FDA Rejects Chemotherapy Nausea Drug
Agency requests new analysis of phase III data (Mar. 28)
The FDA has rejected the new drug application (NDA) for an injectable formulation of granisetron (APF530, A.P. Pharma) for the prevention of chemotherapy-induced nausea and vomiting (CINV). The agency’s Complete Response Letter described the following issues that need to be addressed:
- The FDA has requested a re-analysis of the existing phase III clinical data that reclassify patients into those receiving moderately emetogenic chemotherapy (MEC) and those receiving highly emetogenic chemotherapy (HEC), according to the recently modified American Society of Clinical Oncology (ASCO) 2011 guidelines. The agency did not ask for any new clinical studies.
- The FDA has requested that a human-factors validation study be conducted to evaluate the usability of the APF530 syringe system, together with its proposed product labeling and instructions for use, with the product assembled using a validated commercial process.
- With respect to chemistry, manufacturing, and controls (CMC), the FDA has requested the refinement of one product-quality analytical test method, and has asked that certain deficiencies identified during facility pre-approval inspections be addressed.
APF530 is being developed for the prevention of both acute- and delayed-onset CINV — leading causes of premature discontinuation of cancer treatment. Since only one injectable 5-HT3 antagonist has been approved for the prevention of delayed-onset CINV, this indication represents an area of particular unmet medical need, according to the drug’s developer.
APF530 contains the 5-HT3 antagonist granisetron, formulated in a proprietary drug-delivery system, which allows therapeutic drug levels to be maintained for 5 days with one subcutaneous injection. Currently available intravenous and oral formulations of granisetron are approved only for the prevention of acute-onset CINV.
Source: A.P. Pharma; March 28, 2013.