Efficacy and Safety of FX201, a Novel Intra-Articular IL-1Ra Gene Therapy for Osteoarthritis Treatment, in a Rat Model

Hum Gene Ther. 2022 May;33(9-10):541-549. doi: 10.1089/hum.2021.131. Epub 2022 Mar 18.


Osteoarthritis (OA) is a disabling, degenerative disease characterized by progressive cartilage and bone damage. There remains a need for local therapies that, following a single injection, can provide long-term pain relief and functional improvement and potentially delay disease progression. FX201 is a novel, intra-articular (IA), interleukin-1 receptor antagonist (IL-1Ra) gene therapy in development for the treatment of OA. In this study, we assessed the efficacy, biodistribution, and safety of helper-dependent adenovirus (HDAd)-ratIL-1Ra, the rat surrogate of FX201, and the biodistribution of FX201, in the anterior cruciate ligament transection (ACLT) rat OA model. A single IA injection of HDAd-ratIL-1Ra administered 7 days post-ACLT mitigated OA-related changes to cartilage, bone, and the synovial membrane at week 12 following surgery. Furthermore, FX201 and HDAd-ratIL-1Ra persisted for at least 92 days in the injected joint and proximal tissues with minimal evidence of vector spreading peripherally. Finally, HDAd-ratIL-1Ra showed a favorable safety profile without any local or systemic adverse effects. In conclusion, HDAd-ratIL-1Ra demonstrated local therapeutic and disease-modifying effects and was well tolerated, supporting further clinical development of FX201.

Keywords: FX201; disease models > muscle/connective tissue/bone; disease modification; gene therapy; immunogenicity; osteoarthritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Animals
  • Disease Models, Animal
  • Genetic Therapy
  • Injections, Intra-Articular
  • Interleukin 1 Receptor Antagonist Protein* / genetics
  • Osteoarthritis* / genetics
  • Osteoarthritis* / metabolism
  • Osteoarthritis* / therapy
  • Rats
  • Synovial Membrane / metabolism
  • Tissue Distribution


  • Interleukin 1 Receptor Antagonist Protein