Genascence’s first-in-class gene therapy blocking interleukin 1, GNSC-001, will enter a Phase IIb/III study in 2026.
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Clinical-stage biotechnology company Genascence Corporation announced on July 16, 2025, that its potential first-in-class gene therapy blocking interleukin 1 (IL-1) for the treatment of knee osteoarthritis (OA) was granted Regenerative Medicine Advanced Therapy (RMAT) designation by FDA. The agency also granted the therapy Fast Track designation in 2024.
The gene therapy, GNSC-001, is a “recombinant adeno-associated viral vector expressing an optimized human interleukin-1 receptor antagonist (IL-1Ra), a naturally occurring protein that blocks IL-1 signaling” (1). A key mediator in the pathogenesis of OA, IL-1 causes inflammation, joint pain, and damage to cartilage, according to Genascence. The new gene therapy was designed to provide long-term, sustained inhibition of IL-1 after a single intra-articular injection in an affected joint.
The initiation of a Phase IIb/III study, designed in coordination with FDA, is expected for 2026 (1). A single-center, open-label, dose-escalation design Phase I first-in-human study included nine patients with knee OA. A Phase Ib clinical trial, DONATELLO, was a double-blind, placebo-controlled dose-ranging study that evaluated the safety, tolerability, and pharmacodynamics of a single intra-articular injection. DONATELLO included 67 participants at 10 centers in the United States and was supported by a $12 million award from the California Institute for Regenerative Medicine (CLIN2-14265).
RMAT designation, which is granted to drug candidates that show the potential to treat, modify, reverse, or cure life-threatening diseases or those conditions with an unmet need, can speed up development and review of cell and gene therapies as defined in the 21st Century Cures Act (2). The designation provides sponsor companies with the benefits of fast-track and breakthrough therapy, accelerated development and review pathways, and the potential for accelerated approval.
“GNSC-001 is the first IL-1 inhibitor for OA that has been shown to generate IL-1Ra expression levels that maintain therapeutic thresholds long-term following a single administration to inhibit pathogenic IL-1,” said Thomas Chalberg, PhD, founder and CEO of Genascence, in a press release (1). “The FDA RMAT designation for GNSC-001 underscores the strength of the clinical data to date, recognizing its potential to transform the treatment paradigm for OA. With the RMAT designation for GNSC-001, we look forward to working closely with the FDA as we seek to accelerate late-stage clinical development of GNSC-001 so we can bring a new treatment option to people suffering from this incapacitating, disabling disease.”
OA is a progressive joint disease that causes pain and loss of function, potentially leading to disability. It impacts more than 30 million Americans and represents an economic burden due to medical costs and a lack of productivity (1). While often treated with currently available pain medications, such as steroids and opioids, there is no currently available therapy to slow disease progression.
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