In an 8-to-3 vote, the U.S. Food and Drug Administration’s (FDA’s) Oncologic Drug Advisory Committee (ODAC) decided against recommending approval of quizartinib for patients with relapsed/refractory FLT3-ITD acute myeloid leukemia (AML).
The second-generation tyrosine kinase inhibitor (TKI) met the primary endpoint for improvement in overall survival (OS), compared with chemotherapy, in its pivotal, randomized, phase III trial. However, in their review of the data, ODAC members could not determine that the benefits of quizartinib treatment outweighed its risks.
The drug was associated with a six-week improvement in OS, but the panel cited a lack of similar improvement in other efficacy measures, including event-free survival, in its decision. Together with concerns about quizartinib’s cardiac-related adverse events and the credibility and generalizability of the trials’ data. For example, 23% of patients assigned to the chemotherapy group did not receive study treatment and were not followed, compared with 2% of patients assigned to the quizartinib group. This disparity “is quite bothersome as to whether this is an adequate and well-controlled study,” said the FDA’s Richard Pazdur, MD, director of the agency’s Oncology Center of Excellence.
Daiichi-Sankyo, the manufacturers of quizartinib, responded that it was unable to follow certain patients who opted to be treated outside of the study’s protocol due to discrepancies in international and regional regulations governing the withdrawal of consent.
The FDA is not required to follow the ODAC’s recommendations, but the agency often adheres to its decisions. The FDA is set to issue its decision on quizartinib’s application by August 25.