Genascence Corporation announced positive six-month interim safety and biomarker results from its Phase 1b DONATELLO clinical trial evaluating GNSC-001, an investigational AAV gene therapy for knee osteoarthritis (OA). The data indicate that GNSC-001, which encodes interleukin 1 receptor antagonist (IL-1Ra), was safe and well-tolerated across multiple dosing arms.
The six-month analysis demonstrated that GNSC-001 achieved acceptable safety and tolerability across all doses tested, along with encouraging biomarker data. Mean IL-1Ra expression reached and maintained target levels in synovial fluid throughout the six-month follow-up period. The study also found that immune-conditioning with a short steroid course supported higher levels of transgene expression.
Clinical Significance
"These six-month interim results mark a critical milestone in our mission to transform the treatment paradigm for osteoarthritis," said Jeymi Tambiah, M.D., chief medical officer of Genascence. "The safety profile and sustained IL-1Ra expression data underscore the promise of GNSC-001 as a potential one-time gene therapy for this debilitating condition. The results from DONATELLO will guide discussions with regulatory authorities as Genascence prepares to initiate a Phase 2 trial focused on clinical efficacy."
Targeting IL-1 in Osteoarthritis
Annahita Keravala, Ph.D., chief scientific officer of Genascence, highlighted the significance of these findings: "The ability to locally and sustainably inhibit IL-1 activity in the joint has been a long-standing goal in osteoarthritis research. GNSC-001 is the first IL-1 inhibitor that has been shown to generate IL-1Ra expression levels that reach and maintain therapeutic thresholds in the synovial fluid long-term following a single administration. This highlights the potential of our gene therapy approach to address a key mediator of inflammation and disease progression in osteoarthritis and offers hope for a transformative treatment option for patients."
