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

Novel Extended-Release Bupivacaine Polymer for Sustained Pain Relief Following Total Knee Arthroplasty (clinicaltrials.gov) - P4 | N=150 | Recruiting | Sponsor: Henry Ford Health System

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

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 | Trial completion date: Dec 2025 ➔ Dec 2028 | Trial primary completion date: Nov 2025 ➔ Nov 2027

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

Post-Operative Pain Relief: Zynrelef or Periarticular Injections in RATKA (clinicaltrials.gov) - P4 | N=150 | Not yet recruiting | Sponsor: Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute) | Initiation date: Jan 2026 ➔ Jul 2026

Trial initiation date • Immunology • Musculoskeletal Pain • Orthopedics • Osteoarthritis • Pain • Rheumatology

Zynrelef Versus Adductor Canal Block (clinicaltrials.gov) - P4 | N=120 | Not yet recruiting | Sponsor: University of Miami | Initiation date: Jun 2026 ➔ Jan 2027

Trial initiation date • Immunology • Orthopedics • Osteoarthritis • Pain • Rheumatology

Study of Post-Herniorrhaphy Non-opioid MMA Regimens (clinicaltrials.gov) - P3 | N=209 | Completed | Sponsor: Heron Therapeutics | Phase classification: P3b ➔ P3 | N=115 ➔ 209

Enrollment change • Phase classification • Pain

ZYNRELEF for Pain Management in Total Knee Arthroplasty (clinicaltrials.gov) - P4 | N=29 | Terminated | Sponsor: Baptist Health South Florida | N=242 ➔ 29 | Trial completion date: Dec 2027 ➔ Dec 2025 | Recruiting ➔ Terminated | Trial primary completion date: Oct 2027 ➔ Dec 2025; Study discontinued due to feasibility challenges related to participant recruitment

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Immunology • Orthopedics • Osteoarthritis • Pain • Rheumatology

Triple-layered core-shell microneedle patch for sustained analgesic delivery and chondroprotection in osteoarthritis. (PubMed, J Control Release) - "Subsequently, the system provides a controlled, co-delivery of Bupivacaine (BUP) and Meloxicam (MEL), which act synergistically to provide sustained anesthetic and anti-inflammatory effects for up to 10 days (for comparison, the only commercial long-acting Zynrelef™ drug for post-operational pain only has up to 3-day acting period) in OA rat models. Besides the analgesic efficacy, the MIRACLE system demonstrated a significant capacity to mitigate articular cartilage degradation. This multi-layered MNs platform could represent an excellent strategy for not only the treatment of chronic osteoarthritis pain but also the management of other types of neuromusculoskeletal pains, offering a significant and broad impact on modern medicine."

Journal • Anesthesia • Immunology • Musculoskeletal Diseases • Musculoskeletal Pain • Osteoarthritis • Pain • Rheumatology

Total Knee Arthroplasty (TKA) Study of HTX-011 in an Multimodal Analgesic Regimen (MMA) Regimen (clinicaltrials.gov) - P3 | N=116 | Completed | Sponsor: Heron Therapeutics | Phase classification: P3b ➔ P3

Phase classification • Orthopedics • Pain

Post-Operative Pain Relief: Zynrelef or Periarticular Injections in RATKA (clinicaltrials.gov) - P4 | N=150 | Not yet recruiting | Sponsor: Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)

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

ZYNRELEF vs Continuous Catheter for Pain Management Following Shoulder Arthroplasty (clinicaltrials.gov) - P4 | N=86 | Enrolling by invitation | Sponsor: Washington University School of Medicine | Not yet recruiting ➔ Enrolling by invitation

Enrollment open • Orthopedics • Pain

Zynrelef Versus Adductor Canal Block (clinicaltrials.gov) - P4 | N=120 | Not yet recruiting | Sponsor: University of Miami | Initiation date: Jan 2026 ➔ Jun 2026

Trial initiation date • Immunology • Orthopedics • Osteoarthritis • Pain • Rheumatology

Use of Zynrelef (bupivacaine and meloxicam) to eliminate the need for opioids in laparoscopic pre-peritoneal inguinal hernia repairs. (PubMed, Surg Endosc) - "Results of this study display adequate pain management following TEP procedures with the use of Zynrelef and a reduction in the use of opioids compared to patients undergoing TEP without Zynrelef. The findings from this study are in alignment with findings from other studies such as the HOPE trial in which Zynrelef was used in patients with open inguinal hernias and displayed an opioid-free rate of 91%."

Journal • Addiction (Opioid and Alcohol) • Anesthesia • Gastroenterology • Pain

ZYNRELEF vs Continuous Catheter for Pain Management Following Shoulder Arthroplasty (clinicaltrials.gov) - P4 | N=86 | Not yet recruiting | Sponsor: Washington University School of Medicine

New P4 trial • Orthopedics • Pain

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