A.P. Pharma, Inc. reported positive pivotal phase III results for APF530, the company’s sustained release formulation of ganisetron.

The company's product, APF530, is being developed for the prevention of chemotherapy-induced nausea and vomiting (CINV). APF530 contains granisetron, which blocks a specific receptor found in the gut responsible for triggering CINV. The product is designed to maintain therapeutic drug levels, for prolonged periods of time providing at least five days prevention of CINV. The company's Phase II human clinical trial of APF530 in September 2005 achieved all of its primary and secondary endpoints.

A Phase III clinical trial for APF530 was launched in May 2006 as a multi-center, randomized, observer-blind, actively-controlled, double-dummy, parallel group study comparing the efficacy of APF530 with Aloxi(R). The trial included 1,395 patients treated at 103 centers in the United States, Poland and India. The company completed all patient recruitment in June 2008. Patients were stratified in two groups, one group receiving moderately emetogenic chemotherapeutic agents and the other receiving highly emetogenic chemotherapeutic agents. The patients in each group were randomized to receive in the first chemotherapy treatment cycle either of a high dose of APF530 (10 mg), a low dose of APF530 (5 mg) or the currently approved dose of Aloxi(R). Results showed that the 10 mg dose was more effective than the 5 mg dose and the drug would probably be filed for approval at the higher dose.

The company reported that the treatment hit the primary endpoint in three of four assessments outlined in a Phase III comparison trial with standard therapy. Although the failure of the drug in one of four assessments, A.P. Pharma, stressed the positive and plans to file for an approval.

The company anticipates regulatory approval of APF530 for the prevention of acute and delayed onset CINV for patients undergoing both moderately and highly emetogenic chemotherapy and expects that results will be announced in the third quarter with an new drug application (NDA) filed with the U.S. Food and Drug Administration (FDA) by the end of 2008.

A.P. Pharma is a specialty pharmaceutical company focused on the development of ethical pharmaceuticals utilizing its own polymer-based drug delivery systems. The Company's primary focus is the development and commercialization of bioerodible, injectable and implantable systems under the trade name Biochronomer(TM). Initial target areas of application for the company's drug delivery technology include anti-nausea, pain management, anti-inflammation and DNA/RNAI applications.

APF530 contains granisetron formulated with Biochronomer(TM) polymers and is designed to provide three to five days of continuous relief from chemotherapy-induced nausea and vomiting following a single subcutaneous injection.

Biochronomer(TM) polymers are poly ortho esters that are produced by a condensation reaction between a diketene acetal and polyols. This reaction is highly reproducible and kilogram quantities of GMP (good manufacturing practices) polymer can be produced. Because ortho ester linkages are stable at neutral pH and hydrolyze at increasing rates as the pH at the polymer/water interface decreases, erosion rates of the polymer can be varied within very wide limits by incorporating into the polymer a short segment of poly lactic acid that acts as a latent acid catalyst.

The polymers can be prepared in a variety of physical forms, ranging from hard, glassy materials to materials that are injectable at room temperature by proper selection of diols. Drugs can be incorporated by a simple mixing procedure at room temperature and the formulation is intended to be commercialized in pre-filled, sterile syringes.

The solid polymers are thermoplastic materials and can be easily fabricated by extrusion, injection molding and compression molding. They are also readily soluble in methylene chloride, tetrahydrofuran and ethyl acetate.

A.P. Pharma has completed toxicology studies for its bioerodible polymers. According to the company, the polymers have been shown to be biocompatible and safe. The polymers are stable at room temperature provided they are stored under anhydrous conditions.

Source: A.P. Pharma, Inc.