Seattle Genes said today that the FDA has placed clinical retains on several early- to mid-stage trials of vadastuximab talirine (SGN-CD33A) in acute myeloid leukemia (AML) pursuing the deaths of four patients.
A Stage I/II trial of SGN-CD33A monotherapy in pre- plus post-allogeneic transplant AML patients has been placed on full medical hold, while two Phase I trials of the applicant were placed on partial clinical holds consisting of no registration of new patients, though existing patients may continue therapy with reconsent.
The two trials placed on incomplete hold were a study of SGN-CD33A monotherapy, including the subset of older AML patients in combination with hypomethylating real estate agents, and an SGN-CD33A combination treatment with 7+3 radiation treatment in newly diagnosed younger AML patients.
The clinical holds will be in place pending an evaluation from the potential risk of hepatotoxicity in patients who were given SGN-CD33A and received allogeneic stem cell transplant, possibly before or after treatment.
According to Seattle Genetics, the four deaths were among six sufferers who have been identified with hepatotoxicity, including several cases associated with veno-occlusive disease.
“ Seattle Genetics can be working diligently with the FDA to determine whether there is any kind of association between hepatotoxicity and treatment with SGN-CD33A, in order to promptly identify appropriate protocol amendments for patient protection and to enable continuation of these trials, ” the company mentioned in a statement.
Overall, more than 300 sufferers have been treated with SGN-CD33A in various clinical trials. No brand new studies of SGN-CD33A will be initiated until the clinical retains are lifted, Seattle Genetics added.
The particular clinical holds will not affect other ongoing trials associated with SGN-CD33A, including the Phase III CASCADE trial in old AML patients and a Phase I/II trial in myelodysplastic syndrome (MDS). Those studies are proceeding with registration, Seattle Genetics said.
SGN-CD33A is a CD33-targeting antibody-drug conjugate (ADC) candidate that targets CD33, that is expressed on most AML and MDS blast cells. The particular CD33 engineered cysteine antibody is stably linked to a very potent DNA-binding agent called a pyrrolobenzodiazepine (PBD) dimer via site-specific conjugation technology (EC-mAb).
Based on Seattle Genetics, the ADC is designed to be stable within the bloodstream and to release its potent cell-killing PBD realtor upon internalization into CD33-expressing cells.
SGN-CD33A has been granted the Orphan Drug designation of both FDA and the European Commission for the treatment of AML.