PCRX-201 (enekinragene inzadenovec)
Pacira is redefining innovation in gene therapy to bring its benefits to the population at large, starting with osteoarthritis of the knee (OAK). PCRX-201 is currently being studied in the fundamental, underlying chronic inflammatory processes that contribute to “wear and tear” over time in OAK.
This page displays a pipeline drug candidate currently undergoing clinical testing. The safety and efficacy of this drug candidate have not been fully evaluated by any regulatory authority, including the U.S. Food and Drug Administration, for any indication.
Osteoarthritis of the knee
A serious disease starved for innovation
OAK is a highly prevalent, degenerative, and painful condition affecting approximately 14 million people in the United States alone. Patients aren’t satisfied with current treatment options, which only provide 3-6 months of relief and are based on decades-old mechanisms that don’t address the drivers of disease.1-3
This lack of innovation has created apathy, leading patients to believe they need to accept their pain and the impact it has on their life. Millions of patients per year are receiving total knee replacements as a last resort, which are expensive, can have complications, and aren’t guaranteed solutions.
PCRX-201: Redefining gene therapy innovation to bring its benefits to the population at large
PCRX-201’s innovative design, manufacturing process, and local administration aims to solve many of the challenges that have made gene therapy inaccessible for common diseases.
PCRX-201 is designed to be injected locally into the knee joint to boost cellular IL-1Ra production and block IL-1 pathway activation, intended to reduce chronic inflammation.
PCRX-201’s innovative HCAD vector is designed to be an efficient vector to deliver genes, which potentially means less medication to achieve the desired effect.
PCRX-201 is designed to use an inflammation-responsive promoter intended to only produce IL-1Ra when needed, mimicking the body’s natural response to inflammation.
The IL-1 pathway: A root cause of disease
It’s been known for years that chronic IL-1 activation is an underlying driver of knee inflammation, joint degeneration, and pain. Several FDA-approved drugs have successfully targeted the IL-1 pathway in other joint inflammatory conditions, proving that blocking its activation is a well-validated, de-risked strategy for reducing inflammation. However, these existing drugs aren’t practical for OAK because they would require very high doses or daily injections into the knee.
A potential revolution in OAK treatment
PCRX-201 is designed to supplement receptor antagonist (IL-1Ra) production, which blocks IL-1 pathway activation and dampens down chronic inflammation in the knee.
PCRX-201 is poised to transform how we approach osteoarthritis treatment, helping patients get back to normal and stay there for years rather than months.
PCRX-201 has already shown promise in early-stage clinical trials
PCRX-201 is currently being evaluated in a robust Phase 1 trial with 72 OAK patients (NCT04119687).
In this study, PCRX-201 has shown promise for delivering exceptional, long-lasting pain relief and durability for patients across all levels of disease severity (KL2-KL4), with benefits lasting at least two years from a single injection. The majority of patients (>70%) experienced a >50% improvement in pain and stiffness. Given that most other therapies provide relief for only 3-6 months, PCRX-201 has the potential to set a new standard for sustained pain relief.
No serious treatment-emergent AEs related to the treatment or procedure were reported regardless of steroid pretreatment or dose level administered. Treatment-related joint effusions (swelling) were the most common AE, occurring in 36% of patients who received steroid pretreatment vs 61% of patients who were not pretreated. The majority of effusions were mild to moderate in severity and resolved in a median of 33 days among patients in the pretreated group.
PCRX-201 is the first gene therapy to achieve these results and is the only OA gene therapy to earn the FDA Regenerative Medicine Advanced Therapy (RMAT) designation.
*Data from steroid pretreated cohort
References
- Osteoarthritis Research Society International White Paper Osteoarthritis: A Serious Disease, Submitted to the U.S. Food and Drug Administration Dec. 1, 2016.
- A National Public Health Agenda for Osteoarthritis: 2020 Update; Osteoarthritis Action Alliance (Centers for Disease Control and Arthritis Foundation).
- Voice of the Patient; Osteoarthritis Foundation Summary Report from FDA’s Patient-Focused Drug Development Meeting Sep. 30, 2017.