Tetra Therapeutics, a wholly owned subsidiary of Shionogi & Co. Ltd., announced positive topline results from its Phase 2 exploratory study evaluating BPN14770 in adult patients with Fragile X Syndrome (FXS). BPN14770 demonstrated excellent safety as well as benefits on cognitive function and behavior.
This was a randomized, placebo-controlled, two-way crossover study, with each period of 12 weeks in duration with no washout between periods. The study enrolled 30 adult male subjects age 18-41 years with FXS due to >200 CGG repeats in the FMR1 gene. Subjects received daily oral doses of 25 mg twice a day of BPN14770 or placebo. Parents/caregivers and physician raters were blinded to treatment. All subjects completed both treatment periods, although carryover effects limited the primary statistical analysis to Period 1. The following results, therefore, describe the outcomes for patients who received BPN14770 during Period 1, compared to those who received placebo.
Cognitive assessments using the NIH-Toolbox revealed significant benefit in Oral Reading Recognition (LSMean Difference +2.80), Picture Vocabulary (+5.79), and Cognition Crystallized Composite Score (+5.29). Parent/Caregiver ratings using 100 point Visual Analog Scales revealed benefit that was judged to be clinically significant in Language (LSMean Difference +14.04) and Daily Functioning (+14.53). The benefit of BPN14770 was maintained up to 12 weeks after the crossover from drug to placebo. BPN14770 was very well tolerated in the Phase 2 trial with few adverse events.
BPN14770 selectively inhibits phosphodiesterase-4D (PDE4D) to increase the levels of cAMP, a key signaling molecule, in brain. In preclinical models, BPN14770 promotes the maturation of connections between neurons, which is impaired in patients with Fragile X Syndrome. This unique mechanism of action has the potential to improve cognitive and memory function in CNS disorders, including FXS, Alzheimer’s disease and other dementias, learning/developmental disabilities and schizophrenia.
BPN14770 received Orphan Drug Designation from the U.S. Food and Drug Administration (FDA) for Fragile X Syndrome.
About Fragile X Syndrome
Fragile X syndrome (FXS) is a genetic disorder. FXS is caused by changes in a gene that scientists called the fragile X mental retardation 1 (FMR1) gene when it was first discovered. The FMR1 gene usually makes a protein called fragile X mental retardation protein (FMRP). FMRP is needed for normal brain development. People who have FXS do not make this protein. People who have other fragile X-associated disorders have changes in their FMR1 gene but usually make some of the protein.
FXS affects both males and females. However, females often have milder symptoms than males. The exact number of people who have FXS is unknown, but a review of research studies estimated that about 1 in 7,000 males about 1 in 11,000 females have been diagnosed with FXS.