Inhalation Formulation of Itraconazole Receives IND Authorization From FDA

The US Food and Drug Administration (FDA) has approved an Investigational New Drug application for PUR1900 (Pulmazole), an inhaled formulation of itraconazole for the treatment of allergic bronchopulmonary aspergillosis in patients with asthma.

The antifungal drug is being developed by Pulmatrix, Inc., which also announced that the FDA has authorized the initiation of a phase 2 clinical trial.

Allergic bronchopulmonary aspergillosis commonly occurs in individuals with asthma or cystic fibrosis, can include an allergic hypersensitivity response of the immune system to Aspergillus colonization and growth in the airways.

Oral itraconazole (Sporanox) is currently used as a treatment alongside corticosteroids in allergic bronchopulmonary aspergillosis patients. However, its use is limited by “poor bioavailability, variable pharmacokinetics, and toxicity concerns related primarily to the risk of gastrointestinal and cardiac side effects, as well as extensive drug-drug interactions.”

According to the announcement by Pulmatrix, the trial will be initiated in the first half of 2019 and will be a randomized, double-blind, multicenter, placebo-controlled study. The trial will evaluate the safety, tolerability, and pharmacokinetics of the antifungal itraconazole administered as a dry powder for inhalation.

A total of 46 participants include adult patients with asthma and allergic bronchopulmonary aspergillosis. The participants will be randomly assigned (1:1:1:1) into 4 treatment arms at the point of enrollment. In the respective treatment arms, participants will receive 10 mg, 20 mg, or 35 mg of PUR1900 or placebo, administered via once daily dry powder inhalation daily for 28 days.

While the primary objective of the study is to evaluate the safety and tolerability of multiple doses of PUR1900, secondary objectives will include the characterization of pharmacokinetics of inhaled PUR1900 in plasma and sputum and the effect of the study drug on inflammation, pulmonary function, asthma symptoms, and Aspergillus burden in sputum.

"We are very pleased that the FDA review of the IND is complete allowing us to proceed and this important regulatory milestone reinforces Pulmatrix's intention to bring an improved novel therapeutic option to patients suffering from ABPA. This is a critical step in the progression of Pulmazole to bring the product to patients in the US," Robert Clarke, PhD, chief executive officer of Pulmatrix, said in a statement.

PUR1900 is the first inhaled dry powder version of itraconazole. The drug is being developed with the goal of improving upon the safety and efficacy profile associated with oral Sporanox by delivering the drug directly to the lung.

Top line data is expected in the second quarter of 2020.