• Decrease font size
  • Return font size to normal
  • Increase font size
U.S. Department of Health and Human Services

About FDA

  • Print
  • Share
  • E-mail

Gemtuzumab Ozogamicin

On June 21, 2010, Pfizer Inc., in agreement with the FDA, announced that the commercial marketing of Mylotarg (gemtuzumab ozogamicin) will be voluntarily discontinued, and the new drug application (NDA) for Mylotarg will be withdrawn as of October 15, 2010.  Mylotarg will remain available commercially now for a short time to allow patients currently receiving Mylotarg the option to complete their planned course of therapy. Patients who are currently receiving Mylotarg may complete their therapy following consultation with their physicians. New patients should not be prescribed Mylotarg.  Mylotarg will be available for investigational use as provided through the investigational new drug (IND) application process. Ongoing trials of Mylotarg in the U.S. should be conducted under IND. 

Mylotarg was approved in 2000 as a single agent under the category of "accelerated" approval in patients with acute myelogenous leukemia (AML) experiencing their first leukemia relapse and who were 60 years of age and older and who were not considered candidates for other cytotoxic chemotherapy, based on response rates from three pilot studies initially reporting on 142 patients.  With accelerated approval, further study is required to verify and describe clinical benefit for the drug, and approval may be withdrawn if post-marketing study fails to verify clinical benefit. Recently, the post-approval trial intended to provide this necessary confirmatory evidence did not demonstrate clinical benefit for Mylotarg. The trial, S0106, conducted by the Southwest Oncology Group, compared (1) the effect on the complete response rate of the addition of Mylotarg to standard induction chemotherapy alone and (2) the effect on the disease-free survival of a post-consolidation randomization to Mylotarg or no additional therapy. Adults (age 18-60 years) with previously untreated de novo AML were eligible.

At a planned interim analysis in August 2009, the complete response rates were 66% (150/277) on the Mylotarg plus chemotherapy arm and 69% (159/229) on the chemotherapy alone arm. Also, for patients receiving Mylotarg, disease-free survival was not improved. Further, among all patients evaluable for early toxicity, the rate of fatal induction phase toxicity was significantly higher with the addition of Mylotarg, 5.7% (16/283) versus 1.4% (4/281) for patients receiving chemotherapy alone. [BLOOD 2009; 114: abstract 790].

Other recently published trials (British MRC AML-15 and the Hovon-43 trials) have also failed to confirm clinical benefit for Mylotarg as part of induction therapy or in maintenance therapy of AML and found no improvement in measures of survival.

In addition to lack of evidence of efficacy and the increased induction phase mortality observed above, Mylotarg is associated with serious hepatotoxicity including the syndrome of veno-occlusive disease (VOD) which has substantial morbidity and mortality. At the time of the approval, the estimated incidence of VOD was 1%.  A subsequent post-marketing observational study by Wyeth led to a label revision in 2006 describing a 10% occurrence rate, which was even higher in patients who also received a hematopoietic stem cell transplant before or after receiving Mylotarg.

The lack of evidence to confirm clinical benefit and safety concerns have altered the benefit/risk assessment unfavorably for Mylotarg and have led to this decision to withdraw the accelerated approval for Mylotarg.

Link to FDA Press Release:  http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm216448.htm

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System by completing a form online at http://www.fda.gov/medwatch/report.htm, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).