FDA Approves Elzonris to Treat Rare Blood Cancer

The Food and Drug Administration (FDA) approved Elzonris (tagraxofusp-erzs) infusion for the treatment of blastic plasmacytoid dendritic cell neoplasm in adults and in pediatric patients aged 2 or older, according to the agency.

Blastic plasmacytoid dendritic cell neoplasm, which often presents as leukemia or evolves into acute leukemia, is an aggressive and rare disease of the bone marrow and blood that can affect multiple organs. The disease affects mostly elderly patients, who may not be able to tolerate chemotherapies, and therefore, Elzonris may have a better safety and toxicity profile for this patient population due to its targeted mechanism of action.

"Prior to today's approval, there had been no FDA approved therapies for (blastic plasmacytoid dendritic cell neoplasm),” Richard Pazdur, M.D., director of the FDA's Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA's Center for Drug Evaluation and Research, said in a release.

“The standard of care has been intensive chemotherapy followed by bone marrow transplantation,” he added. “Many patients with (blastic plasmacytoid dendritic cell neoplasm) are unable to tolerate this intensive therapy, so there is an urgent need for alternative treatment options.”

The drug is an IL-3 conjugated truncated diphtheria toxin, which essentially delivers diphtheria toxin to cells that have the IL-3 receptor. Many hematologic malignancies have CD123 expression, but blastic plasmacytoid dendritic cell neoplasm in particular has characteristically high expression. When the diphtheria toxin penetrates a cell, it binds to and ADP-ribosylates elongation factor 2, a factor necessary for protein translation. When the protein synthesis process is inhibited, the cell dies by apoptosis.

The agency based its approval on results from two cohorts of patients — those who received Elzonris in the first-line setting and those with relapsed/refractory disease – in a single-arm clinical trial.

In 13 untreated patients, seven patients (54 percent) achieved complete remission (CR) or CR with a skin abnormality not indicative of active disease. Among the 15 patients with relapsed/refractory blastic plasmacytoid dendritic cell neoplasm, one experienced CR and another with CR with a skin abnormality not indicative of active disease.

Common side effects included capillary leak syndrome (fluid and proteins leaking out of tiny blood vessels into surrounding tissues), nausea, fatigue, swelling of legs and hands, fever, chills and weight increase. The most common laboratory abnormalities were decreases in lymphocytes (a kind of white blood cell), albumin (a protein made by one’s liver), platelets, hemoglobin and calcium, and increases in glucose and liver enzymes.