Intraarticular Gene Therapy Well-Tolerated, Improves Pain in Knee Osteoarthritis


Updated data from a phase 1 study of PCXR201, formerly known as Flexion’s FX201, were presented at the 2023 ASCGT Annual Meeting.

PCXR201 (Pacira Biosciences), a gene therapy being investigated for the treatment of knee osteoarthritis (OA), was generally well-tolerated and yielded improvements in knee pain in treated participants in a phase 1 study (NCT04119687).

Updated data from the study were presented at the 2023 American Society of Gene and Cell Therapy (ASGCT) Annual Meeting, taking place May 16-20 in Los Angeles, California, by Stanley B. Cohen, MD, clinical professor, Department of Internal Medicine, University of Texas Southwestern Medical School.

“PCRX201 is a novel, helper-dependent adenovirus that locally expresses IL1RN and is designed to be activated be a nuclear factor κB-responsive promoter during inflammation to reflect a natural response. The IL1RN completely blocks binding of both IL-1α and IL-1β but has no inherent signaling capabilities itself,” Cohen and colleagues wrote in their poster.

The trial enrolled 72 participants to receive 1 of 3 dose levels across 2 cohorts. In the 36 participants in the not-pretreated cohort, 12 received low dose (2.8E9 GC/mL), 16 received middle dose (2.8E10 GC/mL), and 8 received high dose (2.8E11 GC/mL) PCRX201. These participants had a median age of 62.0 years (interquartile range [IQR], 58.5-67.0). In the 36 participants in the steroid pretreated cohort, 13 received low dose, 15 received middle dose, and 8 received high dose PCRX201. These participants had a median age of 67.5 years (IQR, 58.5-71.5).

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Median follow-up was 64.9 weeks (range, 15.1-106.1) in the non-pretreated cohort and 37.6 weeks (range, 7.6-52.0) in the steroid pretreated cohort. As of the data cutoff date, 13 participants (36%) in the not-pretreated cohort and 11 (31%) in the steroid pretreated cohort had discontinued from the study.

The trial is primarily assessing safety via adverse events (AEs), with a secondary efficacy endpoint of change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Investigators found that the main treatment-related AE (TRAE) was index knee effusion, which generally resolved with conservative care or intraarticular steroids. There were no severe TRAEs and index knee effusions were less severe and frequent (13 vs 25) in the steroid pretreated cohort compared to the not-pretreated cohort. Other TRAEs, including chills and headache, were similar between cohorts.

Investigators observed improvements in knee pain on WOMAC across all dose groups in both cohorts, with 60% of participants in both cohorts reaching over a 50% reduction from baseline in WOMAC scores at week 20. From a sample set in the not-pretreated cohort, investigators found that systemic baseline neutralizing antibodies didn’t appear to affect TRAEs or WOMAC scores.

“Preliminary results from this phase 1, open-label trial are promising and support further investigation of PCRX201 for knee OA. This study is ongoing and participants will be followed for 5 years,” Cohen and colleagues wrote.

Cohen S, Kivitz A, Klassen L, et al. Safety and preliminary efficacy of PCRX201, an intraarticular gene therapy for knee osteoarthritis: A phase 1, open-label, single ascending dose study. Presented at: 2023 ASGCT Annual Meeting; May 16-20; Los Angeles, California. Poster #1376
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