Concentric Analgesics Announces Peer-Reviewed Publication of Positive Phase 2 Clinical Data in ANESTHESIOLOGY

Vocacapsaicin is the First Investigational Therapeutic to Show More than Seven Days of Postsurgical Pain Relief and Earlier Cessation of Opioids

Advanced Preparations for Phase 3 Vocacapsaicin Trials are Underway

July 24, 2024

Concentric Analgesics, Inc., a clinical-stage biopharmaceutical company developing novel, non-opioid pain therapeutics, today announced publication of a multicenter, randomized clinical trial evaluating vocacapsaicin on the cover of the August 2024 issue of ANESTHESIOLOGY, the highest impact journal in the specialty. Results showed that a single dose of vocacapsaicin significantly reduced pain and opioid use for at least one week after bunionectomy, the most commonly studied model to assess and validate analgesic benefit for postsurgical pain.

Vocacapsaicin is an innovative, water-soluble prodrug of capsaicin. Vocacapsaicin rapidly releases capsaicin at the surgical site after a single local administration during surgery which triggers activation of the TRPV1 receptor on pain-specific nerves. TRPV1 activation is known to produce analgesia that lasts for weeks to months without causing sensory numbness or motor weakness. This is a highly differentiated mechanism of action from local anesthetics, such as bupivacaine, which are short-acting and produce sensory numbness and motor weakness.

In the Phase 2 study, 147 patients were randomized to receive one of three doses of intraoperative locally administered vocacapsaicin (0.30, 0.15 or 0.05 mg/ml) or placebo. All patients received identical perioperative analgesia. The prospective objective was to test the therapeutic benefit of the 0.30 mg/mL dose.

Results of prespecified primary and key secondary endpoints for the 0.30 mg/ml group, compared to placebo control group, showed:

  • 33% reduction in pain at rest during 0–Day 5 (p=0.005)

  • 37% reduction in pain at rest during 0–Day 8 (p=0.004)

  • 50% reduction in opioid consumption during 0-Day 5 (p=0.002)

  • Five times as many patients receiving vocacapsaicin never needed any postoperative opioid analgesia compared to control (26% vs 5%, respectively, p=0.025).

In addition, 

  • 100% of the vocacapsaicin group stopped opioids by Day 5 while 16% of the control group still required opioid analgesia at that time (p=0.001);

  • 8% in control group continued to need opioids at Day 15

  • The analgesic effect of vocacapsaicin was persistent and consistently evident on each day throughout the two weeks following surgery

  • A clear dose response was documented

  • Vocacapsaicin appeared safe and well tolerated with no differences between groups in any safety parameter. 

The risk of persistent opioid use, a known risk factor for opioid dependence and abuse, increases most sharply in the initial days of treatment, particularly for patients who continue taking opioids after 5 days. 

Lead author, Steven L. Shafer, MD, Professor Emeritus, Stanford University School of Medicine and adviser to Concentric said, “This is the first demonstration of a single intra-operative injection leading to earlier cessation of opioids after surgery. By targeting TRPV1 receptors, vocacapsaicin eclipses the duration of pain relief possible from local anesthetic formulations.”

In his accompanying editorial, A Spicy New Treatment for Postoperative Pain, David Clark, MD, PhD, Professor of Anesthesiology, Perioperative and Pain Medicine, Stanford University stated, "Fundamental advancements in our field do not occur every day, so it is particularly exciting when early reports of innovative new treatments are published. The potential value of this type of treatment is enormous.”

Eske K. Aasvang, MD, Professor of Anaesthesiology, Rigshospitalet Copenhagen and Chairman of the Danish Medicines Board’s National Guideline on Follow-up After Opioid Prescription stated, “The most important finding in the vocacapsaicin studies by Concentric Analgesics is the reduced opioid consumption and, of particular significance, the earlier cessation. This drug gives us hope for fewer long-term opioid users and less of the all too frequent opioid-related severe adverse events including abuse and death."

Michael D. Maloney, MD, Dean’s Professor of Orthopaedics, Chief of the Division of Sports Medicine, and Medical Director of the Ambulatory Surgery Center at University of Rochester Medical Center said, “In addition to these data, I have been equally impressed by the Phase 2 data on the use of vocacapsaicin during total knee arthroplasty published in abstracts. Orthopedic surgeons want an easy-to-use, intra-operative non-opioid analgesic that can reduce pain during the full postsurgical recovery period, including rehabilitation.”

“We are pleased that our Phase 2 study merited the cover of ANESTHESIOLOGY, along with the accompanying editorial, which we believe validates vocacapsaicin’s extraordinary potential clinical impact,” said Frank Bellizzi, chief executive officer of Concentric Analgesics. “Our plans to begin Phase 3 studies are largely completed and we remain deeply committed to bringing this innovative new treatment to patients and clinicians as quickly as possible.”

Link: https://pubs.asahq.org/anesthesiology/article/141/2/250/140092/Safety-and-Efficacy-of-Vocacapsaicin-for

About Opioid Addiction & Postsurgical Pain
Opioid addiction in the United States has reached epidemic proportions, destroying families, lives and communities throughout the country. According to the Centers for Disease Control and Prevention, over 90,000 Americans died from opioid overdoses in 2020 – more than the annual total number of deaths from automobile accidents and gun deaths combined. New approaches for preventing this insidious disease are imperative, including in the postsurgical setting, which can be a significant gateway to prescription pain medicine abuse and beyond. A 2016 US News & World Report revealed that one in 10 patients report becoming addicted or dependent on opioids following surgery. With more than 100 million surgeries performed in the U.S. in 2017, 30 million of which required postsurgical pain management with products that were not over-the-counter (OTC) drugs, the mandate to develop safe and effective non-opioid alternatives is clear.

About Vocacapsaicin (CA-008)
Concentric Analgesics’ lead product candidate for postsurgical pain is a first-in-class prodrug therapeutic that rapidly converts to capsaicin, a potent TRPV1 agonist. Unlike local anesthetics, capsaicin selectively desensitizes pain-conducting nerve fibers without producing sensory numbness or motor weakness. Vocacapsaicin, injected as an aqueous solution during surgery, has the potential to reduce, and in some patients, eliminate the need for opioids in the postsurgical recovery period and provide clinically meaningful pain relief for two weeks. Vocacapsaicin has received both Fast Track Designation (2017) and Breakthrough Therapy Designation (2018) from the U.S. Food and Drug Administration.

About Concentric Analgesics
Concentric Analgesics is a clinical-stage, biopharmaceutical company focused on developing and commercializing novel, non-opioid pain therapeutics. The company’s portfolio of proprietary products is designed to provide long-lasting, selective pain relief after a single local administration. The company is initiating Phase 3 studies for vocacapsaicin, its lead product candidate for postsurgical pain. Concentric has two additional active programs for indications with significant unmet medical need: osteoarthritis pain and chronic refractory pain. For more information, please visit the company’s website at: www.concentricanalgesics.com.

For More Information:
Frank Bellizzi
Chief Executive Officer
Concentric Analgesics, Inc.
frank@concentricanalgesics.com

Susan Kinkead
susan@kinkeadcomm.com
415-509-3610