FRAXA backs upcoming Phase 2b trial of SPG601 for fragile X syndrome
Adaptive study will test oral BK-channel therapy in about 248 men with fragile X
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The FRAXA Research Foundation will provide financial support to the principal investigators involved in a planned Phase 2b clinical trial of SPG601, an experimental oral therapy being developed for people with fragile X syndrome.
“We are thrilled to have the support of FRAXA as part of our journey to develop a treatment for this rare and debilitating genetic disorder where there are currently no [U.S.-approved] treatments,” said Stella Sarraf, PhD, CEO and founder of Spinogenix, the therapy’s developer, in a company press release.
Phase 2a trial showed promising early signals
The continued evaluation of SPG601 builds on positive data from a completed Phase 2a clinical trial (NCT06413537). In that study of 10 men with fragile X, the therapy was reported to reduce abnormal brain activity and improve measures of attention.
The upcoming Phase 2b trial (NCT07439510) will test SPG601 in more than 200 men with fragile X. Its adaptive design could allow the study to transition directly into a Phase 3 trial if the results remain positive, potentially generating data needed to support an application for regulatory approval.
“After years of evaluating investigational therapies in FXS [fragile X syndrome], it is rare to see results this compelling and it is gratifying to see our collaboration with FRAXA continue as we advance SPG601,” said Craig Erickson, MD, Spinogenix’s chief medical advisor and principal investigator of the planned Phase 2b trial.
Fragile X syndrome is caused by mutations that disrupt the production of the FMRP protein, which plays an important role in normal brain development. As a result, people with fragile X may experience symptoms such as learning difficulties, anxiety, social avoidance, hyperactivity, and sensory sensitivities.
Specialized proteins known as BK channels help regulate the electrical activity of brain cells. In fragile X, these channels are thought to function abnormally, contributing to disrupted brain signaling.
SPG601 is designed to increase BK-channel activity, with the goal of improving communication between nerve cells and addressing brain signaling changes linked to fragile X.
SPG601 receives regulatory designations
SPG601 has received fast track designation in the U.S. and orphan drug status in both the U.S. and the European Union for fragile X syndrome. These regulatory designations are intended to speed the development and review of therapies for serious or rare conditions.
FRAXA has supported research into this treatment approach for several years.
“We have long believed that a mechanism targeting BK channels could make a significant difference to the lives of patients with FXS and their loved ones, and have consistently supported its development,” said Michael Tranfaglia, MD, co-founder of the FRAXA Research Foundation. “I was delighted to see our belief in SPG601 come to fruition with the Phase 2a trial providing the first evidence of efficacy in patients with FXS.”
The Phase 2a study evaluated a single dose of SPG601 in 10 men with fragile X, ages 18 to 45, using a placebo-controlled crossover design. After one week, participants switched treatments so that those who initially received placebo were given SPG601 and vice versa.
Top-line results indicated that SPG601 significantly reduced high-frequency gamma-band brain activity, measured using electroencephalography (EEG). Elevated gamma activity is commonly observed in fragile X and has been linked to cognitive difficulties. The therapy was also reported to improve measures of attention, including the ability to ignore distractions and maintain focus.
“The Phase 2a findings are among the most remarkable observed in FXS to date,” said Erickson, who also directs the Cincinnati Fragile X Research and Treatment Center. “The effects on gamma band activity, as seen in EEG recordings, along with correlated improvements in measures of attention and inhibitory control, highlight the promise of SPG601.”
Company plans adaptive Phase 2b/3 study
Following the Phase 2a results, Spinogenix met with the U.S. Food and Drug Administration (FDA) to discuss next steps in developing the therapy. The company and the agency aligned on the design of a planned Phase 2b/3 clinical trial that could serve as a registrational study — meaning its results may support a future application for regulatory approval if positive.
“We are thrilled to partner with the [principal investigators] working with Spinogenix to advance this BK channel opener in a larger registrational-directed study,” Tranfaglia said.
The Phase 2b/3 trial is designed to evaluate the safety, tolerability, and efficacy of SPG601. It is expected to enroll about 248 men with fragile X, ages 18-45. Participants must have a caregiver and be in generally good health with no significant medical conditions.
In its Phase 2b portion, participants will be randomly assigned to receive either one of several doses of SPG601 or a placebo, daily for four weeks. Researchers will evaluate changes in cognitive measures and brain-wave activity to help determine the most appropriate dose for later study stages.
Study could transition into Phase 3
If results from the Phase 2b portion are positive, the trial may proceed to its Phase 3 stage. In that part of the study, participants would be randomly assigned to receive either the selected dose of SPG601 or a placebo for about 12 weeks.
Researchers would evaluate similar outcomes as in Phase 2b, while also assessing additional validated measures of cognitive function, behavioral symptoms, and overall clinical status.
“My hope is that we are able to improve the quality of life of the patient and change their trajectory in life and this next trial allows us to get one step closer to that vision,” Sarraf said.
