Drugs

FDA Questions Data in Daiichi-Sankyo NDA

FDA reviewers are questioning the robustness of data submitted in a Daiichi-Sankyo NDA for quizartinib, indicated for treating adults with relapsed or refractory acute myeloid leukemia (AML) which is FLT3-ITD positive, as detected by an FDA-approved test. In a briefing document released before a 5/14 Oncologic Drugs Advisory Committee reviews the submission, FDA reviewers say that data from a single study was positive, but the significance was marginal and the overall survival (OS) results were not robust. They say that the OS treatment effect “appeared to be driven by the stratum of patients preselected for low-intensity chemotherapy and may have been confounded by imbalances in poststudy therapy, and the results of analyses of other efficacy endpoints were either not statistically significant or provided for a magnitude of effect that might not be considered clinically meaningful. These inconsistencies and imbalances undermine the reliability of the trial results.”

According to the briefing document, the advisory committee is set to discuss (a) whether the OS results from Study AC220-007 are credible, (b) what risk management strategies would be useful to reduce the risks of potentially fatal cardiac toxicity, and (c) whether the small OS advantage for quizartinib outweighs the risks of treatment.

On the safety side, the briefing document says that quizartinib “causes QT prolongation via a unique mechanism, namely IKs blockade. Blockade of IKs by quizartinib results in the potential for fatal cardiac arrhythmias. In Study AC220-007, 27% of patients experienced at least one event of QT-prolongation. When compared to intensive chemotherapy or LDAC, the risk of cardiac events was substantially higher with quizartinib. Across the quizartinib clinical development program, the risk of on-treatment deaths due to cardiac events was estimated as 1-2%. These results occurred despite instructions in the protocol regarding patient management to reduce the risks...”

Gupta Raises Concerns About Overton’s Independence, Ideology

FDA commissioner nominee Heidi Overton’s responses on vaccines, contraception and abortion medication during her 9/24 Senate confirmation hearing raise concerns that ideology could influence her decision-making if she takes over the agency, MSNBC senior medical analyst Dr. Vin Gupta said Friday. Gupta was particularly critical of Overton’

Overton Confirmation Remains Uncertain After Senate Hearing

FDA commissioner nominee Heidi Overton emerged from her Senate confirmation hearing Thursday (see earlier story) without resolving questions about whether she has enough Republican support to advance — and with a rapidly narrowing window for confirmation before the midterm elections. The Senate Health, Education, Labor and Pensions Committee hearing provided few

FDA Classifies Boston Scientific Imager II Catheter Recall as Class I

FDA has classified Boston Scientific's recall of its Imager II Angiographic Catheters as Class I because a manufacturing problem could cause catheter tips to degrade and detach, potentially resulting in life-threatening complications. The agency announced the Class I classification 9/25, updating an Early Alert it issued

FDA Approves Gazyva for Childhood-Onset Idiopathic Nephrotic Syndrome

FDA has approved Roche’s Gazyva (obinutuzumab) for reducing the risk of relapse in adults and children aged 2 and older with frequently relapsing or steroid-dependent, childhood-onset idiopathic nephrotic syndrome who are in remission. The expanded approval covers the use of the CD20-directed antibody beyond its existing

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Gupta Raises Concerns About Overton’s Independence, Ideology

Overton Confirmation Remains Uncertain After Senate Hearing

FDA Classifies Boston Scientific Imager II Catheter Recall as Class I

FDA Approves Gazyva for Childhood-Onset Idiopathic Nephrotic Syndrome