Patient Death Pauses Another AML Trial

Clinical Trial Stop_Compressed

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Following the death of a patient, Magenta Therapeutics placed a hold Wednesday on the Phase I/II dose-escalation trial of its acute myeloid leukemia (AML) therapy.

The fatality occurred at the Cohort 3 level of the trial, where participants received MGTA-117 at a 0.08-mg/kg dose. The patient in question developed a grade 5 serious adverse event of respiratory failure and cardiac arrest resulting in death, deemed possibly related to the study drug.

Magenta reported the incident to the FDA as a Suspected Unexpected Serious Adverse Reaction. The decision to pause the study is voluntary and in accordance with the recommendations of the trial’s safety Cohort Review Committee.

The company is currently analyzing the totality of the data and evaluating the best way to continue the development of MGTA-117.

Shares of Magenta dropped 25% in post-market trading Wednesday. 

Magenta’s most advanced oncology candidate, MGTA-117, is an antibody-drug conjugate targeting the CD117 receptor and carrying an alpha-amanitin payload. CD117 is found on hematopoietic stem cells, progenitor cells and cancer blast cells. Meanwhile, α-Amanitin is a highly toxic substance extracted from the death-cap mushroom and is known to kill cancer cells.

By bringing these two elements together in one molecule, MGTA-117, acts as a targeted conditioning therapeutic and selectively depletes CD117-bearing cells in the blood or bone marrow before patients receive gene therapies or undergo stem cell transplantation. In turn, MGTA-117 reduces or completely eliminates the need for chemotherapy.

Patient Deaths Mar AML Drug Development

In the quest for effective and innovative treatments for AML, several biopharma companies have recently hit a snag.

In August 2022, fellow Massachusetts-based company Foghorn Therapeutics encountered a patient death that pushed the FDA to put its Phase I dose-escalation AML study on full clinical hold. Foghorn was trialing FHD-286, a BRG1/BRM inhibitor. The death was due to fatal differentiation syndrome.

Four months earlier, in April 2022, Curis’ oral emavusertib was placed on partial hold after a patient in the Phase I/IIa dose-escalation TakeAim Leukemia study died from several complications, including rhabdomyolysis, a known dose-limiting toxicity of emavusertib. The FDA requested additional safety and efficacy data from Curis.

The FDA put a partial hold on Kura Oncology’s Phase Ib AML trial in November 2021 following a patient death, also linked to fatal differentiation syndrome. Kura’s AML hopeful is KO-539, an investigational oral inhibitor of the menin-KMT2A/MLL protein-protein interaction.

The FDA lifted its hold on KO-539 in January 2022. Development of the Foghorn and Curis candidates remains paused.

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