Pacira has completed enrollment in Part A of its Phase 2 ASCEND trial of PCRX-201, a locally administered IL‑1Ra gene therapy for knee osteoarthritis. The 45‑patient, three‑arm cohort tests two intra‑articular dose levels—1.4 × 10^10 GC and 1.4 × 10^11 GC—against saline, with all groups receiving a 40 mg intra‑articular methylprednisolone pretreatment. The primary endpoint is safety through Week 52; secondary endpoints include pain and functional changes at Weeks 38 and 52, assessed using NRS, WOMAC, and KOOS. Topline Part A readout is targeted for late 2026.
The study is structured as a two‑part, multicenter Phase 2 enrolling approximately 135 patients aged 45–80 with K‑L Grade 2–4 disease. Part A informs dose selection and CMC readiness for Part B, which will randomize ~90 patients using a drug product manufactured with Pacira’s commercial‑scale process. All participants will be followed for five years, with biomarker, immunogenicity, biodistribution, and structural measures incorporated to address gene therapy expectations in a prevalent, non‑rare indication. The program holds RMAT and ATMP designations. Pacira has previously reported multi‑year signals of durable symptom improvement in earlier studies, but quantitative efficacy for this randomized Phase 2 study remains to be established.
Operationally, Pacira is pushing a hybrid objective: de‑risking dose and safety while front‑loading manufacturing scale‑up. Tying Part B to the commercial process aims to compress the CMC pathway typical of gene therapies —an approach aligned with RMAT engagement but that raises the execution bar for tech transfer and lot consistency sooner. The HCAd vector architecture and inducible promoter are positioned to address two challenging problems in OA gene therapy—redosing feasibility and inflammation‑tuned expression—yet the methylprednisolone pretreatment across all arms could dampen early inflammatory signals and blur efficacy separation at interim time points. With safety as the primary endpoint, Part A is primarily a dose‑finding and platform-proofing exercise rather than an efficacy inflection.
For sites, this is a procedural gene-therapy study conducted in an orthopedic/rheumatology setting, with gene‑therapy oversight requirements: vector handling SOPs, biosafety governance, and long‑horizon follow‑up. The five‑year tail, immunogenicity sampling, potential biodistribution assessments, and structural evaluations will test retention and data completeness—particularly in community sites that do not routinely run gene therapy protocols. CROs will need to bridge orthopedic networks with gene therapy quality systems, manage temperature‑controlled investigational product and clinic‑based injections, and ensure rigorous PRO capture at Weeks 38 and 52, where efficacy is assessed. For sponsors and payers watching from the sidelines, the choice of control arm matters: saline plus steroid avoids a head‑to‑head comparison with standard intra‑articular therapies. That simplifies Part A but postpones the comparator conversation that will be central to payer evidence and guideline adoption.
Regulatory dynamics favor early and frequent dialogue. RMAT can facilitate agreement on clinically meaningful endpoints in OA, where function and pain must be paired with safety and, ideally, structural signals to support disease modification claims. The immunogenicity profile—neutralizing antibodies, redosing feasibility, and vector shedding—will be pivotal, as will any indication that local expression modulates downstream cartilage structure rather than just symptoms. Manufacturing credibility will come under equal scrutiny; claims of favorable cost‑of‑goods for a high‑volume OA market need to withstand commercial‑scale batch analytics and yield data.
Next to watch: which dose advances to Part B and the rationale driving it, the timing of Part B initiation relative to the Part A readout, evidence of separation on WOMAC/KOOS at one year despite universal steroid pretreatment, and early CMC signals from the commercial‑scale process. Strategic tension remains around portfolio cannibalization, given Pacira’s ownership of Zilretta and the pace at which the program moves toward an active‑comparator design acceptable to regulators and payers. The gating risks are immunogenicity that limits redosing, variability in site execution across a five‑year follow‑up, and CMC scale‑up complexity that could erode the timeline advantage Pacira is trying to build.
Jon Napitupulu is Director of Media Relations at The Clinical Trial Vanguard. Jon, a computer data scientist, focuses on the latest clinical trial industry news and trends.
