enekinragene inzadenovec (PCRX-201) / GQ Bio Therap, Pacira - LARVOL DELTA

PCRX-201 High-Capacity Adenovirus Serotype 5 Gene Therapy Demonstrates Sustained Clinical Efficacy and Safety in Patients With Knee Osteoarthritis (ACR Convergence 2025) - P1 | "A single IA injection of PCRX-201 with corticosteroid pretreatment in patients with knee OA had an acceptable safety profile and sustained clinical efficacy for up to 156 weeks. Preexisting NAbs did not affect PCRX-201 efficacy or safety at all 3 doses, and corticosteroid pretreatment demonstrated greater improvement in the clinical scores than no pretreatment. These results support the ongoing phase 2 study strategy of PCRX-201 with a 10-fold lower dose (1.4E11 GC) and steroid pretreatment."

Clinical • Gene therapy • Gene Therapies • Immunology • Inflammation • Osteoarthritis • Pain • Rheumatology

A Study to Assess Safety and Tolerability of PCRX-201 in Subjects With Painful Osteoarthritis of the Knee (clinicaltrials.gov) - P2 | N=135 | Recruiting | Sponsor: Pacira Pharmaceuticals, Inc | Trial primary completion date: Aug 2028 ➔ Mar 2027

Trial primary completion date • Immunology • Osteoarthritis • Pain • Rheumatology • CXCL8

A Single Intra-articular Injection of the Gene Therapy PCRX-201 Was Safe and Provided Sustained Clinical Benefits for Patients With Moderate-to-Severe Knee Osteoarthritis Through 3 Years (EULAR 2025) - P1 | "A single IA injection of PCRX-201 in the index knee had an acceptable safety profile with improvements in pain, function, and stiffness sustained through 156 weeks, indicating long-term clinical efficacy. The sustained improvements in WOMAC pain and stiffness scores at 156 weeks suggest that lower doses of PCRX-201 may be sufficient to provide efficacy in future clinical studies. Study follow-up is ongoing through 260 weeks."

Clinical • Gene therapy • Gene Therapies • Immune Modulation • Immunology • Osteoarthritis • Pain • Rheumatology

Pacira BioSciences Unveils Three-Year Clinical Data Following a Single Local Administration of Investigational Gene Therapy, PCRX-201, in Patients with Moderate-to-Severe Osteoarthritis of the Knee (GlobeNewswire) - P1 | N=72 | NCT04119687 | Sponsor: acira Pharmaceuticals, Inc | "A single injection of PCRX-201 at any dose level had an acceptable safety profile and was not associated with any serious treatment-related adverse events. Patients experienced sustained, clinically meaningful reductions in pain and stiffness and improvements in function for three years. Least squares mean (LSM) improvements from baseline in the corticosteroid-pretreated cohort across all PCRX-201 doses included: 51–53% reduction in WOMAC-A pain scores; 38–76% reduction in WOMAC-B stiffness scores; 26–28-point improvements in KOOS daily living function scores;

P1 data • Immunology • Osteoarthritis

Understanding the Clinical Immunogenicity of Locally Injected HCAd Vector Provides Insight Into Optimizing Dosing Strategy (ASGCT 2025) - P1 | "Preexisting NAb did not affect PCRX-201 efficacy or safety at all 3 doses, and steroids helped to reduce induced NAb titers and dose-related AE incidence. These results support the planned phase 2 study strategy of PCRX-201 with 10-fold lower dose (1.4E11 GC), steroid pretreatment, and potential for PCRX-201 redosing in future trials. Disease Focus of Abstract:Arthritis"

Clinical • Gene Therapies • Immunology • Inflammation • Osteoarthritis • Pain • Rheumatology

Pacira BioSciences to Present New Data on Clinical Immunogenicity of Intra-Articular PCRX-201 and Its Implications for Dosing Strategy in Knee Osteoarthritis (GlobeNewswire) - "Pacira BioSciences, Inc...announced an upcoming podium presentation of findings from its Phase 1 study of PCRX-201 (enekinragene inzadenovec), a locally administered gene therapy candidate for osteoarthritis of the knee. The data will be presented at the 28th Annual Meeting of the American Society of Gene and Cell Therapy (ASGCT) in New Orleans on May 15. The presentation will highlight how preexisting and treatment-induced neutralizing antibodies (NAbs) impact the therapy’s efficacy, safety, and redosing potential."

