FDA PI3K Concerns Hits MEI Pharma’s Zandelisib
FDA has discouraged MEI Pharma and Kyowa Kirin from seeking accelerated approval of a BLA for zandelisib, a phosphatidylinositol-3-kinase (PI3K) inhibitor drug candidate for treating patients with B-cell malignancies, based on data from their single-arm Phase 2 TIDAL study. In a recent meeting, FDA told the companies that its position now requires a randomized trial to adequately assess drug efficacy and safety of PI3K inhibitor drug candidates, including zandelisib, according to an MEI release. The agency encouraged the companies to continue efforts with the ongoing, randomized Phase 3 COASTAL study as planned.
FDA’s advice to the companies is in line with recent actions it is taking to step up the review of PI3K inhibitor safety concerns. The agency recently announced that it was convening a 4/21-22 Oncologic Drugs Advisory Committee meeting to review the issue further. Recent concerns stem from a safety alert last month on a possible increased risk of death with TG Therapeutics PI3K inhibitor Ukoniq (umbralisib), which has accelerated approval for treating two specific lymphomas. An agency drug safety communication says FDA has determined that initial findings from a clinical trial evaluating Ukoniq to treat a related type of cancer found a possible increased risk of death in patients taking the drug.
“Because of the seriousness of this concern and the similarities between the two types of cancer for which this drug is approved and the type of cancer that was studied in the clinical trial,” the notice says, “we are alerting patients and healthcare professionals that we are reevaluating this risk against the benefits of Ukoniq for its approved uses.” FDA said it is continuing to evaluate the results from the UNITY trial and has suspended enrollment of new patients in other ongoing clinical trials of Ukoniq while the findings are reviewed.
A recent Federal Register notice indicates that panel members on 4/21 will discuss the “appropriate approach for PI3K inhibitors currently under development in patients with hematologic malignancies and whether randomized data should be required to support a demonstration of substantial evidence of effectiveness and that the drug is safe for its intended use in the proposed population.” On 4/22, they will discuss TG Therapeutics’ supplemental NDA for Ukoniq and a BLA for ublituximab injection. The proposed indication for the two products is a combination use for treating adult patients with chronic lymphocytic leukemia or small lymphocytic lymphoma. Additionally, panel members are scheduled to discuss the existing Ukoniq accelerated approval indications in patients with relapsed or refractory follicular lymphoma and marginal zone lymphoma.