Harmony Biosciences’ $60 million bet on a once-failed Fragile X candidate has gone off the rails. Two years after picking up ZYN002 despite a midphase flop, the biotech has reported that a registrational trial of the synthetic cannabidiol missed its primary endpoint.
Pennsylvania-based Harmony bagged ZYN002, then called Zygel, in 2023 as part of its acquisition of Zynerba Pharmaceuticals. By then, the asset had already failed to beat placebo on the primary endpoint and three key secondary endpoints in a phase 2 trial. But evidence of efficacy in a subset of patients with complete methylation in the FMR1 gene fueled hopes that the asset could hit the mark in a pivotal study.
Those hopes wilted in the face of phase 3 data Wednesday, when Harmony blamed the failure of its trial to hit the primary endpoint on a higher-than-expected placebo response. The primary endpoint looked at improvement in social avoidance in patients with complete methylation in the FMR1 gene.
Harmony tried to limit the placebo response. Like Zynerba’s phase 2 trial, Harmony’s pivotal study used a run-in period to manage and exclude placebo responders, CEO Jeffrey Dayno, M.D., told analysts at a Cantor event early this month. The biotech withheld information about the run-in period during the trial to avoid compromising the study.
Harmony’s press release lacks a comment on the future of ZYN002 and says the company will carry out a comprehensive analysis of the full data set to better understand the results. But the statement also lacks much cause for optimism about the asset, with Dayno focusing on Harmony’s other programs that are in or near phase 3 testing.
The lion’s share of the potential value of Harmony’s Zynerba buyout is tied to clinical, regulatory and sales milestones. Hitting the milestones would add up to $140 million to the value of the buyout, which cost Harmony $60 million upfront.