Xeris Pharmaceuticals, Inc. – FDA CRL

Xeris Pharmaceuticals, Inc. received a Complete Response Letter (CRL) from the FDA regarding its Supplemental New Drug Application (SNDA) for Gvoke (glucagon) injection. The SNDA sought approval for a new indication as a diagnostic aid to temporarily inhibit gastrointestinal tract movement during radiologic examinations in adults. The FDA could not approve the application in its current form due to significant deficiencies. The primary issues fall under Clinical Pharmacology and Biopharmaceutics, specifically the absence of an adequate scientific bridge between the proposed Gvoke product and the relied-upon listed drug for intravenous administration. Since Gvoke's formulation differs, a biowaiver could not be granted, and existing nonclinical data were deemed insufficient to demonstrate comparable bioavailability. Additionally, Chemistry, Manufacturing, and Controls (CMC) deficiencies were identified, as the submitted data did not adequately support the compatibility and stability of Gvoke for the proposed IV administration. The FDA requires admixture studies using the Gvoke vial formulation, including comparative gelling and agglomeration studies against the relied-upon drug, to confirm product stability. To address these concerns, Xeris must either conduct a new human pharmacokinetic study demonstrating comparable bioavailability or provide a robust scientific justification for formulation differences not impacting in vivo performance. This justification requires comprehensive side-by-side comparisons of formulation, physicochemical data, and detailed rationale. The company is strongly advised to meet with the FDA to discuss their bridging strategy. Other required actions include updating prescribing information, resubmitting the proprietary name, and providing a comprehensive safety update.