Shionogi Update on Zatolmilast Fragile X Clinical Trial Findings
The long-awaited topline outcomes of Shionogi's clinical trials of zatolmilast have finally been announced, and unfortunately, they are not good.
Neither of the two Phase 3 clinical trials met the originally specified endpoint, cognitive improvement as measured by the NIH Toolbox. There was a glimmer of hope in that the adult trial showed a statistically significant improvement in the Numeric Rating Scale (NRS), a caregiver assessment of functioning that includes language use. However, the adolescent trial showed no such result. It is important to note that the NRS was a secondary outcome measure in the adult trial, so even though the improvement seen in adults was statistically significant compared to placebo, that result is not typically considered sufficient to obtain FDA approval for the drug.
We are pleased to hear that Shionogi plans to continue the open-label extension and to continue analyzing the data in hopes of conducting further trials. But this definitely sets the program back considerably. We continue to receive positive feedback from families participating in the trial; there is a general sense that this medication is effective, yet we continue to struggle to find the best clinical trial methods to demonstrate this.
We are profoundly disappointed by these findings. Every member of FRAXA’s staff and Board of Directors is a parent of one or more children with Fragile X, so we understand how painful and discouraging this is for families.
For many in our community, this is not the first trial setback. We are determined to learn as much as possible from this experience and to use those lessons to guide the next steps toward effective treatments and ultimately a cure for Fragile X syndrome.
FRAXA, the National Fragile X Foundation, and Shionogi hosted a community webinar on May 19, 2026, where Shionogi discussed this update and what comes next. We have included the recording for families who were unable to attend live or would like to revisit the conversation.
