Pulmatrix, Inc. released animal-based research data at the 2015 North American Cystic Fibrosis Conference indicating that PUR1900 (iSPERSE™-formulated itraconazole) helped fight against Aspergillus fumigatus in rats. The fungus causes lung infection in cystic fibrosis. Concentrations of PUR1900 were high in the lungs but low in the overall body of the rats, indicating that the medication works at its intended target and is less likely to affect other bodily systems. The company presented the data at the 2015 North American Cystic Fibrosis Conference in Phoenix, Ariz.
PUR1900 is formulated using Pulmatrix’s proprietary iSPERSE™ (Inhaled Small Particles Easily Respirable and Emitted) dry powder delivery platform. According to a company press release, the technology “seeks to improve therapeutic delivery to the lungs by maximizing local concentrations and reducing systemic side effects.”
The researchers compared PUR1900 to two other antifungal compounds — amphotericin B and voriconazole.
Scientists collected lung and blood plasma samples from the rats five minutes before giving them one of the three medications for a period of seven to fourteen days. They also tested the medications in a petri dish (in vitro) using different types of fungi.
In rat lungs, itraconazole persisted for a long period of time, and cleared out in approximately one week. Amphotericin B lung concentrations also remained constant over a period of one week, but voriconazole was quickly cleared out from the lungs.
The amount of active medication that the researchers were able to obtain from the rat lung tissue for itraconazole was significantly higher when compared to amphotericin or voriconazole. This may mean that itraconazole does not need to be administered as often as the other two medications. All of the medications were able to fight the fungus A.fumigatus when tested in vitro.
“The pharmacokinetics and potency of PUR1900 demonstrate that the drug is likely to achieve the high local concentrations needed to combat fungal infections caused by Aspergillus spp while overcoming oral bioavailability limitations and minimizing systemic side effects such as drug interactions,” remarked David L. Hava, PhD, Pulmatrix’s chief scientific officer.
Dr. Richard Moss, emeritus professor of pediatrics at Stanford University, stated: “Use of new technologies such as iSPERSE™ to deliver high concentrations of inhaled antifungal drugs directly to the lung have the potential to effectively prevent or treat serious fungal infections or allergies while avoiding problems of toxicities or resistance encountered with systemic use of oral or parenteral antifungals.”
Fungal infections are common in people with CF, and may lead to worse overall outcomes in people with the disease. Effective medications for combating CF fungal infections are greatly needed. The preclinical studies PUR1900 are a necessary precursor to eventual testing in human clinical trials.