Amphotericin B Formulations – The Possibility of Generic Competition

From the 1950s, Amphotericin B (AmB) in the form of Fungizone® was considered the “gold standard” in antifungal therapy. This was due to its broad-spectrum of activity. In the 1990s, Fungizone® was relegated to a second line treatment option after the commercialization of lipid-based formulations (AmBisome®, Abelcet® and Amphocil®). These new medicines have similar efficacies but more favourable safety profiles. These formulations will be coming off patent over the coming months and so there is an opportunity for generics manufacturers to enter the arena. However, the lack of clear regulatory guidance on how to perform bioequivalence studies with liposomal drugs makes it difficult to ensure that generic parenteral formulations present quality, efficacy and safety profiles similar to the innovator product. To date, AmB therapy relies mostly on parenteral administration although infusion-related side effects and nephrotoxicity can lead to treatment being halted. Non-parenteral AmB administration would potentially lead to safer treatments and expand the benefits of antifungal and antileishmanial therapy with this drug worldwide. Despite real scientific advances in the area over the last ten years, very few delivery systems have progressed from proof-of-concept to clinical trials as oral, topical or pulmonary AmB medicines. Cyclodextrins and nanoparticle based formulations (self-emulsifying systems, cochleates and liposomes) are the most promising delivery systems to date.