Shares of Foghorn are tumbling after the FDA placed a full clinical hold on a Phase I dose escalation study that had already been subject to a partial hold following a patient death.
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Shares of Foghorn Therapeutics were falling rapidly in premarket trading Tuesday after the company announced the FDA placed a full clinical hold on a Phase I dose escalation study. The trial had already been subject to a partial hold following a patient death.
The hold was placed on a trial assessing FHD-286, a BRG1/BRM inhibitor, in relapsed and/or refractory acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS), Foghorn said. The partial hold was levied by the FDA following the death of a patient who possibly developed fatal differentiation syndrome, a serious side effect associated with AML, diverse hematological cancer and MDS treatments. The full hold is due to additional suspected cases of fatal differentiation syndrome, the company reported.
The syndrome is caused by a large, rapid release of cytokines from leukemia cells that are affected by many cancer treatments. Foghorn noted in its announcement that differentiation syndrome is believed to be an on-target mechanism for FHD-286.
The regulatory agency made the call following the submission of data in response to the partial hold that was placed on the trial in May.
Foghorn stated that the FDA requires a full analysis of the data before the hold will be lifted and the dose-escalation study allowed to continue. The company had initially planned for data from this study to be available by the end of 2022. However, with the complete clinical hold, that timeline will not likely be met.
In a brief statement, Foghorn CEO Adrian Gottschalk said the company is committed to patient safety and will work with the FDA to address any questions. Gottschalk added that the company will provide the required analysis as quickly as possible in order to resolve the FDA’s questions.
FHD-286 is a potent, selective, allosteric enzymatic inhibitor of BRG1 and BRM, both of which are highly similar proteins that are the “catalytic engines” across all forms of the BAF complex, one of the key regulators of the chromatin regulatory system, Foghorn stated. In preclinical studies, FHD-286 demonstrated anti-tumor activity across a broad range of malignancies including both hematologic and solid tumors.
The company stated that FHD-286, which was developed with its Gene Traffic Control platform, has the potential to be a first-in-class therapeutic. FHD-286 is the first drug candidate developed on that platform that directly targets the chromatin regulatory system.
While the study of FHD-286 is on hold for AML and MDS, Foghorn noted the dose escalation study assessing the drug candidate in metastatic uveal melanoma, a rare eye cancer, will continue per protocol. Uveal melanoma is diagnosed in about 2,000 adults each year in the United States. The disease metastasizes in approximately 50% of cases, leading to very poor prognosis. Data from the Phase I study is expected in the first half of 2023.
Shares of Foghorn closed at $14.59 on Monday but fell more than 30% in premarket trading to $10.27.
