A diverse spectrum of antifungal agents are in the preclinical stages of development in the U.S. Those furthest along in the development cycle include a number of amphotericin B formulations and an azole. In the former category, ABLC, ABCD, and Ambisome (TM) have not progressed very far in the U.S. though the latter compound is launched in Europe. A newer amphotericin B product is AmB Hydrosomes, a heparinized nanoparticle formulation produced by Access. In the azole class, Zeneca's D0870 has been reported to be active vs. fluconazole-resistant strains, and is characterized by a particularly long plasma half-life. Amongst new fermentation products, both Merck and Eli Lilly have several echinocandin analogues, inhibitors of beta-glucan synthesis, which are presently under evaluation, although their utility in coccidioidomycosis is questionable. The pradimicins, compounds which bind to the cell wall and cause leakage of cytoplasmic contents, are active against a broad-spectrum of fungi, and should soon enter development. Nikkomycin Z, a natural product that inhibits chitin synthesis, has been shown to be particularly active against Coccidioides immitis and other dimorphic fungi, and appears to have a good safety profile. The latter compound is being considered for development.
Full conference title:
Coccidioidomycosis - Centennial Conference