Zilretta (triamcinolone acetonide ER) / CSPC Pharma, Hong Kong Tainuo Pharma, Pacira - LARVOL DELTA

FormulationLAI: A physiology-based machine learning framework for accelerated development of long-acting injectable formulations. (PubMed, J Control Release) - "Using the commercial poly (lactic-co-glycolic acid) (PLGA)-based injectable Zilretta® as a benchmark, PBPK/PD modeling was used to define target in vitro release profiles that maximize therapeutic exposure...The transformative computational framework could significantly reduce the formulation development time during the preclinical phase from the traditional 5-7 years to approximately 1-2 years. This framework redefines the formulation paradigm: from empirical "formulate-and-test" to predictive "compute-and-validate", and offers a scalable strategy for rational, efficient development of long-acting injectables."

Journal

CoMeT: Corticosteroid Meniscectomy Randomized Trial (clinicaltrials.gov) - P4 | N=150 | Enrolling by invitation | Sponsor: The Cleveland Clinic | Trial primary completion date: Sep 2025 ➔ Jan 2026

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

ZILRETTA in Subjects With Shoulder Osteoarthritis (clinicaltrials.gov) - P3 | N=150 | Recruiting | Sponsor: Pacira Pharmaceuticals, Inc | N=250 ➔ 150 | Trial completion date: Aug 2025 ➔ Aug 2026 | Trial primary completion date: Aug 2025 ➔ Aug 2026

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

A Study to Evaluate an Intra-Articular Injection of ZILRETTA Versus Triamcinolone Acetonide, Immediate Release in Subjects With Osteoarthritis of the Hip (clinicaltrials.gov) - P2 | N=32 | Recruiting | Sponsor: Pacira Pharmaceuticals, Inc | Trial completion date: Dec 2025 ➔ Apr 2026 | Trial primary completion date: Dec 2025 ➔ Apr 2026

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

TKACSI: Use of Corticosteroid in Intraopertive Injections in Total Knee Replacement Surgery. (clinicaltrials.gov) - P2/3 | N=240 | Not yet recruiting | Sponsor: Walter Reed National Military Medical Center

New P2/3 trial • Immunology • Musculoskeletal Diseases • Orthopedics • Osteoarthritis • Pain • Rheumatology

Analgesic effect of local anesthesia in total knee arthroplasty: protocol of a randomized controlled clinical trial. (PubMed, Int J Surg Protoc) - "This phase II randomized controlled trial evaluates a dual-optimization strategy combining anatomic mapping-guided periarticular cutaneous nerve (PCN) blockade with a sustained-release triamcinolone-ropivacaine formulation to address these limitations. In this single-center, assessor-blinded, 2 × 2 factorial design, 120 adults undergoing primary unilateral TKA were randomized to four intervention arms: Group 1: Conventional iPACK (interspace between the popliteal artery and posterior knee capsule) site + novel formulation (1% ropivacaine + 40 mg triamcinolone); Group 2: PCN block site + standard formulation (1% ropivacaine + 5 mg dexamethasone); Group 3: PCN block + novel formulation; Group 4: Control (iPACK + standard formulation)...Primary endpoints included: resting/movement-induced pain intensity (Visual Analog Scale) at 6, 24, and 48 h postoperatively, cumulative opioid consumption (morphine milligram equivalents), functional recovery metrics (knee flexion..."

Clinical • Journal • Anesthesia • Infectious Disease • Orthopedics • Pain

CoMeT: Corticosteroid Meniscectomy Randomized Trial (clinicaltrials.gov) - P4 | N=150 | Enrolling by invitation | Sponsor: The Cleveland Clinic | Trial completion date: Aug 2025 ➔ Aug 2026 | Trial primary completion date: Jun 2025 ➔ Sep 2025

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

A Study to Evaluate an Intra-Articular Injection of ZILRETTA Versus Triamcinolone Acetonide, Immediate Release in Subjects With Osteoarthritis of the Hip (clinicaltrials.gov) - P2 | N=32 | Recruiting | Sponsor: Pacira Pharmaceuticals, Inc | Not yet recruiting ➔ Recruiting

Enrollment open • Immunology • Osteoarthritis • Pain • Rheumatology

Preparation and In Vitro Characterization of Triamcinolone Acetonide-Loaded Lipid Liquid Crystal Nanocarriers for Ocular Delivery. (PubMed, Adv Pharm Bull) - "This study aimed to develop sustained-release triamcinolone acetonide (TA) formulations using lipid liquid crystals (LLCs) for ocular drug delivery and to characterize the designed formulations. PLM analysis revealed the presence of hexosomes and cubosomes, indicating that an increase in hexosomes contributed to a more uniform drug release from the formulations. Overall, the study findings suggest that liquid crystalline carriers can be a promising formulation for sustained ocular drug delivery of TA."

