AEROPHASE, INC. — Department of Health and Human Services SBIR Phase I: NIAID

Description

Project Summary AbstractDescriptionSignificanceNon tuberculous mycobacteriaNTMrespiratory infections is increasing across the globeIn the USin those overyears oldannual prevalence of pulmonary NTM disease increased significantly fromtocasesbetweenwith Hawaii having the highest prevalence atcasesPulmonary NTM istimes more common in womenThese numbers are likely underestimated because of a lack of mandatory reporting in the U STreatment of non tuberculous mycobacterial lung disease is challenging for several reasons including the relative resistance to currently available drugs and the difficulty in tolerating prolonged treatment with multiple drugsThe only oral drugs with reliable activity against Mabscessus complex an NTM are the macrolides and clofazimineSimilar to that for Mavium complexclofazimine was found to synergize with clarithromycin or amikacin against Mabscessus Clofazimine is an attractive agent for treatment of NTM respiratory infections including Mabscessus but cutaneous and internal organ accumulation from high oral doses cause significant toxicityHigh oral doses are required to reach effective concentrations in the lungsInhaled doses of clofazimine have the potential to reach immediate treatment concentrations in the lungs with inhaled low doses that do not have significant systemic toxicityPreliminary DataAerophase has recently demonstrated that innovative aerosol formulations of clofazimine with a new type of aerosol drug inhaler can treat TB respiratory infections without side effects from systemic toxicityThe new clofazimine formulation and aerosol device has demonstrated sustained pulmonary treatment concentration and an aerosol size range that can target the entire lung with clofazimine even alveolar regionsThe Aerophase inhaled aerosol delivery method holds great promise to mitigate toxicity and allow for safe clofazimine administration directly targeted to the site of infectionSpecific AimsThe first aim of this project is to treat NTM respiratory infections with inhaled clofazimine much more effectively than oral clofazimine with much lower inhaled doseThe second aim is to develop a small pocket sized metered dose inhaler with drug formulationaerosol sizeand dose optimized to treat NTM respiratory infectionsThe third aim will test in vivo efficacy of inhaled clofazimine in combination with other drugs