Zynrelef (bupivacaine/meloxicam ER) / Heron Therapeutics - LARVOL DELTA

Nanotechnology for pain management in orthopedic surgery. (PubMed, World J Orthop) - "This narrative review evaluated the potential of nanotechnology platforms (DepoFoam bupivacaine®, DepoDur®, Exparel®, Zynrelef®, NeuroCuple™) in the control of postoperative pain following orthopedic procedures...All EREM dosages diminished the mean fentanyl usage vs placebo and delayed the median time to first dose of fentanyl...Opioid consumption was reduced by 37% in the Zynrelef® PR cohort vs 25% in the bupivacaine HCl cohort. In individuals experiencing total knee arthroplasty and total hip arthroplasty, the use of a nanotechnology-based NeuroCupleTM device diminished postoperative pain at rest by 34% and reduced pain with movement by 18%."

Journal • Review • Anesthesia • Orthopedics • Pain

Outcomes for Incisional Bupivacaine and Meloxicam Extended-Release Solution Compared to Epidural Analgesia in Laparoscopic Colorectal Surgery - A Retrospective Case Control Study. (PubMed, J Gastrointest Surg) - No abstract available

Journal • Retrospective data • Infectious Disease

Zynrelef Versus Adductor Canal Block (clinicaltrials.gov) - P4 | N=120 | Not yet recruiting | Sponsor: University of Miami

New P4 trial • Immunology • Orthopedics • Osteoarthritis • Pain • Rheumatology

Bupivacaine-Meloxicam Extended-Release Solution Compared with a Standard Periarticular Injection in Primary Total Knee Arthroplasty: A Randomized Clinical Trial Showing Similar Efficacy in Postoperative Analgesia. (PubMed, J Bone Joint Surg Am) - "This randomized clinical trial demonstrated similar analgesia with a bupivacaine-meloxicam ER solution and a standard periarticular injection up to 72 hours after primary TKA. Cost, reimbursement, and convenience may ultimately prove to be more important than analgesic differences when choosing between these 2 effective options for managing postoperative pain."

Clinical • Journal • Immunology • Orthopedics • Osteoarthritis • Pain • Rheumatology

ZYNRELEF for Pain Management in Total Knee Arthroplasty (clinicaltrials.gov) - P4 | N=242 | Recruiting | Sponsor: Baptist Health South Florida | Trial completion date: Apr 2026 ➔ Dec 2027 | Trial primary completion date: Apr 2025 ➔ Oct 2027

Trial completion date • Trial primary completion date • Immunology • Orthopedics • Osteoarthritis • Pain • Rheumatology

A Randomized Controlled Trial for Dual-Agent Local Analgesic in Sling Surgery. (PubMed, Urogynecology (Phila)) - "Use of Zynrelef during retropubic sling surgery does not reduce narcotic use in the first 3 days postoperatively. Patients can be reassured that pain and narcotic use after surgery are low and recovery is quick."

Journal • CNS Disorders • Depression • Pain • Psychiatry

Zynrelef vs Exparel: The Battle of Postoperative Pain Control After Robotic Sleeve Gastrectomy (clinicaltrials.gov) - P1 | N=130 | Recruiting | Sponsor: Texas Tech University Health Sciences Center | Not yet recruiting ➔ Recruiting | Trial completion date: Apr 2025 ➔ Dec 2025 | Trial primary completion date: Apr 2025 ➔ Nov 2025

Enrollment open • Trial completion date • Trial primary completion date • Gastrointestinal Disorder • Pain

RCT of Extended-Release Bupivacaine/Meloxicam vs. Standard Periarticular Injection During Primary TKA (AAOS 2025) - "Controls received traditional intra-articular block (diluted ropivacaine, epinephrine, and ketorolac). This RCT determined that extended-release bupivacaine and meloxicam performed like our traditional ropivacaine-based periarticular injection when evaluating pain at 72 hours. There was a statistically, but not clinically, significant decrease in pain at 48 hours when accounting for opioid consumption in the extended-release bupivacaine and meloxicam group."

Immunology • Orthopedics • Osteoarthritis • Pain • Rheumatology

Phase 2B Upper Extremity Nerve Block Study (clinicaltrials.gov) - P2 | N=243 | Completed | Sponsor: Heron Therapeutics | Phase classification: P2b ➔ P2

Phase classification • Pain

Total Knee Arthroplasty Infiltration Study for Postoperative Analgesia (clinicaltrials.gov) - P2 | N=285 | Completed | Sponsor: Heron Therapeutics | Phase classification: P2b ➔ P2

Phase classification • Orthopedics • Pain

Heron Therapeutics Announces Fourth Quarter and Full-Year 2024 Financial Results and Highlights Recent Corporate Updates (PRNewswire) - "Generated ZYNRELEF Q4 2024 Net Revenue of $8.5 million and launched the ZYNRELEF Vial Access Needle ('VAN') in December 2024."

Sales • Pain

Drugs in Development to Manage Acute Pain. (PubMed, Drugs) - "These agents include VX-548 (Suzetrigine), Cebranopadol, AAT-076, Combogesic intravenous (IV), sublingual ketamine, XG004 (naproxen/pregabalin conjugate), and HTX-011 (Zynrelef). We analyze the pharmacodynamics, pharmacokinetics, development status, and clinical implications of these drugs, emphasizing the importance of finding an agent that provides both a strong safety profile and effective relief from acute pain. Our findings show promise but also highlight the need for further large-scale research to allow these drugs to be utilized in a clinical context for patients experiencing acute pain."

