Foghorn finally has clear route back to clinic after FDA lifts yearlong hold on blood cancer drug

Foghorn Therapeutics has been sitting in dock for over a year due to an FDA clinical hold placed on its blood cancer drug in the wake of a patient death. Now, the biotech can set sail once again.

A phase 1 trial of FHD-286 in multiple acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) was initially placed on partial hold in May 2022 following the death of a patient with potential differentiation syndrome. The syndrome is associated with AML and MDS drugs that promote differentiation of myeloblasts into mature cells.

The partial hold was upgraded to a full hold in August last year. Since then, Foghorn has amended the trial, and CEO Adrian Gottschalk said in a release Monday morning that the company had worked with the FDA to resolve the regulator's issues “with a focus on patient safety.”

“Clinical data suggest FHD-286 is a potent, broad-based differentiation therapeutic, and we believe it has significant combination potential as a treatment in AML,” added Gottschalk, who expects a new phase 1 study to launch in the third quarter of the year.

In response to the hold, Foghorn established an independent adjudication committee of leading AML experts, which concluded the rate of differentiation syndrome in the paused study had been 15%. While one of these cases was the patient who died, the committee decided that the syndrome did not contribute to the death.

FHD-286 is an enzymatic inhibitor of BRG1 and BRM, two proteins that promote cancer cell growth. The upcoming study will see the drug tested in combination with the chemotherapies Dacogen or cytarabine in relapsed and/or refractory AML patients.

Foghorn isn’t the only drug developer to have seen differentiation syndrome when treating AML and MDS. The FDA put a phase 1b clinical trial of Kura Oncology’s menin inhibitor KO-539 on hold in 2021 after a death potentially linked to differentiation syndrome. Further back, Agios Pharmaceuticals had cases in recipients of enasidenib and ivosidenib, inhibitors of isocitrate dehydrogenase. In all cases, the holds were eventually lifted, with the latter drugs now marketed in the U.S. by Bristol Myers Squibb and Servier, respectively.