Tetra Therapeutics, a wholly owned subsidiary of Shionogi & Co. Ltd., announced positive topline results from its Phase 2 exploratory study in adults diagnosed with Fragile X Syndrome (FXS). The study evaluated its lead candidate, BPN14770. In this single-center, randomized, placebo-controlled, two-way crossover study, BPN14770 demonstrated excellent safety as well as benefits on cognitive function and behavior in 30 adults with FXS.
BPN14770 is a novel therapeutic agent that selectively inhibits phosphodiesterase‐4D (PDE4D). In preclinical studies, BPN14770 promoted the maturation of connections between neurons, which is impaired in people with FXS, the most common genetic form of autism. The treatment has received Orphan Drug Designation from the U.S. Food and Drug Administration (FDA).
The Phase 2 clinical trial was a randomized, placebo-controlled, two-way crossover study conducted at Rush University Medical Center, Chicago, Illinois by principal investigator Elizabeth M. Berry-Kravis, M.D., Ph.D. with financial support from the FRAXA Research Foundation. The study featured two 12-week periods with no washout between periods. Between July 9, 2018 and July 31, 2020, the study enrolled 30 adult males with FXS who were between age 18 to 41 years. Each 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 results compared outcomes for the first period for those who received the placebo to those who received the active compound.
Cognitive assessments using the NIH-Toolbox revealed significant benefit in Oral Reading Recognition, Picture Vocabulary, and Cognition Crystallized Composite Score. Parent/Caregiver ratings using 100-point Visual Analog Scales revealed benefit that was judged to be clinically significant in Language and Daily Functioning. 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.
Tetra Therapeutics, a wholly owned subsidiary of Shionogi & Co., Ltd., is a clinical stage biotechnology company developing a portfolio of therapeutic products that will bring clarity of thought to people suffering from Fragile X syndrome, Alzheimer’s disease, traumatic brain injury, and other brain disorders. Tetra uses structure-guided drug design to discover mechanistically novel, allosteric inhibitors of the phosphodiesterase 4 (PDE4) enzymes, a family of enzymes that play key roles in memory formation, learning, neuroinflammation, and traumatic brain injury.
More information about the clinical trial is posted online at https://clinicaltrials.gov/ct2/show/NCT03569631 (accessed January 20, 2021).
This was reported by Tetra Therapeutics on November 2, 2020.