Journal • Preclinical

Knee Osteoarthritis Treatment With Zilretta vs. Kenalog in the Context of Type II Diabetes (clinicaltrials.gov) - P4 | N=120 | Recruiting | Sponsor: University of Kansas Medical Center | Trial completion date: Jul 2026 ➔ Oct 2026

Trial completion date • Diabetes • Immunology • Metabolic Disorders • Osteoarthritis • Pain • Rheumatology • Type 2 Diabetes Mellitus

A Study to Evaluate an Intra-Articular Injection of ZILRETTA Versus Triamcinolone Acetonide, Immediate Release in Subjects With Osteoarthritis of the Hip (clinicaltrials.gov) - P2 | N=32 | Not yet recruiting | Sponsor: Pacira Pharmaceuticals, Inc

New P2 trial • Immunology • Osteoarthritis • Pain • Rheumatology

ZILRETTA™ for Treatment of Idiopathic Adhesive Capsulitis (clinicaltrials.gov) - P1 | N=39 | Terminated | Sponsor: University of Virginia | Recruiting ➔ Terminated; Not able to find enough subjects

Trial termination

CoMeT: Corticosteroid Meniscectomy Randomized Trial (clinicaltrials.gov) - P4 | N=150 | Enrolling by invitation | Sponsor: The Cleveland Clinic | Trial completion date: May 2025 ➔ Aug 2025 | Trial primary completion date: Mar 2025 ➔ Jun 2025

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

Treatment Journey for Nonoperative Symptomatic Knee Osteoarthritis: Data from a New Real-World Registry. (PubMed, Surg Technol Int) - "Patients who received IA-TAER were more likely to repeat the same injection, with 73% repeating at least once and no adverse events were attributed to repeated injections. Approximately half of the patients have switched from the initial treatment offered during follow up, with the use of IA-TAER associated with higher rates of repeated treatment. Significance and Innovation 1. Our study used a newly developed real-world registry IGOR to characterize treatment progression for patients with symptomatic knee OA undergoing up to five rounds of nonoperative treatment. 2. Non-surgical interventions included cryoneurolysis, intra-articular injections of NSAIDs, hyaluronic acid injections, corticosteroid, or extended release steroid (triamcinolone) injections. 3. We found 73% of patients treated with intra-articular extended-release steroid injections repeated treatment at least once, relative to 60% by other treatments. 4. We found approximately half of patients switched from..."

Journal • Real-world evidence • Immunology • Osteoarthritis • Pain • Rheumatology

Improved Sleep Associated With Triamcinolone Acetonide Extended-Release Injections for Knee Osteoarthritis: Use of a New Real-World Registry. (PubMed, Arthroplast Today) - "Extended-release triamcinolone injections are associated with decreased sleep disturbance relative to other treatments, in both degree of improvement and proportion of patients. Further studies should examine the potential beneficial effects of IA-TA-ER on other aspects of health-related quality of life."

Journal • Real-world evidence • CNS Disorders • Immunology • Osteoarthritis • Pain • Rheumatology • Sleep Disorder

Triamcinolone Acetonide Extended Release Injection does not Increase the Risk of PJI after Total Knee Arthroplasty (AAOS 2025) - "TA-ER injected within one year before TKA does not increase the risk of revision for PJI within one year following TKA. Furthermore, this risk profile is similar to HA and to a no-injection cohort, even when administered within 3 months of surgery."

Immunology • Infectious Disease • Orthopedics • Osteoarthritis • Pain • Rheumatology

Pacira BioSciences Reports Fourth Quarter and Full-Year 2024 Financial Results (Pacira Pharmaceuticals Press Release) - "In addition, the transaction is expected to provide near- and long-term financial benefits with the elimination of future milestone payments, including $4.5 million due at the initiation of a Phase 2 study of PCRX-201....EXPAREL net product sales were $147.7 million in the fourth quarter of 2024, a 3 percent increase over the $143.9 million reported for the fourth quarter of 2023; ZILRETTA net product sales were $33.1 million in the fourth quarter of 2024, a 15 percent increase over the $28.7 million reported for the fourth quarter of 2023."