P1 data • Osteoarthritis

Pacira BioSciences Announces Two-Year Efficacy Data Following a Single Local Administration of PCRX-201 in Patients with Mild to Severe Osteoarthritis of the Knee (GlobeNewswire) - P1 | N=72 | NCT04119687 | Sponsor: Pacira Pharmaceuticals, Inc | "Pacira BioSciences, Inc...today announced new data demonstrating its locally administered gene therapy candidate, PCRX-201 (enekinragene inzadenovec), provided sustained improvements in knee pain, stiffness, and function for up to two years following a single local administration in patients with mild, moderate, as well as severe osteoarthritis of the knee. The data was presented during a poster session at the 2025 Osteoarthritis Research Society International (OARSI) World Congress in Incheon, South Korea, on Friday, April 25, and Saturday, April 26."

P1 data • Osteoarthritis

Pacira BioSciences to Present 104-Week Efficacy Data Following a Single Local Administration of PCRX-201 for Patients with Mild to Severe Osteoarthritis of the Knee (GlobeNewswire) - "Pacira BioSciences, Inc...today announced the upcoming presentation of new 104-week data in support of its locally administered gene therapy candidate, PCRX-201 (enekinragene inzadenovec). The data is being presented at the 2025 Osteoarthritis Research Society International (OARSI) World Congress in Incheon, South Korea, April 24-27."

Clinical data • Osteoarthritis

Pacira BioSciences Announces First Patient Dosed in Phase 2 Study Evaluating Safety and Efficacy of PCRX-201 for the Treatment of Osteoarthritis of the Knee (GlobeNewswire) - "Pacira BioSciences, Inc...today announced the first patient has been dosed in the Phase 2 ASCEND study of PCRX-201 (enekinragene inzadenovec) for the treatment of osteoarthritis, or OA, of the knee....Pacira expects to report topline results from Part A of the study before the end of 2026."

P2 data • Trial status • Osteoarthritis

A Study to Assess Safety and Tolerability of PCRX-201 in Subjects With Painful Osteoarthritis of the Knee (clinicaltrials.gov) - P2 | N=135 | Recruiting | Sponsor: Pacira Pharmaceuticals, Inc

New P2 trial • Immunology • 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

Sustained Clinical Effects After a Single Intra-articular Injection of PCRX-201 for Moderate-to-Severe Osteoarthritis of the Knee (ACR Convergence 2024) - P1 | "A single IA injection of PCRX-201 in the index knee had an acceptable safety profile with improvements in pain across K/L grades to 104 weeks, indicating sustained clinical efficacy. From these data, future studies will employ steroid pretreatment. These results support further investigation of PCRX-201 in OAK in randomized, double-blind, active-controlled studies planned for 2025."

Clinical • Immune Modulation • Immunology • Inflammation • Osteoarthritis • Pain • Rheumatology

PCRX-201, a novel IL-1Ra gene therapy treatment approach for low back pain resulting from intervertebral disc degeneration. (PubMed, Gene Ther) - "This demonstrates PCRX-201 enables the inhibition of IL-1-driven IVD degeneration. The ability of PCRX-201 to elicit anti-catabolic responses is promising and warrants further development to determine the efficacy of this exciting, novel gene therapy."

Gene therapy • Journal • Back Pain • Gene Therapies • Lumbar Back Pain • Musculoskeletal Pain • Pain • ACAN • IL1B • IL1R1 • IL6 • MMP3

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

Sustained Clinical Effects of Single-Dose Intraarticular PCRX201 Injection in Moderate-to-Severe Osteoarthritis of the Knee (ASGCT 2024) - P1 | "Collectively, these data suggest the IA PCRX201 has an acceptable safety profile and provides sustained clinical effects at all dose levels up to 52 weeks postinjection as measured by validated patient-reported outcome assessments. These promising preliminary results warrant further investigation of PCRX201 in an ongoing randomized controlled Phase 1b trial."

Clinical • Immunology • Osteoarthritis • Pain • Rheumatology • IL1B

Pacira BioSciences Announces PCRX-201 Granted Regenerative Medicine Advance Therapy (RMAT) Designation for the Treatment of Osteoarthritis of the Knee (GlobeNewswire) - "Pacira BioSciences, Inc...announced that the U.S. Food and Drug Administration (FDA) has granted Regenerative Medicine Advanced Therapy (RMAT) designation to PCRX-201 (enekinragene inzadenovec), the company’s novel, intra-articular helper-dependent adenovirus (HDAd) gene therapy product candidate that codes for interleukin-1 receptor antagonist (IL-1Ra), for the treatment of osteoarthritis of the knee....'we continue to be encouraged by the preliminary clinical findings supporting PCRX-201 as a potential disease-modifying therapy for osteoarthritis, and we look forward to presenting additional follow-up data later this year'."

