Treatment with a first-in-class phosphodiesterase‐4D (PDE4D) allosteric inhibitor (BPN14770; Tetra to adults with Fragile X Syndrome (FXS; n=30) in a phase 2 exploratory study (NCT03569631). In this single-center randomized placebo-controlled 2-way crossover study, the PDE4D inhibitor lasted up to 12 weeks after switching from treatment to placebo.
Those who received 25 mg of the PDE4D twice a day had improved oral reading recognition (mean difference +2.81, P=.0157), picture vocabulary (+5.81, P=.0342), and the cognition crystallized composite score (+5.31, P=.0018). Parent/caregiver ratings using 100 point visual analog scales revealed clinically meaningful improvements in language (+14.04, P=.0051) and daily functioning (+14.53, P=.0017). All measurements are compared with baseline scores.
“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 2-way crossover study. Each period was 12 weeks in duration with no washout between periods. The study enrolled 30 adults age 18 to 41 with FXS caused by >200 CGG repeats in the FMR1 gene. Participants received daily oral doses of 25 mg twice a day of PDE4D allosteric inhibitor or placebo. The PDE4D allosteric inhibitor was very well tolerated.
Parents/caregivers and physician raters were blinded to treatment. All participants completed both treatment periods, although carryover effects limited the primary statistical analysis to Period 1.
In preclinical studies, PDE4D allosteric inhibitor promoted the maturation of connections between neurons, which is impaired in participants with FXS.
Adam M. Staffaroni, PhD; Elena Tsoy, PhD; Jack Taylor, BS; Adam L. Boxer, MD, PhD; and Katherine L. Possin, PhD
Carlos E.V. Sollero, MD; Hsin-Pin Lin, MD; Miguel Chuquilin, MD; James Wymer, MD; and Aaron M. Carlson, MD
Julio C. Rojas, MD, PhD