Harmony’s Experimental Fragile X Therapy Fails in Phase 3

Harmony Biosciences said its experimental therapy ZYN002 failed to meet the primary endpoint of improvement in social avoidance in its phase 3 RECONNECT study in neurodevelopmental disorder fragile X syndrome.

The company attributed the failure to a higher-than-expected placebo response rate.

Fragile X syndrome is a rare genetic condition and the leading known cause of both inherited intellectual disability and autism spectrum disorder. The disorder negatively affects synaptic function, plasticity, and neuronal connections, and results in a spectrum of intellectual disabilities and behavioral symptoms, such as social avoidance and irritability. There is a significant unmet medical need in patients living with Fragile X syndrome, as there are currently no FDA-approved treatments for the disorder.

ZYN002 is the first and only pharmaceutically manufactured synthetic cannabidiol, devoid of THC and formulated as a patent-protected, permeation-enhanced gel for transdermal delivery through the skin and into the circulatory system. The product is manufactured through a synthetic process and is not extracted from the cannabis plant. ZYN002 does not contain THC, the compound that causes the euphoric effect of cannabis, and has the potential to be a nonscheduled product if approved.

Cannabidiol, the active ingredient in ZYN002, has been granted orphan drug designation by the United States Food and Drug Administration and the European Medicines Agency for the treatment of Fragile X syndrome and for the treatment of 22q. Additionally, ZYN002 has received FDA Fast Track designation for the treatment of behavioral symptoms in patients with Fragile X syndrome.

The RECONNECT study was a phase 3, randomized, double-blind, placebo-controlled, multicenter study to assess the efficacy and safety of ZYN002, a pharmaceutically manufactured cannabidiol administered as a transdermal gel to patients with Fragile X syndrome ages 3 to under 30 years old.

“While these results are not what we anticipated, we remain confident in our ability to bring innovative therapies to patients while creating long-term value for shareholders,” said Jeffrey Dayno, president and CEO of Harmony Biosciences. “We have a late-stage, catalyst-rich pipeline with multiple phase 3 programs in the clinic, and continue to be on track to initiate our phase 3 trials for pitolisant high dose in narcolepsy and idiopathic hypersomnia in the fourth quarter of this year.”

Photo: Jeffrey Dayno, president and CEO of Harmony Biosciences