Statistically Significant and Clinically Meaningful 52% Reduction in Opioid Consumption After Discharge Through Two Weeks Following Surgery
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Early Reductions in Pain at Rest and Pain with Activity Lasted Continuously Through Two Weeks
SAN FRANCISCO–(BUSINESS WIRE)–Concentric Analgesics, Inc., a clinical-stage biopharmaceutical company focused on developing and commercializing novel, non-opioid pain therapeutics, today announced additional positive results from its recently completed Phase 2 clinical trial of vocacapsaicin (CA-008), a first-in-class, non-opioid therapeutic with FDA Breakthrough Therapy Designation. The study, conducted in 187 patients undergoing total knee arthroplasty (“TKA”), evaluated the effects on reported pain, opioid consumption, safety and pharmacokinetics of vocacapsaicin over 28 days.
The company previously reported top line results from this Phase 2 study showing vocacapsaicin, administered once during surgery at a dose of 36 mg, achieved statistically significant and clinically meaningful reductions in pain at rest, pain with activity and opioid use for the first 7 days following surgery. Vocacapsaicin produced analgesia without sensory numbness or motor weakness. Additional analyses now confirm vocacapsaicin’s early therapeutic benefits lasted continuously through two weeks.
The new analyses show that patients receiving vocacapsaicin 36 mg used fewer opioids and stopped taking opioids sooner. The reductions in both the amount and duration of opioid use were achieved even though all patients received standard of care, multi-modal, non-opioid analgesics. The 30% reduction in mean opioid consumption observed during hospitalization from 0-96h (p<0.0001) increased to a 52% reduction in opioid consumption after discharge from 96h-Day 15 (D15) (p=0.0063). The trend towards earlier discontinuation of opioids observed during hospitalization also persisted after discharge through two weeks.
The reductions in pain at rest and with ambulation for the 36 mg dose of vocacapsaicin continued throughout the two weeks after surgery. The 17% reduction in mean pain at rest AUC 0-96 (p=0.0012) persisted at 15% from 0-D15 (p=0.03). The 21% reduction in mean pain with ambulation AUC 0-96 (p=0.0006) persisted at 14% from 0-D15 (p=0.04).
“These results are impressive,” said Alparslan Turan, MD, Professor of Anesthesiology at Lerner College of Medicine of Case Western University and Vice Chair of the Department of Outcomes Research at the Cleveland Clinic, the largest single-center clinical research group in the field of anesthesiology. “The products that are out there show an effect for 1-3 days, but nothing has shown a continuous benefit for 2 weeks, in particular for the longer-term reduction of opioid use. If this drug becomes available, I believe it will be widely used.”
According to the Centers for Disease Control and Prevention, long-term opioid use often begins with treatment of acute pain. The probability of long-term opioid use increases most sharply in the first days of therapy, particularly after 5 days of opioid use.
Dr. Turan further stated, “Vocacapsaicin’s reduction in pain for two weeks merits further study for its ability to better manage acute pain throughout the postsurgical period, including physical therapy and into a return to normal activities. It is known that better early postsurgical pain management translates into fewer problems with chronic pain.”
“Today’s results validate the potential for vocacapsaicin to become an innovative non-opioid treatment option for clinicians,” said John Donovan, MD, anesthesiologist, Co-founder & Chief Scientific Officer of Concentric Analgesics. “Our success in TKA, an important and highly relevant surgical model that has proven challenging for other locally-delivered analgesics, represents an important step towards the goal we set from day 1 – to develop a best-in-category therapeutic that can improve patient care.”
Based on the positive Phase 2 dose-ranging study results in two surgical models – TKA and bunionectomy – the company has identified the effective dose level of vocacapsaicin. An End of Phase 2 Meeting with the FDA is scheduled in April 2021. Based on the available Phase 2 results and discussions with the FDA, the company will evaluate additional surgical models while finalizing plans for Phase 3.
