After its cannabidiol gel candidate failed a phase 3 trial in fragile X syndrome, Harmony Biosciences has now paused development of the asset in a different genetic disease.
Harmony announced in September that ZYN002 failed to improve social avoidance in certain patients with fragile X syndrome, which the company attributed to an unusually high placebo response. As a result, Harmony has halted work on the gel in 22q11.2 deletion syndrome while it reviews all data from the fragile X trial, called Reconnect, according to the biotech's third-quarter earnings release.
"We are conducting an in-depth review of all Reconnect study data," Harmony said in a statement to Fierce Biotech. "Once all datasets are available, we expect to share updates early next year on the Fragile X syndrome study and implications for potentially embarking on a phase 3 study in 22q deletion syndrome."
Pennsylvania-based Harmony picked up ZYN002 in 2023 when it acquired Zynerba Pharmaceuticals. The candidate had already flopped in a phase 2/3 fragile X trial run by Zynerba, but showed signs of efficacy in a subset of patients with complete methylation in the FMR1 gene. Fragile X syndrome is caused by mutations in the FMR1 gene that lead to the gene being overly methylated, which is a process that silences genes so that they don’t produce proteins.
Based on that hint of efficacy, Harmony decided to focus on this patient group in the phase 3 RECONNECT trial, but the asset still failed to hit its primary endpoint.
22q11.2 deletion syndrome is a genetic disease that shares some symptoms with fragile X syndrome—notably cognitive impairment regarding numbers and time—but is caused by a missing piece of chromosome 22.
Zynerba completed a phase 1/2 trial of ZYN002—then called Zygel—in children with 22q11.2 deletion syndrome in 2022. The company said that Zygel led to significant improvement in measures of anxiety, depression and aberrant behavior, with only mild side effects from the application of the gel.
While the fate of the program remains up in the air, the biotech isn't currently running any active trials of ZYN002 in 22q11.2 deletion syndrome, the company confirmed to Fierce.
Besides ZYN002, Harmony has seven other assets in its pipeline, led by pitolisant, which is already approved for narcolepsy as Wakix and is currently being tested in a phase 3 Prader-Willi syndrome trial. The drug was also evaluated in a phase 2 trial for myotonic dystrophy type 1 that wrapped in October 2024.
Harmony also touts late-stage asset EPX-100 (clemizole hydrochloride), which the biotech is running through a pair of phase 3 trials in Dravet syndrome and Lennox-Gastaut Syndrome—both rare forms of epilepsy. Harmony secured EPX-100 through its $35 million upfront acquisition of Epygenix in 2024.