Vadastuximab talirine


Vadastuximab talirine or SGN-CD33A is an antibody-drug conjugate or ADC directed to CD33 or Siglec-3 is a transmembrane receptor expressed on cells of myeloid lineage. The trial drug, being developed by Seattle Genetics and currently in clinical trials, is designed for the treatment of acute myeloid leukemia.

Target, mAb, linker, and cytotoxin

The drug target, CD33, is expressed on most AML cells. The CD33 antibody is attached to a highly potent DNA binding agent, a pyrrolobenzodiazepine dimer, via a proprietary site-specific conjugation chemistry via a cleavable maleimidocaproyl type linker, to a monoclonal antibody with engineered cysteines. Vadastuximab talirine contains two site-specific drug attachment engineered cysteines. This use of engineered cysteine residues at the sites of drug linker attachment results in a drug loading of approximately 2 PBD dimers per antibody. PBD dimers are significantly more potent than systemic chemotherapeutic drugs and the site-specific conjugation technology allows uniform drug-loading of the cell-killing PBD agent to the anti-CD33 antibody.

Clinical trials

The drug has concluded phase I clinical trials for Acute myeloid leukemia. Interim results were presented in Dec 2014. and published April 2015.
Based on interim data from ongoing phase I clinical trials presented at the 57th Annual Meeting of the American Society of Hematology, researchers at Seattle Genetics have planned a phase III clinical trial to begin in 2016. This phase III study is expected to evaluate vadastuximab talirine in combination with hypomethylating agents in previously untreated older AML patients. The drug is also being evaluated broadly across multiple lines of therapy in patients with myeloid malignancies, including in ongoing and planned phase I and II clinical trials for newly diagnosed or relapsed AML and for newly diagnosed myelodysplastic syndrome or MDS.

Orphan drug designation

Vadastuximab talirine was granted orphan drug designation by both the U.S. Food and Drug Administration and the European Commission for the treatment of AML.