Pacira BioSciences has initiated the Phase 2 ASCEND clinical trial for PCRX-201 (enekinragene inzadenovec), dosing the first patient in a study that could potentially transform treatment options for knee osteoarthritis. The novel gene therapy is designed to address the underlying inflammatory processes that contribute to joint degeneration in osteoarthritis, a condition affecting more than 14 million Americans.
PCRX-201 represents a significant advancement in the treatment landscape for knee osteoarthritis, where current therapies typically provide only three to six months of relief. The therapy is administered locally into the knee joint and works by boosting the production of interleukin-1 receptor antagonist (IL-1Ra), which blocks the interleukin-1 pathway activation associated with chronic inflammation, pain, and reduced function.
"We are excited to advance PCRX-201 into Phase 2 clinical development as it marks an important milestone on our 5x30 path to growth and value creation, as well as our transition into an innovative biopharmaceutical organization," said Frank D. Lee, chief executive officer of Pacira. "There is a significant need for innovation in the treatment of OA of the knee, as current therapies are based on decades-old mechanisms and only provide up to three to six months of relief."
Study Design and Endpoints
The ASCEND study is structured as a two-part, multicenter trial involving approximately 135 patients aged 45 to 80 years with painful knee osteoarthritis. Participants will have Kellgren-Lawrence (K-L) Grades of 2, 3, or 4, representing moderate to severe disease.
The trial will evaluate two doses of PCRX-201:
- Dose A: 1.4 x 10^10 genome copies (GC)
- Dose B: 1.4 x 10^11 GC
Patients will be randomized in a 1:1:1 ratio to receive either Dose A, Dose B, or saline. All treatment groups will receive concurrent pretreatment with an intraarticular corticosteroid (methylprednisolone 40 mg), a common technique in gene therapy dosing to improve tolerability and gene transfer.
Part A of the study will randomize approximately 45 patients, while Part B will include about 90 patients. The drug product used in Part B will be manufactured using Pacira's newly developed suspension-based batch manufacturing process intended for commercial scale-up.
The primary endpoint focuses on safety, measuring the number and percentage of treatment-emergent adverse events, adverse events of special interest, and serious adverse events through Week 52. Secondary and exploratory endpoints include efficacy assessments such as changes in pain and physical function from baseline at Weeks 38 and 52, measured using validated instruments including the Numerical Rating Scale (NRS), the Western Ontario and McMaster Universities Index (WOMAC), and the Knee Injury and Osteoarthritis Outcome Score (KOOS).
Promising Phase 1 Results
The advancement to Phase 2 follows encouraging results from a large Phase 1 study reported in November 2024, where PCRX-201 demonstrated sustained improvements in knee pain, stiffness, and function through two years following local administration, with a well-tolerated safety profile.
"In our large Phase 1 study, a single intra-articular injection of PCRX-201 was well tolerated and demonstrated unprecedented pain relief and durability across all levels of OA severity for at least two years," Lee noted. "PCRX-201 has the potential to address the underlying chronic inflammatory processes that contribute to OA joint degeneration over time, with local administration that is contained in the joint – delivering medicine where it matters."
Innovative Technology Platform
PCRX-201 is built on Pacira's proprietary high-capacity adenovirus (HCAd) vector gene therapy platform, which the company acquired in February 2025 with the purchase of GQ Bio Therapeutics. This platform addresses several challenges that have limited gene therapy applications in common diseases like osteoarthritis.
The HCAd vector technology offers several advantages:
- Greater efficiency in delivering genes into cells compared to adenovirus associated virus (AAV) vectors
- Capacity to carry up to 30,000 base pairs of DNA, enabling therapy with multiple or larger genes
- Potential for local administration and redosing at therapeutically appropriate intervals
- Efficient production capabilities, with thousands of doses possible in a single batch
A unique feature of PCRX-201 is its inducible promoter, which mimics the body's natural response to inflammation by activating IL-1Ra expression when inflammation is present in the joint and deactivating when inflammation subsides.
Regulatory Support and Timeline
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. These designations are intended to expedite development and review processes for promising therapies targeting significant unmet needs.
According to Pacira, PCRX-201 is the first gene therapy to achieve these clinical results and earn these regulatory designations in osteoarthritis of the knee, highlighting its potential to address a major treatment gap.
Pacira expects to report topline results from Part A of the ASCEND study before the end of 2026. All study participants will be followed for a total of 5 years to assess long-term outcomes.
Expanding the Non-Opioid Pain Management Portfolio
The development of PCRX-201 aligns with Pacira's broader mission to deliver innovative, non-opioid pain therapies. The company currently markets three commercial-stage non-opioid treatments: EXPAREL® (bupivacaine liposome injectable suspension), ZILRETTA® (triamcinolone acetonide extended-release injectable suspension), and iovera°, a device for delivering drug-free pain control using controlled cold temperature.
If successful, PCRX-201 would represent a significant addition to this portfolio, potentially offering a durable, disease-modifying approach to a condition that currently lacks long-term effective treatments.
