Mavoglurant in Fragile X Syndrome: Results of two open-label, extension trials in adults and adolescents

Fragile X syndrome (FXS) is the most common monogenic cause of inherited intellectual and
developmental disabilities. Mavoglurant, a selective metabotropic glutamate receptor subtype-5
antagonist, has shown positive neuronal and behavioral efects in preclinical studies, but failed to
demonstrate any behavioral benefts in two 12-week, randomized, placebo-controlled, double-blind,
phase IIb studies in adults and adolescents with FXS. Here we report the long-term safety (primary
endpoint) and efcacy (secondary endpoint) results of the open-label extensions. Adolescent (n=119,
aged 12–19 years) and adult (n=148, aged 18–45 years) participants received up to 100mg bid
mavoglurant for up to 34 months. Both extension studies were terminated prematurely due to lack
of proven efcacy in the core studies. Mavoglurant was well tolerated with no new safety signal. Five
percent of adults and 16.9 percent of adolescents discontinued treatment due to adverse events.
Gradual and consistent behavioral improvements as measured by the ABC-CFX scale were observed,
which were numerically superior to those seen in the placebo arm of the core studies. These two
extension studies confrm the long-term safety of mavoglurant in FXS, but further investigations are
required to determine whether and under which conditions the signifcant preclinical results obtained
with mGluR5 inhibition can translate to humans.