Concentric Analgesics Publishes Positive Phase 2 Data in ANESTHESIOLOGY

Concentric Analgesics, Inc., a clinical-stage biopharmaceutical firm, recently published results from a multicenter, randomized clinical trial on vocacapsaicin in the August 2024 issue of ANESTHESIOLOGY, a leading journal in the field. The study revealed that a single dose of vocacapsaicin significantly lessened pain and reduced the need for opioids for at least one week following bunionectomy surgery, a common model used to study and confirm pain relief effectiveness in postsurgical settings.

Vocacapsaicin, an innovative, water-soluble prodrug of capsaicin, releases capsaicin at the surgical site after a single local application during surgery. This release activates the TRPV1 receptor on pain-specific nerves, leading to pain relief that can last for weeks to months without causing sensory numbness or motor weakness. This mechanism of action distinctly differs from that of local anesthetics like bupivacaine, which are short-acting and can result in sensory numbness and motor weakness.

In the Phase 2 study, 147 patients were randomized to receive one of three doses of vocacapsaicin (0.30, 0.15, or 0.05 mg/ml) or a placebo, with all patients receiving the same perioperative pain management. The primary goal was to assess the 0.30 mg/ml dose's therapeutic benefit.

Key findings for the 0.30 mg/ml group, compared to the placebo group, included:
- A 33% reduction in pain at rest from Day 0 to Day 5 (p=0.005)
- A 37% reduction in pain at rest from Day 0 to Day 8 (p=0.004)
- A 50% reduction in opioid use from Day 0 to Day 5 (p=0.002)
- Five times more patients in the vocacapsaicin group did not need postoperative opioid analgesia compared to the control group (26% vs 5%, p=0.025)

Additionally, all patients in the vocacapsaicin group discontinued opioid use by Day 5, while 16% of the control group still required opioids at that time (p=0.001). Notably, 8% of the control group continued to need opioids at Day 15. The analgesic effect of vocacapsaicin was consistent and evident each day throughout the two weeks post-surgery, and a clear dose-response relationship was observed. Vocacapsaicin appeared safe and well-tolerated, with no differences in safety parameters between the groups.

The risk of persistent opioid use, which can lead to dependence and abuse, increases significantly in the early days of treatment, especially for patients using opioids beyond five days. Steven L. Shafer, MD, Professor Emeritus at Stanford University School of Medicine and an adviser to Concentric, noted, "This is the first demonstration of a single intra-operative injection leading to earlier cessation of opioids after surgery. By targeting TRPV1 receptors, vocacapsaicin extends the duration of pain relief beyond that possible with local anesthetics."

David Clark, MD, PhD, Professor of Anesthesiology at Stanford University, commented, "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 at Rigshospitalet Copenhagen, emphasized the reduction in opioid consumption and earlier cessation as crucial findings, stating that it offers hope for fewer long-term opioid users and reduced opioid-related adverse events, including abuse and death.

Michael D. Maloney, MD, from the University of Rochester Medical Center, highlighted the promising Phase 2 data on the use of vocacapsaicin during total knee arthroplasty. He pointed out that orthopedic surgeons seek an easy-to-use, intra-operative non-opioid analgesic for reducing pain throughout the postsurgical recovery period, including rehabilitation.

Frank Bellizzi, CEO of Concentric Analgesics, expressed satisfaction that their Phase 2 study was featured on the cover of ANESTHESIOLOGY, stating, "We believe this validates vocacapsaicin’s extraordinary potential clinical impact. We are committed to bringing this innovative new treatment to patients and clinicians as quickly as possible." The company plans to initiate Phase 3 studies soon.