Recruitment Opens for Men with Fragile X Syndrome in Phase 3 Trial of BPN14770

Investigational treatment will be evaluated on ability to improve cognition

Patricia Inácio, PhD avatar

by Patricia Inácio, PhD |

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Tetra Therapeutics has announced the opening of its first site for a Phase 3 clinical trial assessing the safety and effectiveness of BPN14770 (zatolmilast), its investigational oral therapy for fragile X syndrome.

The Suburban Research Associates, a clinical site in Pennsylvania, is now recruiting male adult patients, ages 18-45. Patients wishing to join can apply online. For further information, email Meghan Verano at [email protected].

One of three pivotal Phase 2b/3 studies recently launched by Tetra, the trial (NCT05358886) will randomly assign 150 men to a placebo or BPN14770. A second trial (NCT05163808), with the same design, will recruit male adolescents, ages 12-17. Recruitment is underway at Rush University Medical Center, Chicago, and Cincinnati Children’s Hospital Medical Center, Ohio.

“We are excited to initiate these pivotal trials with BPN 14770 in patients with Fragile X syndrome, and are hopeful that the results of these studies will enable us to seek approval from FDA,” Chad Coberly, Tetra’s CEO, said in a FRAXA Research Foundation’s press release.

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The main goal in both studies is to evaluate BPN14770’s effectiveness in improving cognition after 13 weeks (around three months), as assessed using a set of cognitive tests developed at the National Institutes of Health (NHI). These are called NIH-Toolbox Cognitive Battery (NIH-Toolbox). Additional goals include assessing the therapy’s safety and tolerability, as well as the therapy’s pharmacokinetics, or its movement into, through, and out of the body.

Patients who complete one of the two trials can join an open-label extension study (NCT05367960) where all participants will be treated with BPN14770. The studies will be conducted over two years.

Elizabeth Berry-Kravis, MD, PhD, pediatric neurologist at Rush University Medical Center, is the trial’s lead investigator.

“We are anxious to get started with these studies that offer hope for people living with Fragile X syndrome and their caregivers,” Berry-Kravis said.

BPN14770 was designed to selectively bind and partially suppress the activity of an enzyme called phosphodiesterase 4D (PDE4D). PDE4D helps regulate a brain-signaling molecule called cyclic adenosine monophosphate (cAMP). Involved in learning and memory formation, the levels of cAMP are reduced in fragile X patients. By boosting them, BPN14770 may help promote nerve cell connections and improve cognitive function in fragile X patients.

Data from preclinical animal studies and a previous Phase 2 trial showed the investigational therapy led to marked improvements in cognition, particularly in language, and daily functioning in men with fragile X.

If the new trials support these initial positive findings, Tetra plans to seek approval for BPN14770 with the U.S. Food and Drug Administration (FDA).

“Given our previous positive results with BPN14770 in the phase 2 study, we are hopeful these studies at a larger scale will show similar results. I find it exciting that we have a drug that potentially corrects a core deficit in FXS, a decrease in cAMP, that has been documented in patients as well as in the fly and mouse models of the disorder,” said Berry-Kravis.

The therapy has previously received orphan drug designation by the FDA as a treatment for fragile X.