Magenta Therapeutics has placed an immediate pause on the Phase I/II dose-escalation trial of its AML therapy following the unfortunate death of a patient. The decision to halt the trial came on Wednesday, and was taken as a precautionary measure to ensure the safety of all participants.
Tragically, a participant in Cohort 3 of the trial, who had been receiving a 0.08-mg/kg dose of MGTA-117, suffered a grade 5 serious adverse event of respiratory failure and cardiac arrest, ultimately resulting in death. This event has been deemed possibly related to the study drug.
Magenta has taken the proactive measure of voluntarily pausing a study, in accordance with the recommendations of the trial’s safety Cohort Review Committee, after having reported a Suspected Unexpected Serious Adverse Reaction to the FDA.
The company is delving deep into the data and exploring the possibilities for the further development of MGTA-117. They are carefully evaluating the options, striving to identify the best path forward.
Wednesday saw a dramatic plunge of 25% in Magenta’s share price in post-market trading, sending investors into a tailspin.
Magenta’s most ambitious oncology project to date is MGTA-117, an antibody-drug conjugate designed to target CD117 receptors found on hematopoietic stem cells, progenitor cells, and cancer blast cells. The unique payload of MGTA-117 is the powerful and deadly α-Amanitin, an extract of the death-cap mushroom with a proven ability to eradicate cancer cells.
MGTA-117 is revolutionizing the field of stem cell transplantation and gene therapy by combining two powerful elements into one molecule. This targeted conditioning therapeutic selectively depletes CD117-bearing cells in the blood or bone marrow, making chemotherapy unnecessary in many cases. By drastically reducing the toxicity of these treatments, MGTA-117 is setting a new standard of care for patients undergoing stem cell transplantation and gene therapy.
Patient Deaths Mar AML Drug Development
In the pursuit of revolutionary treatments for Acute Myeloid Leukemia, biopharma companies have recently encountered a roadblock. Despite the promise of new and effective therapies, progress has been stifled. Undeterred, these companies are forging ahead to develop groundbreaking treatments for this devastating condition.
In August 2022, Massachusetts-based Foghorn Therapeutics encountered a tragic event that led to the FDA placing its Phase I dose-escalation AML study on full clinical hold. The cause? A patient death due to fatal differentiation syndrome, resulting from the company’s BRG1/BRM inhibitor, FHD-286. It was a sobering reminder that even the most promising treatments can come with unseen risks.
In April 2022, Curis’ oral emavusertib was placed on partial hold after a patient in the Phase I/IIa TakeAim Leukemia study tragically passed away due to a series of complications, including rhabdomyolysis. This dose-limiting toxicity of emavusertib led to the US Food and Drug Administration requesting additional safety and efficacy data from Curis.
In November of 2021, the FDA placed a partial hold on Kura Oncology’s Phase Ib trial for their highly-anticipated AML hopeful, KO-539. A potential oral inhibitor of the menin-KMT2A/MLL protein-protein interaction, the trial was put on hold after a patient death linked to fatal differentiation syndrome.
After months of waiting, the FDA finally lifted its hold on KO-539 in January 2022, offering hope for the potential of this drug. However, the development of Foghorn and Curis candidates remains paused for the time being.