FDA Lifts Clinical Hold on Phase 1 AML and MDS Clinical Trial

Effective June 1, 2023, the FDA lifted its clinical hold on Foghorn Therapeutics’ Phase 1 study of FHD-286 dose escalation in patients with acute myeloid leukemia and myelodysplastic syndromes. The announcement recently appeared in Targeted Oncology and described Foghorn’s efforts in pioneering medicines that treat disease by correcting gene expression abnormalities.

Foghorn CEO Adrian Gottschalk said that the company has since amended its protocol.

Additionally, as a result of the FDA clinical hold, Foghorn created an independent adjudication unit of AML experts. The committee found the rate of differentiation syndrome was 15%.

One case was classified as differentiation syndrome, yet it was not associated with the patient’s death. Five cases could not be determined with respect to differentiation syndrome.

Foghorn anticipates beginning a study of FHD-286 combined with cytarabine or decitabine (chemotherapy) on relapsed and/or refractory patients in the third quarter of 2023.

The company’s decision to move on to the combination study was influenced by clinical data confirming FHD-286’s impact as a differentiation agent, together with a safety profile and preclinical combination data.

The Differentiation Syndrome

The FDA hold was announced by Dr. Adrian Gottschalk in August of 2022 as the result of cases of fatal differentiation syndrome possibly associated with FHD-286 therapy. In this regard, differentiation syndrome is defined as a severe reaction to drugs that are used in the treatment of acute myeloid leukemia (AML) and acute promyelocytic leukemia (APL), a type of AML that affects a patient’s bone marrow.

Dr. Eytan Stein, Leukemia Service Chief, and Clinical Investigator, noted that Phase 1 clinical data on dose escalation showed a differentiation effect in patients with various mutations who were heavily pretreated. Dr. Stein stated that even with the current available treatment options there is still an unmet need as the majority of AML patients will relapse.

The FHD-286 Study Data

The Phase 1 study of FHD-286 dose escalation enrolled 40 patients who were heavily pretreated with a minimum of three or more prior lines of therapy. These patients were left with no other options. Two of the study’s goals were tolerability and safety. Most of the participants had poor genetic risk factors and were found to have broad-ranging mutations.

The adverse event profile for FHD-286 in the study was in sync with a patient population that had significantly relapsed or was refractory (not responding) to treatment. The doses were administered orally once daily.

Foghorn has plans to begin its FHD-286 Phase 1 study enrolling relapsed and refractory patients with AML in the third quarter of 2023.

Details of the study include escalation of FHD286 combined with a fixed dose of decitabine or alternatively with a fixed dose of cytarabine in a three plus three dose escalation pattern.

Rose Duesterwald

Rose Duesterwald

Rose became acquainted with Patient Worthy after her husband was diagnosed with Acute Myeloid Leukemia (AML) six years ago. During this period of partial remission, Rose researched investigational drugs to be prepared in the event of a relapse. Her husband died February 12, 2021 with a rare and unexplained occurrence of liver cancer possibly unrelated to AML.

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