Gemtuzumab ozogamicin (Mylotarg, Pfizer) is returning to the market in the United States after a 7-year absence, following its approval today by the US Food and Drug Administration (FDA).
The drug has been approved for use in the treatment of adults with newly diagnosed acute myeloid leukemia whose tumors express the CD33 antigen (CD33-positive AML).
The drug has also been approved for the treatment of CD33-positive AML in both pediatric and adult patients who have experienced a relapse or who have not responded to initial treatment.
Although the drug had previously been approved for use in CD33-positive AML, the FDA notes that "today's approval includes a lower recommended dose, a different schedule in combination with chemotherapy or on its own, and a new patient population."
The product is a recombinant, humanized anti-CD33 monoclonal antibody that is attached to the cytotoxic antitumor antibiotic calicheamicin. The antibody binds to and is internalized by tumor cells expressing CD33 antigen, and it delivers the attached calicheamicin to CD33-expressing tumor cells.
Gemtuzumab ozogamicin received an accelerated approved from the FDA in 2000 for use as a stand-alone treatment for older patients with CD33-positive AML who had experienced a relapse. However, the drug was voluntarily withdrawn from the market in 2010, at the request of the FDA, after subsequent confirmatory trials failed to verify clinical benefit and demonstrated problems regarding safety, including a high number of early deaths.
Since then, however, a number of clinical trials initiated by clinical researchers have shown benefit with the drug, and hematologists argued that a reconsideration may be warranted, especially because the drug had shown a survival benefit, as previously reported by Medscape Medical News.
"Mylotarg's history underscores the importance of examining alternative dosing, scheduling, and administration of therapies for patients with cancer, especially in those who may be most vulnerable to the side effects of treatment," commented Richard Pazdur, MD, 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.
He noted that the FDA approval has come after "a careful review of the new dosing regimen, which has shown that the benefits of this treatment outweigh the risk."
Details of Efficacy and Safety Data
The agency noted that efficacy data in adults come from a trial of 271 patients with newly diagnosed CD33-positive AML. The patients were randomly assigned to receive either gemtuzumab ozogamicin in combination with daunorubicin and cytarabine or the combination of daunorubicin and cytarabine.
The primary endpoint was event-free survival (EFS), which was nearly doubled with the new drug (median EFS, 17.3 months vs 9.5 months).
The product was investigated as a stand-alone treatment in two separate trials.
The first trial included 237 patients with newly diagnosed AML who could not tolerate or chose not to receive intensive chemotherapy. Patients were randomly assigned to receive treatment with gemtuzumab ozogamicin or best supportive care. Median overall survival was improved to 4.9 months vs 3.6 months.
The second trial was a single-arm study that included 57 patients with CD33-positive AML who had experienced one relapse of disease. Patients received a single course of gemtuzumab ozogamicin. The endpoint was complete remission, which was achieved by 26% of patients and lasted a median 11.6 months.
The FDA notes that common side effects of gemtuzumab ozogamicin include pyrexia, nausea, infection, vomiting, bleeding, thrombocytopenia, stomatitis, constipation, rash, headache, elevated values on liver function testing, and neutropenia. Severe side effects include low blood counts, infections, liver damage, hepatic veno-occlusive disease, infusion-related reactions, and hemorrhage.
The prescribing information includes a boxed warning that severe or fatal liver damage (hepatotoxicity), including blockage of veins in the liver (veno-occlusive disease or sinusoidal obstruction syndrome), occurred in some patients who took gemtuzumab ozogamicin.
Cite this: Mylotarg Approved for AML: Drug Returns to Market - Medscape - Sep 01, 2017.