Journal • Review • Pain

Periarticular Bupivacaine + Meloxicam ER Solution Versus Standard Practice During Total Knee Arthroplasty (clinicaltrials.gov) - P4 | N=209 | Completed | Sponsor: Mayo Clinic | Enrolling by invitation ➔ Completed | N=98 ➔ 209

Enrollment change • Trial completion • Trial completion date • Trial primary completion date • Orthopedics • Pain

Nanotechnology for Pain Management. (PubMed, J Clin Med) - "This formulation is the base of DepoDur™, which comprises a combination of liposomes and extended-release morphine, and Exparel™, which comprises a combination of liposomes and extended-release bupivacaine...The use of liposome led to the development of DepoDur™, bupivacaine Exparel™ and a mixture of bupivacaine and meloxicam (Zynrelef™) and more recently lidocaine liposome formulation... Increasing evidence supports the concept that nanotechnology may represent a valuable tool as a drug transporter including liposomes and as a nanocapacitor-based device/patch to reduce or even eliminate the use of opioids in surgical patients. However, more studies are required to confirm this concept, especially with the use of nanotechnology incorporated in devices/patches."

Journal • Review • Addiction (Opioid and Alcohol) • Gastroenterology • Orthopedics • Pain

Zynrelef vs Exparel: The Battle of Postoperative Pain Control After Robotic Sleeve Gastrectomy (clinicaltrials.gov) - P1 | N=130 | Not yet recruiting | Sponsor: Texas Tech University Health Sciences Center | Initiation date: Apr 2024 ➔ Nov 2024

Trial initiation date • Gastrointestinal Disorder • Pain

Zynrelef vs Exparel: The Battle of Postoperative Pain Control After Robotic Sleeve Gastrectomy (clinicaltrials.gov) - P1 | N=130 | Not yet recruiting | Sponsor: Texas Tech University Health Sciences Center

New P1 trial • Gastrointestinal Disorder • Pain

Comparison of Systemic Extended-release Buprenorphine and Local Extended-release Bupivacaine-Meloxicam as Analgesics for Laparotomy in Mice. (PubMed, J Am Assoc Lab Anim Sci) - "None of the mice in thebupivacaine-meloxicam group developed signs of neurotoxicity, a potential side effect of high-dose local anesthetics. Thisstudy demonstrates that local ER bupivacaine-meloxicam may be a useful alternative to systemic, ER buprenorphine forthe relief of pain after laparotomy in mice."

Journal • Preclinical • Anesthesia • Pain

A Multi-surgery Assessment of ZYNRELEF (HTX-011), AMAZE. (clinicaltrials.gov) - P4 | N=30 | Completed | Sponsor: Heron Therapeutics

New P4 trial • Surgery • Musculoskeletal Pain • Orthopedics • Pain

A Multi-surgery Assessment of ZYNRELEF (HTX-011), AMAZE (clinicaltrials.gov) - P4 | N=30 | Completed | Sponsor: Heron Therapeutics

New P4 trial • Surgery • Aesthetic Medicine

A Multi-surgery Assessment of ZYNRELEF (HTX-011), AMAZE. Master Protocol HTX-011-401. (clinicaltrials.gov) - P4 | N=90 | Active, not recruiting | Sponsor: Heron Therapeutics | Recruiting ➔ Active, not recruiting | N=60 ➔ 90 | Trial completion date: Jun 2022 ➔ Jun 2024 | Trial primary completion date: Apr 2022 ➔ Jun 2024

Enrollment change • Enrollment closed • Surgery • Trial completion date • Trial primary completion date

Phase 2 Bunionectomy HTX-011 Administration Study (clinicaltrials.gov) - P2 | N=78 | Completed | Sponsor: Heron Therapeutics | N=60 ➔ 78

Enrollment change • Pain

HTX-011 in Spinal Surgery (clinicaltrials.gov) - P2 | N=32 | Completed | Sponsor: Heron Therapeutics | Recruiting ➔ Completed | N=94 ➔ 32 | Trial completion date: Dec 2022 ➔ Aug 2022 | Trial primary completion date: Nov 2022 ➔ Jul 2022

Enrollment change • Surgery • Trial completion • Trial completion date • Trial primary completion date • Pain

Pediatric Postoperative Analgesia Herniorrhaphy Study (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: Heron Therapeutics | N=336 ➔ 0 | Not yet recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal • Pediatrics

HeronBariatric: ZYNRELEF® for Postoperative Analgesia After Laparoscopic Sleeve Gastrectomy (clinicaltrials.gov) - P4 | N=120 | Recruiting | Sponsor: Dr. Yannis Raftopoulos

New P4 trial • Gastrointestinal Disorder • Pain

ZYNRELEF for Pain Management in Total Knee Arthroplasty (clinicaltrials.gov) - P4 | N=242 | Recruiting | Sponsor: Baptist Health South Florida | Not yet recruiting ➔ Recruiting

Enrollment open • Immunology • Orthopedics • Osteoarthritis • Pain • Rheumatology