Pacira's Gene Therapy PCRX-201 Shows Durable Two-Year Benefit in Knee Osteoarthritis, Phase 1 Data Published in Annals of the Rheumatic Diseases
核心洞察
A single intra-articular injection of PCRX-201 was well tolerated in patients with moderate-to-severe knee osteoarthritis (搜索) through two years of follow-up.
Exploratory outcome measures showed improvements in pain, stiffness, and function across all dose cohorts among patients who remained in the study.
Glucocorticoid pretreatment was associated with a lower rate of joint effusion and greater improvement in clinical outcomes, and has been incorporated into the ongoing Phase 2 ASCEND trial.
Pacira BioSciences (搜索) announced the publication of positive two-year results from its Phase 1 clinical trial of PCRX-201 (enekinragene inzadenovec), an investigational locally administered gene therapy for knee osteoarthritis (搜索), in the Annals of the Rheumatic Diseases. The study demonstrated that a single intra-articular injection of PCRX-201 into the knee was well tolerated in patients with moderate-to-severe knee osteoarthritis, with exploratory clinical outcome measures showing improvements in pain, stiffness, and function out to two years across all dose cohorts.
"Publication in Annals of the Rheumatic Diseases highlights the quality and importance of these findings," said Stanley Cohen, M.D., board-certified rheumatologist and Co-Medical Director of the Metroplex Clinical Research Center in Dallas, Texas, and lead investigator of the study. "The safety profile and the improvements observed across exploratory outcome measures over two years in this study provide a strong scientific rationale for the advancement of PCRX-201 into later-stage clinical development which is currently underway."
Study Design and Key Findings
The Phase 1 clinical trial was a two-part open-label study that enrolled 72 adults ranging in age from 30 to 80 years old with symptomatic, radiographically confirmed moderate-to-severe knee OA. In Part 1, 36 participants received a single injection of PCRX-201 at a low, middle, or high dose. In Part 2, 36 participants received methylprednisolone immediately before PCRX-201 administration to improve tolerability and evaluate whether glucocorticoid pretreatment could enhance vector transduction. The primary endpoint was safety; secondary and exploratory endpoints included systemic biodistribution and clinical outcomes measuring pain, stiffness, and function, with follow-up through 104 weeks.
Glucocorticoid pretreatment was associated with a lower rate of joint effusion and greater improvement in clinical outcomes, a finding that has been incorporated into the company's ongoing Phase 2 ASCEND study.
Regulatory Milestones and Platform Technology
PCRX-201 has received Regenerative Medicine Advanced Therapy (RMAT) designation from the U.S. Food and Drug Administration and Advanced Therapy Medicinal Products (ATMP) designation from the European Medicines Agency. It is the first gene therapy to achieve these clinical results and earn these regulatory designations in osteoarthritis of the knee.
The therapy is built on Pacira's proprietary high-capacity adenovirus (HCAd) vector platform, which the company states is more efficient at delivering genes into cells compared to AAV-based gene therapies, enabling smaller doses. The HCAd vector can carry up to 30,000 base pairs of DNA, allowing for gene therapy with multiple or larger genes. Additionally, therapies based on the platform can be administered locally and have the potential for redosing at appropriate therapeutic intervals.
Advancing to Phase 2
"Publication of these two-year Phase 1 data marks an important milestone for our gene therapy program and reinforces our belief in PCRX-201's potential to change the treatment landscape for knee osteoarthritis (搜索)," said Jonathan Slonin, MD, MBA, chief medical officer of Pacira BioSciences (搜索). "We are encouraged by the results observed to date, which, if confirmed in future studies, could meaningfully exceed the three-to-six-month duration of current therapies and deliver a treatment effect lasting one year or more, representing a potentially transformative advancement for patients."
The company recently announced that it has initiated enrollment in Part B of the Phase 2 ASCEND study (NCT06884865) and has implemented a successful transition of PCRX-201 to a scalable manufacturing process. The first topline readout from the ASCEND trial is on track for year-end 2026.
In June 2025, Pacira reported data from its ongoing clinical development program showing that PCRX-201 continues to demonstrate durable and clinically meaningful improvements in knee pain, stiffness, and function through three years following local administration, with a well-tolerated safety profile. Knee osteoarthritis (搜索) affects more than 15 million individuals in the U.S. today.