Study shows significant cognitive improvement in domains related to language and caregivers reported improved language and daily functioning
Lead drug candidate continues to be safe and well-tolerated
Grand Rapids, MI, November 2, 2020 (Business Wire) – Tetra Therapeutics, a wholly owned subsidiary of Shionogi & Co. Ltd., today announced positive topline results from its Phase 2 exploratory study in adult patients with Fragile X Syndrome (FXS). The study evaluated its lead candidate, BPN14770, a first-in-class phosphodiesterase‐4D (PDE4D) allosteric inhibitor. 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 patients 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 patients with FXS, the most common genetic form of Autism.
“We are very excited about the results of this study,” said Mark Gurney PhD, Founder and Chief Executive Officer of Tetra. “In addition to being safe and well-tolerated, treatment with BPN14770 led to significant cognitive improvement, specifically in the language domains, and we also saw a clinically meaningful benefit in overall daily functioning. These findings validate our approach to treating this disease through a mechanism that addresses a core deficit in the disorder. On behalf of the entire Tetra team, I want to sincerely thank the patients, families and investigators who participated in this study as well as the FRAXA Research Foundation, for their assistance in this study.”
The Phase 2 clinical trial was a randomized, placebo-controlled, two-way crossover study. Each period was 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. Study enrollment occurred between July 9, 2018 and July 31, 2020. 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, p=0.0157), Picture Vocabulary (+5.79, p=0.0342), and Cognition Crystallized Composite Score (+5.29, p=0.0018). Parent/Caregiver ratings using 100 point Visual Analog Scales revealed benefit that was judged to be clinically significant in Language (LSMean Difference +14.04, p=0.0051) and Daily Functioning (+14.53, p=0.0017). 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.
“These results offer hope for Fragile X Syndrome patients and their parents” said Dr. Elizabeth Berry-Kravis, pediatric neurologist, Rush University Medical Center, and principal investigator. “The preponderance of clinical outcome measures were in favor of the drug. These included performance-based as well as parent and physician-rated scales which suggests a meaningful impact on the global FXS disease process. I find it exciting that we have a drug that potentially addresses 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.”
Mark Gurney, PhD MBA
2220 Wealthy Street SE
Grand Rapids, MI 49506