FDA Approves Gemtuzumab Ozogamicin for AML

The U.S. Food and Drug Administration (FDA) approved gemtuzumab ozogamicin (GO) for two indications: adults with newly diagnosed CD33-positive acute myeloid leukemia (AML) and children ≥2 years old with relapsed or refractory CD33-positive AML.

GO initially received accelerated approval in 2000 as a stand-alone treatment for older patients with relapsed CD33-positive AML, but was voluntarily withdrawn from the market after subsequent confirmatory trials failed to verify clinical benefit and demonstrated safety concerns, including a high number of early deaths.

In July 2017, the FDA’s Oncologic Drugs Advisory Committee issued a favorable opinion of GO; the agency approved GO at a lower recommended dose, at a different schedule in combination with chemotherapy or as a single agent, and in a new patient population.

The decision was based on three trials of GO – two investigated GO as a single agent and one investigated GO in combination with chemotherapy.

In the first stand-alone treatment study, patients who received GO had longer overall survival compared with patients who received supportive care (4.9 months and 3.6 months, respectively); in the second study, 26 percent of patients treated with GO achieved a complete remission that lasted a median of 11.6 months.

In the combination study, patients with newly diagnosed CD33-positive AML were randomized to receive GO with or without daunorubicin and cytarabine; patients in the GO arm achieved longer median event-free survival than those on chemotherapy alone (17.3 months vs. 9.5 months; p value not provided).

The most common adverse events associated with GO include pyrexia, nausea, infection, vomiting, bleeding, thrombocytopenia, stomatitis, constipation, rash, headache, elevated liver function tests, and neutropenia. GO will carry a boxed warning for severe or fatal hepatotoxicity, including veno-occlusive disease or sinusoidal obstruction syndrome.

Source: FDA press release, September 1, 2017.