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

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.”

The paper, editorial and supplemental infographics are available online: https://pubs.asahq.org/anesthesiology/article/141/2/250/140092/Safety-and-Efficacy-of-Vocacapsaicin-for

Opioid Use and Abuse After Painful Surgery

Effective management of pain after surgery remains an unmet medical need. More than 30 million surgeries are performed in the U.S. annually that require prescription drugs for pain management. Oral opioid analgesics remain an integral part of postsurgical pain management despite common side effects, safety concerns, and the risk of persistent opioid use which can lead to abuse and beyond. According to the Centers for Disease Control and Prevention, more than 80,000 Americans died from opioid overdoses in 2022 – more than the annual total number of deaths from automobile accidents and gun deaths combined.

About Vocacapsaicin (formerly CA-008)

Concentric Analgesics’ lead product candidate for postsurgical pain is a first-in-class prodrug therapeutic that rapidly converts to capsaicin, a potent and well-studied TRPV1 agonist. Unlike local anesthetics, capsaicin selectively desensitizes pain-conducting nerve fibers. Vocacapsaicin has the potential to reduce or even 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 and Breakthrough Therapy Designation from the US 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 planning Phase 3 studies for vocacapsaicin, its lead product candidate for postsurgical pain. Concentric has two additional programs for osteoarthritis pain and chronic refractory pain. For more information, please visit: www.concentricanalgesics.com.

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