“Today’s TKA results, combined with the comparable results reported from our previous Phase 2 bunionectomy study, enable us to move forward expeditiously to our End of Phase 2 meeting with the FDA and share our plans for Phase 3,” said Susan Kramer, DrPH, Executive Vice President of Development of Concentric Analgesics. “All key elements of our development program, including nonclinical and CMC activities, are progressing on plan toward our NDA submission goal.”
Study Design
The randomized, double-blind, placebo-controlled, dose-finding study enrolled 187 patients undergoing total knee arthroplasty and compared the safety and efficacy of vocacapsaicin to a standard of care, active control. During surgery, all patients received a standard of care that included spinal anesthesia, ketorolac, acetaminophen, and ropivacaine (joint infiltration, femoral nerve and IPACK blocks). The study was comprised of two arms receiving vocacapsaicin 36 mg (n=61) and 60 mg (n=62) and a standard-of-care, placebo control arm (n=64) with active opioid rescue. Vocacapsaicin, a prodrug of capsaicin, was administered via infiltration to the surgical site. The primary efficacy endpoint of the Phase 2 study was reduction in pain at rest (AUC) from 12-96h, with key secondary endpoints including reduction in pain and opioid consumption over 0-96h and over two weeks (0-D15) post-surgery.
Efficacy Results Summary
Patients were evaluated for pain intensity using the standard Numerical Rating Scale (NRS), as measured by the area under the curve (AUC) during specified intervals. Key secondary endpoints included opioid consumption, pain intensity at rest and with ambulation (all collected over 2 weeks), readiness for early discharge, along with standard safety measures and PK sample collections.
Further analysis of vocacapsaicin 36 mg showed additional statistically significant and clinically meaningful results, including:
- 52% reduction in opioid consumption 96h-D15 (p=0.0063)
- 35% reduction in opioid consumption 0-D15 (p<0.0001)
- 15% reduction in pain at rest AUC 0-D15 (p=0.03)
- 14% reduction in pain with ambulation AUC 0-D15 (p=0.04)
Concentric previously reported the following results:
- 18% reduction in pain at rest AUC 12-96h (p=0.0004) – study primary endpoint
- 17% reduction in pain at rest AUC 0-96h (p=0.0012)
- 15% reduction in pain at rest AUC 0-168h (p=0.01)
- 21% reduction in pain with ambulation AUC 0-96h (p=0.0006)
- 17% reduction in pain with ambulation AUC 0-168h (p=0.0072)
- 30% reduction in opioid consumption 0-96h (p<0.0001)
- 31% reduction in opioid consumption 0-168h (p<0.0001)
- An increase in the proportion of patients able to ambulate 100 feet at 72h (90% vs 63%, respectively, p=0.0003)
In this dose-finding study, the overall response observed with vocacapsaicin 36 mg was consistently better than that observed with the 60 mg dose.
Safety Results Summary
The safety profile of vocacapsaicin was evaluated for 28 days following surgery in the standard research manner by serial assessments of adverse events, vital signs, physical examination, surgical wound healing and laboratory testing. Vocacapsaicin generally appeared safe and well-tolerated. All parameters appeared consistent with a benign safety profile compared to the control group, with no local or systemic safety concerns identified.
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, approximately 50,000 Americans died from opioid overdoses in 2018 – 30% more than the total number of deaths from automobile accidents. New approaches for preventing this insidious disease are imperative, including in the postsurgical setting, which can be an unsuspecting 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 in 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 a week or more. Vocacapsaicin has received both Fast Track Designation (2017) and Breakthrough Therapy Designation (2018) from the FDA.
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. Vocacapsaicin is the company’s Phase 3-ready lead product candidate for postsurgical pain. Concentric has two additional active programs for multiple 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.
Contacts
Frank Bellizzi
Chief Executive Officer
Concentric Analgesics, Inc.
frank@concentricanalgesics.com