FDA clears Phase 2 trial of oral SPG601 in men with fragile X

Patient dosing to start this year, Spinogenix says

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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The U.S. Food and Drug Administration (FDA) has given Spinogenix the green light for a Phase 2 clinical trial that will test its investigational oral therapy SPG601 in adult men with fragile X syndrome.

“Current treatments leave a critical gap in effective and patient-friendly solutions for neurodevelopmental conditions,” Stella Sarraf, PhD, founder and CEO of Spinogenix, said in a company press release, and the therapy address an “unmet need” in fragile X syndrome. “The expansion of clinical programs with SPG601 represents an important step in our progress to bringing innovative treatments that offer new hope, and we look forward to dosing the first patient in the trial this year,” Sarraf said.

Fragile X is a neurodevelopmental disease characterized by a range of neurological symptoms including intellectual disability, language delays, motor problems, behavioral issues, and seizures, among others.

There’s currently no FDA-approved therapy specifically for the rare condition, “despite the considerable impact of FXS,” said Craig Erickson, MD, Spinogenix’s chief medical advisor. Disease management largely relies largely on interventions to ease symptoms and improve life quality.

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Targeting BK channels

Fragile X is caused by mutations in the FMR1 gene, leading to low to no levels of FMRP, a protein involved in the normal development and maturation of synapses in the brain. A synapse is the site of near contact between nerve cells where they release chemical signals to communicate with each other, which is critical for proper brain function.

Many proteins involved in synapse formation are dysregulated and synapses don’t mature properly in fragile X patients, contributing to the profound neurological symptoms that characterize the disease.

According to Spinogenix, many core fragile X symptoms have been associated with low activity of large conductance, calcium-activated potassium channels, or BK channels. These brain-abundant channels are involved in synapse function.

“BK channel function has been shown to be abnormal in many animal studies in the Fragile X field,” Erickson said.

SPG601 is a small molecule designed to bind to and activate BK channels. Administered as a once-daily pill, the therapy is expected to help restore synaptic function and ease core symptoms in fragile X patients.

The Phase 2a trial will compare the neurophysiological and clinical effects of single-dose SPG601 against a placebo, according to the company.

“We look forward to the first study of a BK channel modulator in humans with Fragile X and taking the first step to evaluate this important drug mechanism in Fragile X Syndrome,” Erickson said.

The company is developing another therapy candidate, SPG302, for other neurological conditions marked by synapse loss, including amyotrophic lateral sclerosis, Alzheimer’s disease, and schizophrenia.