Harmony Biosciences' Fragile X Trial Fails to Meet Primary Endpoint
Harmony Biosciences faced a significant setback as its pivotal trial for a Fragile X syndrome treatment failed to meet its primary endpoint. The company's $60 million investment in ZYN002, a synthetic cannabidiol, has encountered a major obstacle, casting doubt on the future of the drug candidate.
Trial Results and Placebo Response
The phase 3 registrational trial of ZYN002 missed its primary endpoint, which focused on improvement in social avoidance in patients with complete methylation in the FMR1 gene. Harmony Biosciences attributed this failure to a higher-than-expected placebo response, despite efforts to mitigate this effect through a run-in period designed to manage and exclude placebo responders.
CEO Jeffrey Dayno, M.D., had previously discussed the implementation of this run-in period at a Cantor event earlier this month. The company had kept information about this period confidential during the trial to avoid compromising the study's integrity.
Historical Context and Acquisition
ZYN002, formerly known as Zygel, was acquired by Harmony Biosciences in 2023 as part of its $60 million purchase of Zynerba Pharmaceuticals. The asset had already experienced a setback in a phase 2 trial, failing to outperform placebo on the primary endpoint and three key secondary endpoints. However, evidence of efficacy in a subset of patients with complete FMR1 gene methylation had provided hope for success in the pivotal study.
Financial Implications and Future Prospects
The acquisition deal included potential milestone payments that could have added up to $140 million to the initial $60 million upfront cost. With the trial's failure, the realization of these additional payments seems unlikely.
Harmony Biosciences has not yet commented on the future of ZYN002 but plans to conduct a comprehensive analysis of the full data set. CEO Dayno's statement focused on the company's other programs in or near phase 3 testing, suggesting a potential shift in priorities away from the failed Fragile X candidate.
References
- Harmony's pivotal Fragile X trial flops as high placebo response creates discord
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.
Explore Further
What specific strategies or measures could have been implemented to further mitigate the placebo effect in the trial for ZYN002?
What is the size and growth potential of the target market for Fragile X syndrome treatments, and how does ZYN002 compare to existing options?
Are there alternative therapeutic areas or indications where ZYN002 might still prove effective, based on the existing data?
What are the key clinical and commercial risks associated with acquiring a drug asset that has already failed in earlier trials, as observed in the case of ZYN002?
What impact will this trial failure have on Harmony Biosciences' broader R&D pipeline and its approach to future acquisitions?