FDA event • P1 data • Immunology • Osteoarthritis • Rheumatology

Safety and Preliminary Efficacy of PCRX201, an Intra-Articular Gene Therapy for Knee Osteoarthritis: A Phase 1, Open-Label, Single Ascending Dose Study (ASGCT 2023) - P1 | "Most index knee AEs were treated with rest, ice, acetaminophen, and synovial fluid aspiration. PCRX201 was generally well-tolerated, with a decreased severity and incidence of index knee events in the steroid-pretreated cohort versus the nonpretreated cohort. Preliminary efficacy results suggested considerable pain improvement across all doses."

Clinical • Gene therapy • P1 data • Gene Therapies • Immunology • Osteoarthritis • Pain • Rheumatology

SAFETY AND PRELIMINARY EFFICACY OF PCRX201,AN INTRA-ARTICULAR GENE THERAPY FOR KNEEOSTEOARTHRITIS: A PHASE 1, OPEN-LABEL, SINGLEASCENDING DOSE STUDY (OARSI 2023) - No abstract available

Clinical • Gene therapy • P1 data • Gene Therapies • Immunology • Osteoarthritis • Pain • Rheumatology

Safety And Preliminary Efficacy Of Pcrx201, An Intra-Articular Gene Therapy For Knee Osteoarthritis: A Phase 1, Open-Label, Single Ascending Dose Study (OARSI 2023) - "PCRX201 is a helper-dependent adenovirus that expresses the IL-1 receptor antagonist (IL-1Ra) gene triggered by a nuclear factor-kappa B (NF-kB) responsive promoter; in vivo transduction enables local IL-1Ra gene expression in the presence of inflammation. Herein, we report preliminary results from a phase 1 study that assessed the safety and efficacy of PCRX201 in knee OA."

Clinical • Gene therapy • P1 data • Gene Therapies • Immunology • Inflammation • Osteoarthritis • Pain • Rheumatology • NFKB1 • NF-κβ

Study to Evaluate the Safety and Tolerability of FX201 in Patients With Osteoarthritis of the Knee (clinicaltrials.gov) - P1 | N=72 | Active, not recruiting | Sponsor: Flexion Therapeutics, Inc. | Trial primary completion date: Nov 2022 ➔ Nov 2023

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

Study to Evaluate the Safety and Tolerability of FX201 in Patients With Osteoarthritis of the Knee (clinicaltrials.gov) - P1 | N=72 | Active, not recruiting | Sponsor: Flexion Therapeutics, Inc. | Trial completion date: Nov 2023 ➔ Nov 2026

Trial completion date • Immunology • Osteoarthritis • Pain • Rheumatology

Efficacy and Safety of FX201, a Novel Intra-Articular IL-1Ra Gene Therapy for Osteoarthritis Treatment, in a Rat Model. (PubMed, Hum Gene Ther) - "Finally, HDAd-ratIL-1Ra showed a favorable safety profile without any local or systemic adverse effects. In conclusion, HDAd-ratIL-1Ra demonstrated local therapeutic and disease-modifying effects and was well tolerated, supporting further clinical development of FX201."

Journal • Preclinical • Gene Therapies • Immunology • Osteoarthritis • Pain • Rheumatology • IL1R1

Study to Evaluate the Safety and Tolerability of FX201 in Patients With Osteoarthritis of the Knee (clinicaltrials.gov) - P1; N=72; Active, not recruiting; Sponsor: Flexion Therapeutics, Inc.; Recruiting ➔ Active, not recruiting; N=105 ➔ 72

Clinical • Enrollment change • Enrollment closed • Immunology • Osteoarthritis • Pain • Rheumatology

[VIRTUAL] A firstinhuman, phase 1, openlabel trial of FX201, an intraarticular, helperdependent adenoviral gene therapy for osteoarthritis preliminary evaluation of clinical activity in 8 patients from the middose cohort of a single ascending dose study design (ESGCT 2021) - P1 | "Three Grade 2 adverse index knee events managed conservatively and one Grade 3 adverse event treated successfully with an intraarticular steroid injection were observed. 7 of 8 patients showed reduction in pain (WOMACA) and functional improvement (KOOSADL) at 24 weeks following administration of middose FX201, 4 of whom showed substantial improvement by IMMPACT criteria for Weeks 824."

Clinical • P1 data • Gene Therapies • Immunology • Osteoarthritis • Pain • Rheumatology

Study to Evaluate the Safety and Tolerability of FX201 in Patients With Osteoarthritis of the Knee (clinicaltrials.gov) - P1; N=105; Recruiting; Sponsor: Flexion Therapeutics, Inc.; N=66 ➔ 105

Clinical • Enrollment change • Immunology • Osteoarthritis • Pain • Rheumatology