FDA lifts clinical hold on Foghorn AML study

June 5, 2023

Foghorn Therapeutics announced this week that the FDA has lifted the clinical hold on its phase 1 study of its acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) drug.

The dose escalation study of FHD-286 was paused last year due to a patient death potentially caused by differentiation syndrome. Differentiation syndrome is associated with the use of AML/MDS therapeutics that prompt the maturation of undifferentiated cancer cells.

The phase 1 study of FHD-286 enrolled 40 patients with relapsed and/or refractory AML and MDS, who had exhausted all other treatment options. The cohort patients included 36 with relapsed and/or refractory AML and four with relapsed and/or refractory MDS.

In response to the FDA hold, Foghorn established an independent adjudication committee of leading AML experts, who concluded that the rate of differentiation syndrome was 15% (six patients out of 40) and classified one case as definitive for differentiation syndrome but not contributing to the patient’s death.

Foghorn says it has worked with the FDA to amend the trial protocols, and as of June 1, 2023, the hold has been lifted and the company intends to start a phase 1 clinical trial. This trial will evaluate the use of FHD-286 in combination with either decitabine or low-dose cytarabine specifically in patients with relapsed and/or refractory AML.

FHD-286 is a drug that can be taken orally and works by inhibiting two specific proteins called BRG1 and BRM. These proteins drive a complex called BAF, which is responsible for regulating the structure of DNA. By blocking the activity of BRG1 and BRM, FHD-286 can interfere with the functioning of the BAF complex.