Agency asked for re-analysis of certain clinical data and raised issues with dosing and manufacturing.
A.P. Pharma received a complete response letter from the FDA regarding its NDA for APF530 in the prevention of both acute and delayed onset chemotherapy-induced nausea and vomiting (CINV). FDA asked for re-evaluation of certain clinical data and that the firm perform additional nonclinical studies, resolve dosing problems, and fine-tune production. Based on the anticipated time needed to prepare a resubmission, the company does not anticipate the commercial launch of the drug in 2010.
APF530 contains the 5-HT3 antagonist granisetron formulated in the company’s Biochronomer™ drug delivery system, which reportedly allows therapeutic drug levels to be maintained for five days with a single subcutaneous injection. Injections and oral tablets containing granisetron are approved for the prevention of acute onset CINV but not for delayed onset CINV.
FDA did not request additional clinical efficacy studies but did ask that select existing Phase III trial data be re-presented and re-analyzed. It also requested that the company perform two studies relating to bioavailability and metabolism. Additionally, the agency did not accept A.P. Pharma’s request to waive the requirement for a thorough QT study.
FDA also expressed concerns relating to A.P. Pharma’s two-syringe administration system, including potential issues with the transfer of material from one syringe to the other syringe prior to patient administration, certain components used in the dosing system, and the potential risk of improper administration of the drug product.
Finally, with regard to the chemistry, manufacturing, and control of the product, FDA identified certain deficiencies after inspecting A.P. Pharma and several of its contract manufacturing facilities. The firm must resolve these deficiencies for approval. The agency also requested clarification and revision of certain analytical specifications proposed in the NDA.
A.P. Pharma says that, upon FDA’s request, it had previously demonstrated that terminal gamma irradiation is a feasible approach to enhance the assurance of sterility, and the agency now requests that the firm change to terminal sterilization prior to approval.