Pfizer has withdrawn its leukemia drug gemtuzumab ozogamicin (Mylotarg) from the U.S. market at the request of the FDA, following a clinical trial that raised doubts about its efficacy and safety.
The drug, intended for the treatment of acute myeloid leukemia (AML), had been regarded as a promising therapy and was approved in May 2000 under the agency's accelerated approval program. (See ASH: Mylotarg Boosts AML Disease-Free Survival)
But in a subsequent clinical trial, the FDA said, the drug was associated with an increased risk of serious side effects and did not offer a clinical benefit when combined with chemotherapy.
Even at the initial approval, the drug was associated with an increased rate of hepatic veno-occlusive disease, which can be fatal, and the FDA said the rate has only increased in the subsequent trial.
The drug "was granted an accelerated approval to allow patient access to what was believed to be a promising new treatment for a devastating form of cancer," said Richard Pazdur, MD, of the FDA's Center for Drug Evaluation and Research.
"However, a confirmatory clinical trial and years of postmarketing experience with the product have not shown evidence of clinical benefit in patients with AML," Pazdur said in a statement.
Under the accelerated approval program, the FDA can allow a drug to be used to treat serious diseases with an unmet medical need based on a surrogate endpoint -- a laboratory measurement or a physical sign instead of a clinically meaningful endpoint, such as survival.
The initial approval for gemtuzumab was based on the proportion of patients whose disease responded -- decreased or disappeared in laboratory tests -- among 142 patients across three clinical trials.
But under the program, the company was required to conduct additional clinical trials after approval and -- if the trials fail to confirm a clinical benefit -- the agency can withdraw the drug from the market using expedited procedures.
Gemtuzumab was approved to treat patients ages 60 or older with recurrent AML who were not considered candidates for other chemotherapy.
The drug's developer, Wyeth (now part of Pfizer), began a postapproval trial in 2004 that was designed to see if adding gemtuzumab to standard chemotherapy led to a survival benefit in AML patients.
The trial was stopped early when no improvement in clinical benefit was observed, and after a greater number of deaths occurred in the group of patients who received gemtuzumab compared with those receiving chemotherapy alone, the FDA said.
Because of the withdrawal, gemtuzumab is no longer commercially available to new patients, although patients currently taking the drug can finish treatment after consulting with their doctors.