Evaluating Gene Therapy PCRX-201 for Osteoarthritis of the Knee

Derek Jackson, BS, MA

At the American Society of Gene & Cell Therapy (ASGCT) 28th Annual Meeting, held May 13 to 17, 2025, in New Orleans, LA, Mi Jeong Kim, PhD, the senior director of translational sciences at Pacira BioSciences, presented data from a phase 1 clinical trial evaluating enekinragene inzadenovec (PCRX-201), the company's investigational high-capacity adenovirus (HCAd) vector gene therapy intended to treat osteoarthritis (OA) of the knee through local administration. At the conference CGTLive® interviewed Derek Jackson, BS, MA, the vice president of cell & gene therapy product development at Pacira, to learn more.

Jackson explained the design of PCRX-201 and went over the key results that Kim presented. He also discussed future plans for the therapy and the potentially broad applications of the HCAd vector.

CGTLive: Can you give some background context about Pacira's PCRX-201 presentation at ASGCT?

Derek Jackson, BS, MA: My colleague Mi Jeong Kim, PhD, presented the findings from our phase 1 study of PCRX-201. PCRX-201 is a high capacity adenovirus and expresses human Interleukin-1 receptor antagonist with an inducible promoter. This was our 2-year data that included an analysis of our immune response and how baseline neutralizing antibodies to our vector impacted dosing. What we reported is that in our study, which was a large study for phase 1 (72 patients), 50% of the population had baseline neutralizing antibodies for adenovirus serotype 5, which is our capsid. In that study, we saw no impact of neutralizing antibody on efficacy or safety. This is encouraging for us because it does potentially pave the path for us exploring the ability to redose our therapy, which could be very meaningful for its market presentation.

How would you summarize the big picture implications you would want the broader healthcare community to take away from that?

We're developing PCRX-201 for osteoarthritis of the knee. It's a common disease. Fifteen million Americans have knee OA, and the numbers globally are significant, like in the hundreds of millions. So in this space, there's really been very little innovation in approved therapy. People are still using over the counter NSAIDs like Tylenol, injectable corticosteroids, and in some cases hyaluronic gel formulations for basically cushioning and lubrication of the joint.

The space has really been hungry for something that has greater impact, not only on pain and function, but also potentially on the ability to slow the progression of the disease. In the United States, for example, the age of osteoarthritis onset is getting younger, and eventually people move on to knee replacements. If we can help preserve the joint longer, that's going to have a meaningful impact in patients' lives and also a very positive impact on the healthcare system overall. So this program and the ability to potentially redose or to dose other joints once a patient has developed antibodies—those factors are really important to making a successful and usable therapy in this common disease.

Are there any future plans you can discuss?

So we've just started our ASCEND trial. It's a phase 2, double-blind, randomized, placebo-controlled study where all patients will receive a dose of corticosteroid at the beginning, including the placebo patients. This is really addressing the greatest development need for the program. The phase 1 study was an open-label study, and did not involve a placebo, as is common for a safety-only study, and also for a study where it was the first large clinical application of our particular vector, the high capacity adenovirus. So that study needed to be open-label so that we could monitor performance. We're very happy that the safety looked positive, and we did see signs of efficacy in that study. It was powered to probe patient-reported outcomes as an exploratory outcome. The next step is really just to take it into phase 2 and eventually define our final dose for phase 3. We've already narrowed the dose from 3 doses down to 2 doses for phase 2, so we expect to get out of this study our dosing regimen and the ultimate dose that we'll be using in phase 3.

This transcript has been edited for clarity.

Click here to view more coverage of the 2025 ASGCT Annual Meeting.

REFERENCE
1. Pacira Biosciences to present new data on clinical immunogenicity of intra-articular PCRX-201 and its implications for dosing strategy in knee osteoarthritis. News release. Pacira BioSciences, Inc. May 2, 2025. Accessed July 8, 2025. https://investor.pacira.com/news-releases/news-release-details/pacira-biosciences-present-new-data-clinical-immunogenicity