A.P. Pharma's NDA for APF530 in prevention of CINV: FDA issues Complete Response Letter

Mar 19 2010

A.P. Pharma, Inc. (Nasdaq:APPA), a specialty pharmaceutical company, today announced that it received a Complete Response Letter from the U.S. Food and Drug Administration (FDA or Agency) regarding its New Drug Application (NDA) for APF530 in the prevention of both acute and delayed onset chemotherapy-induced nausea and vomiting (CINV). APF530 is a long-acting formulation of granisetron utilizing the Company’s proprietary Biochronomer™ drug delivery system. A conference call has been scheduled for Friday, March 19, 2010 at 9:00 a.m. Eastern Time.

A Complete Response Letter is issued by the FDA's Center for Drug Evaluation and Research when the review of a file is completed and questions remain that preclude the approval of the NDA in its current form. The primary points raised in the FDA Complete Response Letter are discussed below:

Dosing System

• The FDA 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.

Chemistry, Manufacturing and Control

• The FDA has completed inspections of A.P. Pharma and several of its contract manufacturing facilities. The Agency identified certain deficiencies during these inspections, and satisfactory resolution of these deficiencies will be required for approval.
• During the NDA review, the FDA asked that the Company determine if terminal sterilization with gamma irradiation is a feasible approach to enhance the assurance of sterility. A.P. Pharma has subsequently demonstrated that terminal sterilization is feasible, and the FDA has requested the Company change to terminal sterilization prior to approval.
• The FDA requested clarification and revision of certain analytical specifications proposed in the Company’s NDA.

Clinical

• The FDA did not request additional clinical efficacy studies, although the Agency has asked for the re-presentation and re-analysis of select existing Phase 3 clinical trial data.
• The FDA requested the Company perform two studies relating to bioavailability and metabolism. A.P. Pharma believes these studies should be of short duration in normal volunteers.
• The FDA did not accept the Company’s request to waive the requirement for a thorough QT study. A.P. Pharma believes this study should be of short duration in normal volunteers. The Company plans to discuss the design and timing of the study with the FDA.

Some of the FDA’s points were addressed in recent NDA amendments by A.P. Pharma that the Agency did not review prior to issuing the Complete Response Letter. The Company believes that these amendments may address some of the issues raised in the Complete Response Letter. The FDA has indicated that A.P. Pharma may incorporate applicable sections of these amendments by specific reference in its resubmission. The Company will be contacting the FDA to request an End-of-Review meeting to discuss the Complete Response Letter. A.P. Pharma is committed to expeditiously resolving the remaining issues required for FDA approval; however, based on the anticipated time needed to prepare a resubmission, the Company does not anticipate the commercial launch of APF530 in 2010.