FDA Places Full Hold on Foghorn’s Phase I Study in Relapsed/Refractory AML/MDS

The U.S. Food and Drug Administration has placed a full clinical hold on Foghorn Therapeutics’ phase 1 dose escalation study of FHD-286, an inhibitor of BRG1/BRM, in relapsed and/or refractory acute myelogenous leukemia and myelodysplastic syndrome.

Photo: Adrian Gottschalk, CEO of Foghorn Therapeutics

Adult acute myeloid leukemia (AML) is a cancer of the blood and bone marrow and the most common type of acute leukemia in adults. AML is a diverse disease associated with multiple genetic mutations. It is diagnosed in about 20,000 people every year in the United States.

The dose escalation phase 1 study of FHD-286 in metastatic uveal melanoma (mUM) continues per protocol. The company plans to report data from the mUM study in the first half of 2023.

Foghorn is focused on a novel class of medicines targeting genetically determined dependencies within the chromatin regulatory system. Through its proprietary scalable Gene Traffic Control platform, Foghorn systematically studies, identifies, and validates potential drug targets within the chromatin regulatory system.

FHD-286 is a highly potent, selective, allosteric and orally available, small-molecule, enzymatic inhibitor of BRG1 and BRM, two highly similar proteins that are the ATPases, or the catalytic engines across all forms of the BAF complex, one of the key regulators of the chromatin regulatory system. In preclinical studies, FHD-286 has shown anti-tumor activity across a broad range of malignancies including both hematologic and solid tumors.

The full clinical hold in the AML/MDS study is due to the observation, in the data submitted in response to the partial hold, of additional suspected cases of fatal differentiation syndrome believed to be associated with FHD-286. Differentiation syndrome is associated with AML/MDS therapeutics that induce differentiation, an effect that has been seen with, and is believed to be on-target for, the proposed mechanism of action for FHD-286. The FDA has additional questions and requires further analyses before the clinical hold may be lifted.

“We are committed to patient safety and will work with the FDA to address the agency’s questions and provide further analyses to resolve the clinical hold as soon as possible,” said Adrian Gottschalk, CEO of Foghorn Therapeutics.

Author: Rare Daily Staff