Photo by Bill Branson
Vials of drug
The US Food and Drug Administration’s (FDA) Oncologic Drug Advisory Committee (ODAC) has announced a positive opinion of gemtuzumab ozogamicin (GO, Mylotarg), a drug that was withdrawn from the US market in 2010.
In a vote of 6 to 1, the ODAC concluded that trial results suggest a favorable risk-benefit profile for low-dose GO given in combination with standard chemotherapy to patients with newly diagnosed, CD33-positive acute myeloid leukemia (AML).
The ODAC’s role is to provide recommendations to the FDA. The FDA is expected to make a decision on the biologics license application (BLA) for GO by September 2017.
With this BLA, Pfizer is seeking approval for GO in 2 indications.
One is for GO in combination with standard chemotherapy (daunorubicin and cytarabine) for the treatment of previously untreated, de novo, CD33-positive AML.
The other is for GO monotherapy for CD33-positive AML patients in first relapse who are 60 years of age or older and who are not considered candidates for other cytotoxic chemotherapy.
GO is an investigational antibody-drug conjugate that consists of the cytotoxic agent calicheamicin attached to a monoclonal antibody targeting CD33.
GO was originally approved under the FDA’s accelerated approval program in 2000 for use as a single agent in patients with CD33-positive AML who had experienced their first relapse and were 60 years of age or older.
In 2010, Pfizer voluntarily withdrew GO from the US market due to the results of a confirmatory phase 3 trial, SWOG S0106.
This trial showed there was no clinical benefit for patients who received GO plus daunorubicin and cytarabine over patients who received only daunorubicin and cytarabine.
In addition, the rate of fatal, treatment-related toxicity was significantly higher in the GO arm of the study.
However, results of subsequent trials suggested that a lower dose of GO was safer.
The current BLA for GO includes data from such a study, known as ALFA-0701.
The ODAC voted that results from ALFA-0701 demonstrated a favorable risk-benefit profile for GO when the drug was given at 3 mg/m² on days 1, 4, and 7 in combination with daunorubicin and cytarabine.
The BLA for GO also includes Pfizer-sponsored studies from the original new drug application for GO and a meta-analysis of patients in 5 randomized, phase 3 studies (including ALFA-0701). These studies span 10 years of research and include more than 4300 patients.