Commercial • Sales • Immunology • Osteoarthritis • Pain

Use of Extended Release Triamcinolone in the Treatment of Rotator Cuff Disease (clinicaltrials.gov) - P3 | N=65 | Active, not recruiting | Sponsor: Northwell Health | Recruiting ➔ Active, not recruiting

Enrollment closed

Knee Osteoarthritis Treatment with Zilretta Vs. Kenalog in the Context of Type II Diabetes (clinicaltrials.gov) - P4 | N=120 | Recruiting | Sponsor: University of Kansas Medical Center | Not yet recruiting ➔ Recruiting

Enrollment open • Diabetes • Immunology • Metabolic Disorders • Osteoarthritis • Pain • Rheumatology • Type 2 Diabetes Mellitus

Pacira BioSciences Reports Second Quarter 2024 Financial Results (GlobeNewswire) - "ZILRETTA net product sales were $30.7 million in the second quarter of 2024, versus $29.3 million reported for the second quarter of 2023."

Sales • CNS Disorders • Immunology • Osteoarthritis • Pain

Improved Pain and Function with Triamcinolone Acetonide Extended-Release and Cryoneurolysis for Knee Osteoarthritis: Use of a New Real-World Registry. (PubMed, J Arthroplasty) - "The IA-TA-ER appears to outperform other treatments in terms of pain relief and functional improvement for up to 4 months following treatment. In addition, outcomes in the novel cryoneurolysis and conventional IA-CS were similar to one another and better than those in IA-HA and IA-NSAIDs."

Journal • Real-world • Real-world evidence • Immunology • Musculoskeletal Diseases • Musculoskeletal Pain • Orthopedics • Osteoarthritis • Pain • Rheumatology

Knee Osteoarthritis Treatment With Zilretta vs. Kenalog in the Context of Type II Diabetes (clinicaltrials.gov) - P4 | N=120 | Not yet recruiting | Sponsor: University of Kansas Medical Center

New P4 trial • Diabetes • Immunology • Metabolic Disorders • Osteoarthritis • Pain • Rheumatology • Type 2 Diabetes Mellitus

Extended-Release Versus Immediate-Release Triamcinolone Acetonide in Patients Who Have Knee Osteoarthritis and Type 2 Diabetes Mellitus. (PubMed, J Arthroplasty) - "Use of TA-ER was associated with a clinically meaningful reduction in hyperglycemia versus TA-IR."

Journal • Diabetes • Immunology • Metabolic Disorders • Osteoarthritis • Pain • Rheumatology • Type 2 Diabetes Mellitus

Pacira BioSciences Reports First Quarter 2024 Financial Results and Announces $150 Million Share Repurchase program (GlobeNewswire) - P1 | N=72 | NCT04119687 | Sponsor: Pacira Pharmaceuticals, Inc | "Net product sales of $132.4 million for...for ZILRETTA...investigators presented encouraging preliminary results from a 72-patient study of PCRX-201 data at the Osteoarthritis Research Society International, or OARSI, 2024 World Congress in Vienna, Austria....The data showed that a single intra-articular injection of PCRX-201 demonstrated sustained clinical effect as assessed by patient-reported outcomes at all dose levels for at least one-year post-injection. Importantly, PCRX-201 was shown to be well-tolerated with a favorable safety profile. The company expects to submit updated data demonstrating PCRX-201’s effectiveness through two years for presentation at a medical meeting in the Fall."

P1 data • Sales • CNS Disorders • Osteoarthritis • Pain

Effect of PLGA raw materials on in vitro and in vivo performance of drug-loaded microspheres. (PubMed, Drug Deliv Transl Res) - "Lupron Depot® and Zilretta® were used as reference commercial products. In summary, this work details information on comparing the similarities and differences in in vitro and in vivo performance of drug-loaded microspheres as a function of manufacturing and microstructural variables of different types of PLGA raw materials utilized and could, therefore, be meaningful in guiding the source control during development and manufacturing of PLGA microsphere-based drug products. Future work will expand the analysis to include a broader range of LL and higher Rc, and add additional important formulation metrics (e.g., thermal analysis, and residual monomer, moisture, and organic solvent levels)."

Journal • Preclinical • Inflammatory Arthritis