publication date: May. 17, 2019
ODAC votes down AML drug as FDA raises concerns over equipoise, uncertain efficacy
By Paul Goldberg
The FDA Oncologic Drugs Advisory Committee May 14 voted 8-3 against approval of quizartinib for the treatment of adults with relapsed or refractory acute myeloid leukemia which is FLT3- ITD positive, as detected by an FDA-approved test.
Quizartinib, a multikinase inhibitor, is sponsored by Daiichi-Sankyo Inc.
Comments from ODAC members echoed FDA’s concerns about imbalance in withdrawals of patients from the experimental vs. control arm of the pivotal trial of quizartinib. After randomization, 23% of patients withdrew from the control arm. On the experimental arm, patient withdrawals were at 1.6%.
Clinicians testifying for the company said repeatedly that the drug had greater chances of getting FLT3- ITD positive AML patients to transplants. However, getting patients to transplant wasn’t the primary endpoint in the study.
The committee was less concerned about the drug’s cardiotoxicity, finding that it was manageable and less ominous than the risk of death from AML.
Richard Pazdur, director of the FDA Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products, raised questions about the investigators’ equipoise.
“When you have an imbalance of randomized patients, 23% vs. 1.6%—that is quite bothersome,” Pazdur said at the meeting. “When we talk about randomization, we talk about the concept of equipoise, and I think we have to have a discussion: Was there equipoise during the randomization process?
“I’ve been here 20 years, and I haven’t seen this discrepancy of randomized but not treated,” Pazdur said. “And then you get into other confounding issues of censoring that also demonstrate potential imbalance here, that’s quite … Continue reading ODAC votes down AML drug as FDA raises concerns over equipoise, uncertain efficacy
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