy and hernia repair, representing a bony model and a soft tissue model, respectively.
Heron recently initiated patient enrollment in the HTX-011 Phase 3 program and anticipates completing the Phase 3 program in the first half of 2018. Heron expects to file an NDA for HTX-011 in 2018.
The Phase 3 program is designed to achieve a broad indication for the reduction in postoperative pain for 72 hours following surgery. The primary endpoints of the Phase 3 efficacy studies will be the difference in mean area under the curve (AUC) of pain intensity scores through 72 hours compared with placebo.
The first key secondary endpoints will be the difference in mean AUC of pain intensity scores through 72 hours compared with bupivacaine. Additional key secondary endpoints measuring reduction in opioid use and proportion of subjects who are opioid-free are included to support an opioid-sparing claim.
In addition to the Phase 3 efficacy studies, approximately 200 patients will be enrolled in a Phase 3 safety and pharmacokinetics study to meet the target patient numbers established by the FDA and to provide further evidence of the broad utility of HTX-011 across multiple surgical models. Importantly, the FDA noted that, beyond the agreed-upon Phase 3 studies, no additional clinical work is needed to meet the “Combination Rule” for fixed-dose combination products.
“Inadequate pain management during the first 72 hours following surgery may lead to chronic post-surgical pain and an increased risk of opioid addiction. This places a greater economic burden on the healthcare system, and it potentially results in millions of opioids flooding our communities,” said Harold S. Minkowitz, MD, Diplomat American Board of Anesthesiology, Department of Anesthesiology, Memorial Hermann Memorial City Medical Center.
“New treatments, such as HTX-011, are addressing how we can prevent, not just react to, the overuse and abuse of opioids in so many of our neighborhoods. HTX-011 provides a highly effective, non-opioid analgesic option before the problem starts. Effectively managing post-surgical pain and prioritizing treatments that can reduce the need for opioid prescriptions are critical steps toward getting ahead of the opioid epidemic.”
HTX-011 is the first and only long-acting anesthetic designed to address both postoperative pain and inflammation in a single administration at the surgical site. HTX-011 leverages meloxicam in our proprietary polymer formulation to potentiate the local anesthetic activity of bupivacaine over 72 hours.
The unique synergy of bupivacaine and meloxicam in HTX-011 has been shown to reduce pain significantly better than placebo or bupivacaine alone in three diverse surgical models: bunionectomy, hernia repair and abdominoplasty.
Final Phase 2 Results from Bunionectomy, Hernia Repair and Abdominoplasty Studies for HTX-011
As part of our End-of-Phase 2 meeting update, Heron is presenting final Phase 2 results for HTX-011 using the doses, route of administration and statistical methodology that will be used in the Phase 3 studies. These results indicate that HTX-011 has consistently demonstrated superiority over placebo and bupivacaine, the current standard-of-care, in all surgical models evaluated.
Bunionectomy: HTX-011 60 mg reduced pain through 72 hours significantly better than placebo (P=0.0003) and bupivacaine 50 mg (P=0.0166)
HTX-011’s pain reduction through 72 hours, as compared to placebo, was 24 times greater than a similar dose of bupivacaine
Hernia Repair: HTX-011 300 mg reduced pain through 72 hours significantly better than placebo (P=0.0045) and bupivacaine 75 mg (P=0.0427)
HTX-011’s pain reduction through 72 hours, as compared to placebo, was more than 4 times greater than bupivacaine
Abdominoplasty: HTX-011 400 mg reduced pain through 72 hours significantly better than placebo (P=0.0041) and bupivacaine 100 mg (P=0.0399)
HTX-011’s pain reduction through 72 hours, as compared to placebo, was more than 5 times greater than bupivacaine
The final Phase 2 results seen in bunionectomy and hernia repair correspond with the primary and first key secondary endpoints for the Phase 3 efficacy studies agreed to by the FDA.
“We are pleased to announce the positive outcome of the End-of-Phase 2 meeting for HTX-011 and the recent initiation of patient enrollment in our Phase 3 program,” said Barry D. Quart, Pharm.D., Chief Executive Officer of Heron Therapeutics.
“In bunionectomy and hernia repair, the surgical models planned for Phase 3, we have demonstrated consistent efficacy against both placebo and bupivacaine solution, the standard-of-care used for local administration in more than 11 million surgical procedures per year for postoperative pain control.”