Spinogenix, Inc. has announced positive topline results from its Phase 2 clinical trial of SPG601, a novel therapeutic for Fragile X syndrome (FXS). The study, conducted in adult men with FXS, met its primary endpoint by demonstrating a significant reduction in high-frequency gamma band activity, an electroencephalogram (EEG) abnormality characteristic of FXS that impairs brain activity crucial for learning and memory.
The randomized, double-blind, placebo-controlled, crossover study involved ten adult male patients with core attributes of FXS. Participants received a single dose of SPG601 or a matching placebo. The trial's success marks a significant step forward in addressing the unmet medical need for FXS, a leading inherited cause of intellectual disability and a known cause of autism.
Mechanism of Action and Clinical Significance
SPG601 is a small molecule designed to enhance synaptic function by targeting large-conductance, calcium-activated potassium (BK) channels. By increasing the activation of these channels, SPG601 aims to correct specific synaptic dysfunctions underlying many core symptoms of FXS, such as anxiety, social aversion, hyperactivity, and sensory hypersensitivity. Currently, there are no FDA-approved treatments specifically targeting the underlying synaptic deficits in FXS.
Dr. Craig Erickson, Spinogenix Chief Medical Advisor and principal investigator of the Phase 2 study at Cincinnati Children's Hospital Medical Center, stated, "This is the strongest test result to date demonstrating a therapy normalizing gamma band activity, which is directly associated with learning, memory, and typical brain activity."
Regulatory Status and Future Development
SPG601 has been granted Fast Track designation by the U.S. Food and Drug Administration (FDA), which will expedite its development and regulatory review. The FDA had previously granted Orphan Drug designation to SPG601 for the treatment of FXS in May 2024. These designations underscore the urgent need for new therapies to address this debilitating condition.
Dr. Stella Sarraf, Spinogenix Chief Executive Officer and Founder, commented, "This is an exciting milestone for SPG601 at a time when there are no approved treatments for FXS. We are focused on developing SPG601 as a first-in-class treatment for FXS capable of restoring synapse function."
Fragile X Syndrome: An Unmet Need
FXS affects approximately 1 in 4,000 to 5,000 men and 1 in 6,000 to 8,000 women worldwide. The condition results from the silencing of the Fmr1 gene and leads to a spectrum of disabling symptoms, including intellectual disability, anxiety, social aversion, and seizures. The annual direct healthcare costs for families affected by FXS in the United States alone amount to $4.1 billion.
Spinogenix is also developing SPG302 for treating amyotrophic lateral sclerosis (ALS).
