Sangamo Therapeutics has announced that the U.S. Food and Drug Administration (FDA) has cleared the Investigational New Drug (IND) application for ST-503, a novel gene therapy targeting chronic neuropathic pain associated with idiopathic small fiber neuropathy (iSFN). The company plans to initiate a Phase 1/2 clinical trial in mid-2025 to assess the safety, tolerability, and preliminary efficacy of this innovative treatment. This clearance marks a significant step forward in addressing a condition with limited long-lasting or curative therapies.
Targeting Chronic Neuropathic Pain
ST-503 is designed as a one-time intrathecal treatment that utilizes an adeno-associated virus (AAV) vector to deliver a zinc finger repressor (ZFR) directly to the SCN9A gene. This gene encodes the Nav1.7 sodium channel, a key mediator of pain signaling. By selectively silencing the SCN9A gene, ST-503 aims to reduce the expression of Nav1.7 sodium channels in sensory neurons, thereby alleviating pain hypersensitivity.
Nathalie Dubois-Stringfellow, Ph.D, Chief Development Officer at Sangamo, stated, "The FDA’s clearance of the IND application to evaluate ST-503 in idiopathic small fiber neuropathy represents an important milestone for Sangamo on our journey to becoming a neurology genomic medicine company."
Clinical Trial Design and Patient Population
The Phase 1/2 clinical study will evaluate the safety and efficacy of ST-503 in patients with intractable pain due to iSFN. This peripheral neuropathy results in debilitating symptoms such as burning, prickling, stabbing, or "lightning-like" pain. The trial will administer a one-time dose of ST-503 intrathecally. Sangamo anticipates initiating patient enrollment in mid-2025.
Preclinical Evidence
Preclinical research has demonstrated that ST-503 is well-tolerated in nonhuman primates, with substantial Nav1.7 reduction observed and no off-target effects. These findings suggest that ST-503 holds promise as a potential therapy for chronic neuropathic pain, regardless of the underlying cause.
Unmet Medical Need in Neuropathic Pain
Neuropathic pain can arise from various pathologies affecting the central or peripheral nervous systems, including surgical trauma, spinal cord injury, nerve compression, neurological and infectious diseases, or metabolic and hereditary syndromes. iSFN affects an estimated 43,000 patients in the U.S., while broader peripheral neuropathies impact nearly 40 million Americans. Current treatment options, such as antidepressants, anticonvulsants, opioids, and topical therapies, often fail to provide long-lasting relief, highlighting the urgent need for more effective therapies.
Sangamo believes that if the Phase 1/2 study is successful, the development of ST-503 could be expanded to include patient populations suffering from other types of chronic neuropathic pain.
