FDA Halts Phase I Trials of Vadastuximab Talirine in AML

Clinical trials of the experimental drug vadastuximab talirine (SGN-CD33A; a CD33-directed antibody drug conjugate) for patients with Acute Myeloid Leukemia (AML) have been placed on hold by the U.S. Food and Drug Administration (FDA). This novel agent had been previously awarded orphan drug status by the FDA and the European Medicines Agency for the treatment of AML.

The trials have been halted after four patients who were treated with vadastuximab talirine along with Allogeneic Hematopoietic Cell Transplant (AHCT), either prior to or following treatment, died. All four of these patients had veno-occlusive disease at the time of death; two additional trial participants also had hepatotoxicity. The possible link between risk of hepatotoxicity and treatment with vadastuximab talirine is being evaluated. In addition, identification of the appropriate protocol revisions are being reviewed.

Consequently, Seattle Genetics, the drug’s manufacturers, have halted any further enrolment of their phase I/II trial clinical trials of vadastuximab talirine in pre- and post-AHCT patients. In addition, a study investigating the combination of vadastuximab talirine with hypomethylating agents in older patients with AML has also been put on hold as well as another study investigating combining the 7+3 chemotherapy with vadastuximab talirine in younger, newly diagnosed AML patients.

Nonetheless, the phase III CASCADE trial in older AML patients and a phase I/II trial in Myelodysplastic Syndrome is still proceeding with enrolment.