) Significance: Non-tuberculous mycobacteria (NTM) respiratory infections is increasing across the globe. In the US, in those over 65 years-old, annual prevalence of pulmonary NTM disease increased significantly from 20 to 47 cases/100,000 between 1997-2007 with Hawaii having the highest prevalence at 396 cases/100,000. Pulmonary NTM is 1.4 times more common in women. These numbers are likely underestimated because of a lack of mandatory reporting in the U.S. Treatment 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 drugs. The only oral drugs with reliable activity against M. abscessus complex an NTM are the macrolides and clofazimine. Similar to that for M. avium complex, clofazimine was found to synergize with clarithromycin or amikacin against M. abscessus Clofazimine is an attractive agent for treatment of NTM respiratory infections including M. abscessus but cutaneous and internal organ accumulation from high oral doses cause significant toxicity. High oral doses are required to reach effective concentrations in the lungs. Inhaled doses of clofazimine have the potential to reach immediate treatment concentrations in the lungs with inhaled low doses that do not have significant systemic toxicity. Preliminary Data: Aerophase 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 toxicity. The 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 regions. The Aerophase inhaled aerosol delivery method holds great promise to mitigate toxicity and allow for safe clofazimine administration directly targeted to the site of infection.
Specific Aims :
The first aim of this project is to treat NTM respiratory infections with inhaled clofazimine much more effectively than oral clofazimine with much lower inhaled dose.
The second aim i s to develop a small pocket sized metered dose inhaler with drug formulation, aerosol size, and dose optimized to treat NTM respiratory infections.
The third aim will test in-vivo efficacy of inhaled clofazimine in combination with other drugs.

Public Health Relevance

Non-tuberculous mycobacterial (NTM) respiratory infections is increasing rapidly throughout the world from a wide variety of sources such as treated water, swimming pools, hot tubs, showers, fish tanks, and medical devices. There are limited treatment options for non-tuberculous mycobacterial lung disease for several reasons including side effects from currently available antibiotics and difficulty in the antibiotics reaching all the lungs at effective treatment levels. Aerophase has developed an inhaled antibiotic treatment for NTM and other mycobacterial respiratory infections that has demonstrated effective treatment levels throughout the lungs with low dose to eliminate noticeable side effects.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Small Business Innovation Research Grants (SBIR) - Phase I (R43)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Boyce, Jim P
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Aerophase, Inc.
United States
Zip Code