FDA grants gemtuzumab ozogamicin approval for the treatment of CD33 positive AML

On 1^st September 2017, the U.S. Food and Drug Administration (FDA) granted approval to gemtuzumab ozogamicin for the treatment of adult patients with newly diagnosed CD33-positive Acute Myeloid Leukemia (AML). Mylotarg® was also approved for adults and pediatric patients 2 years and older with Relapsed or Refractory (R/R) CD33-positive AML.¹ According to the drug manufacturers, Pfizer, gemtuzumab ozogamicin “is the first therapy with an indication that includes pediatric AML. It is also the only AML therapy that targets CD33, an antigen expressed on AML cells in up to 90% of patients”.

Gemtuzumab ozogamicin, an Antibody Drug Conjugate (ADC), is an antibody-targeted chemotherapeutic agent consisting of a humanized murine CD33 antibody. Since it is a humanized anti-CD33 monoclonal antibody, it is highly specific for targeting leukemic blasts. Mylotarg® binds to and is internalized by tumor cells expressing CD33. As a result, this ADC can then dispense the anti-tumor antibiotic calicheamicin to CD33-expressing tumor cells.²

Gemtuzumab ozogamicin, was previously approved by the FDA via accelerated review in May 2000 for monotherapy of elderly individuals with relapsed AML, but it was voluntarily withdrawn by the company, Pfizer, from market on October 15^th, 2010 for the treatment of AML patients. However, in February 2017, the AGP reported on the resubmission of a Biologics License Application (BLA), that sought approval of gemtuzumab ozogamicin in combination with daunorubicin and cytarabine for the treatment of adults with treatment-naive CD33–positive AML. The FDA Oncologic Drug Advisory Committee (ODAC) also unanimously voted 6 to 1 in favor of allowing Mylotarg® to be approved for the treatment of newly diagnosed adult patients with de novo CD33-positive AML in July 2017, which was reported here.

The approval by the FDA for gemtuzumab ozogamicin was based on results obtained from the phase III ALFA-701 study (NCT00927498), the phase III AML-19 study, and the phase II MyloFrance-1 study. Data from the ALFA-701 study showed that combination of gemtuzumab ozogamicin with standard chemotherapy regimen in adult newly diagnosed de novo AML patients significantly improved 3-year Event Free Survival (EFS) and Relapse Free Survival (RFS) compared to chemotherapy alone.³

Additionally, findings from the AML-19 study, which compared gemtuzumab ozogamicin  monotherapy to best supportive care in elderly AML patients, showed that Mylotarg® significantly improved the Overall Survival (OS) compared to best supportive care (4.9 vs 3.6 months, HR = 0.69, P = 0.005).⁴

The MyloFrance-1 study in adult patients (n = 57) in first relapse, showed that monotherapy with gemtuzumab ozogamicin resulted in 26% of patients achieving Complete Remission (CR) with a median RFS of 11.6 months.⁵