Drugs

PI3K Briefing Document Reiterates FDA Concerns

A just-posted advisory committee briefing document reiterates FDA concerns with phosphatidylinositol 3-kinase (PI3K) inhibitors and their approval for treating hematological malignancies, setting the stage for a 4/21 discussion by the agency’s Oncologic Drugs Advisory Committee. Most of FDA’s concerns were outlined in a recent online Lancet Oncology article by FDA Oncology Center of Excellence director Richard Pazdur and other FDA officials, who dismissed (see earlier story) the “current paradigm of using overall response rates in single-arm trials to support accelerated approvals.”

The briefing document criticizes current PI3K inhibitor development programs that did not perform adequate dose exploration which in some cases was further complicated by selecting a single-arm study design for initial registration. “The safety analysis of data from single-arm trials,” it says, “is confounded by the absence of a control, which can pose challenges in accurately attributing AEs [adverse events] to either drug or the underlying disease. Because sponsors may select a dose to achieve the highest ORR [objective response rate] without carefully considering a benefit-risk analysis, toxicities are compounded and may contribute to the worrisome OS [overall survival] results seen repeatedly in multiple RCTs [randomized control trials] of these agents.”

Additionally, the briefing document endorses randomized trials as the “most effective method to control for confounding factors” and because they allow for assessing progression-free survival, overall survival (OS), and patient reported outcomes. It says that “OS data should be fully collected and analyzed, as OS is an important metric in the benefit-risk determination, especially for products with significant toxicity. Randomized trials should be prospectively planned to allow for an adequate assessment of survival and other measurements of clinical benefit. Future studies should be designed with additional opportunities to evaluate patient safety, andthere should be a high likelihood that when a study is completed it can indicate an acceptablebenefit-risk profile, which includes evaluation of the impact on survival as both a safety and efficacy metric.”

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