SPG601 calms brain activity in men with fragile X, helping them to focus
Trial data show therapy helps people filter out irrelevant information
Spinogenix’s experimental oral therapy SPG601 reduced abnormal high-frequency brain activity in men with fragile X syndrome and increased their selective attention, allowing them to better focus on one type of information while ignoring others.
That’s according to full data from a Phase 2a clinical trial (NCT06413537) completed early this year. The trial tested a single SPG601 dose against a placebo in 10 men with fragile x, ages 18 to 45, over roughly two weeks.
“With no current approved treatment and an urgent global need for effective options, SPG601 has the potential to represent an important step forward in FXS [fragile X syndrome] treatment development,” Craig Erickson, MD, Spinogenix’s chief medical advisor and the trial’s principal investigator, said in a company press release.
Erickson, who also leads the Cincinnati Fragile X Research and Treatment Center, is presenting the complete Phase 2a findings at the American Academy of Child & Adolescent Psychiatry (AACAP) conference, taking place Oct. 20-25 in Chicago.
FDA guidance provides path for Phase 2b/3 trial
Building on the encouraging Phase 2a results, Spinogenix had a type C meeting with the U.S. Food and Drug Administration (FDA) to receive guidance on the therapy’s development.
During that meeting, the company and FDA agreed on the design of a future Phase 2b/3 trial, a potential registrational study. Registration studies are trials whose data, if positive, can support filings for regulatory approval of a therapy.
“We are excited to continue demonstrating SPG601’s potential as a first-in-class treatment for [fragile X syndrome],” said Stella Sarraf, PhD, CEO and founder of Spinogenix. “These trial results together with the recent positive Type C meeting with the FDA provide a clear path forward for the development of SPG601.”
Fragile X syndrome is caused by mutations in the FMR1 gene, which provides instructions for producing a protein called FMRP. This protein helps in the proper development of synapses, or the sites of near-contact between nerve cells where electrical signals are relayed for communication.
A loss or shortage of the FMRP protein disrupts normal communication between nerve cells in the brain. As a result, nerve cells fire electrical signals more readily than usual, which can lead to sensory overload and hyperactive behavior.
SPG601 is designed to restore normal communication between nerve cells. It increases how long big potassium (BK) channels stay open. BK channels control excitability by allowing potassium to exit nerve cells. When potassium flows outward, nerve cells return to their resting state, which is thought to ease symptoms in fragile X patients.
SPG601 has received fast track designation in the U.S. and orphan drug designation in both the U.S. and the European Union for treating fragile X syndrome. These special statuses are designed to accelerate the therapy’s clinical development and regulatory review.
Tracking SPG601’s impact on brain activity
In the Phase 2a trial, men with a genetically confirmed fragile X diagnosis were randomly assigned to receive a single dose of SPG601 — 800 mg delivered as eight oral capsules — or a placebo. One week later, the groups switched, and those initially assigned the placebo received SPG601, and vice versa.
One of the trial’s main goals was to measure changes in high-frequency gamma band activity in the brain. This activity is typically elevated in people with fragile X and linked to difficulties with learning and memory. The changes were assessed with an electroencephalogram (EEG), which records the brain’s electrical activity.
Consistent with earlier top-line results, EEG data showed SPG601 was significantly superior to the placebo at reducing this “neurophysiological biomarker of FXS,” the release stated, suggesting trends toward normalized brain activity.
Researchers also monitored changes in overall symptoms, responses to stimuli, attention, memory, and cognitive function. They found SPG601 improved selective attention, or the ability to ignore distractions and focus, which is often reduced in people with fragile X syndrome.
At the conference, Erickson will also receive the AACAP George Tarjan, MD, Award, recognizing his contributions to the understanding of developmental disabilities, including fragile X research that has helped guide SPG601’s development.
“I am honored by the recognition from the AACAP and its members,” Erickson said. “The successful implementation of objective neurophysiological outcomes in the clinical testing of SPG601 represents a significant milestone in the development of novel therapeutics for FXS and gratifying application of work I have pursued throughout my career.”
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