Amphotericin B (Amp B) has been a gold standard for highly efficacious treatment of systemic fungal and parasitic infections with more than a 50-year history of intravenous (IV) formulations, yet no oral formulations are currently commercially available.
The oral Amp B formulation developed by iCo Therapeutics may have significant advantages over an IV formulation with fewer adverse events and an easier way of administration. Assuming that clinical studies will confirm good safety and efficacy results, the oral Amphotericin B could be used in a variety of indications, including prevention of fungal infections in immunocompromised
patients. Historically, the main advantage of Amp B has been lower frequency of interaction with other drugs and a chance of developing drug-resistance to fungal infections.
The early stages of the oral iCo Amp B program involved various formulations of Amp B used in nonclinical models of aspergillosis and candidiasis as well as leishmaniasis. All studies showed good efficacy and safety of the oral Amp B formulations, and the compound selected for further clinical development in capsule form is referred to as iCo-019.
An initial first in man study, a Phase 1 dose-escalation clinical study was carried out in healthy adult volunteers. Study results indicated an excellent safety profile with no serious drug events and no drug-related adverse events in any of the explored doses of Oral Amphotericin B. In addition, a good concentration of the drug was identified in the plasma with a prolonged blood circulation time without the associated gastrointestinal effects or liver and kidney toxicity.
A clinical study using multiple dosing of oral Amp B is in preparation. Using multiple dosing with oral Amp B will provide useful information about general safety and tolerability of repeated oral administration of oral Amp B. It will also provide additional information regarding drug’s amount in the bloodstream (exposure over time) after multiple dosing with oral Amp B formulation.