Aradigm Awarded Grant to Investigate Treatment of Pulmonary Mycobacterial Infections with Ciprofloxacin Therapies

Aradigm Awarded Grant to Investigate Treatment of Pulmonary Mycobacterial Infections with Ciprofloxacin Therapies

The pharmaceutical company Aradigm was recently awarded a two-year Small Business Initiative Research (SBIR) grant to investigate the company’s inhaled liposomal ciprofloxacin products Linhaliq and Lipoquin as a treatment for two pulmonary non-tuberculous mycobacteria (NTM) infections — Mycobacterium avium and Mycobacterium abscessus.

This SBIR grant, totaling approximately $972,000, was awarded by the National Institute of Allergy and Infectious Diseases (NIAID) and the National Institutes of Health (NIH).

The project’s lead investigator is James D. Blanchard, Aradigm’s lead scientist for preclinical development, while Professor Luiz Bermudez from Oregon State University will lead laboratory research.

Ciprofloxacin is a widely prescribed antibiotic often used to treat acute lung infections, including those caused by Pseudomonas aeruginosa, due to its broad antibacterial activity.

Lipoquin is a liposomal formulation of ciprofloxacin, and Linhaliq (formerly known as Pulmaquin) is a mixture of liposome encapsulated and unencapsulated ciprofloxacin.

According to Aradigm, NTM infections are a significant cause of morbidity among older adults in the United States. From 1997 to 2007, the annual prevalence of these infections reportedly increased from 20 to 47 cases per 100,000 people. In 44% of these NTM infection cases, patients also had bronchiectasis, which suggests an important comorbidity.

NTM infections are also common in patients with other lung diseases, such as cystic fibrosis and emphysema.

The new SBIR grant builds upon encouraging results from previous studies on Lipoquin and Linhaliq, which were supported by a previous SBIR grant. These studies showed that both formulations had a significant efficacy against M. avium complex and M. abscessus infections.

In this project, the effectiveness of Lipoquin and Linhaliq will be evaluated in combination with other compounds, including clarithromycin, amikacin, and ethambutol for M. avium complex infection, and with linezolid and imipenem for M. abscessus infection.

Antibiotic resistance also will be researched.

“Pulmonary infections with non-tuberculous mycobacteria (NTM) have become a serious growing public health problem in the U.S. and many other countries as they can result in debilitating lung disease and are costly to treat. We have shown that lung-delivered liposomal ciprofloxacin is effective in vitro and in animal models of NTM without causing the emergence of resistant NTM,” Bermudez said in a press release.

“Patients with NTM at present typically have to use several antibiotics to avoid the emergence of resistance. This NIH grant is important as it enables us to compare the benefits of lung-delivered liposomal ciprofloxacin alone or in combination with other antibiotics,” Bermudez added.

Aradigm has successfully completed two Phase 3 clinical trials with Linhaliq in patients with non-cystic fibrosis bronchiectasis who had chronic lung infections with P. aeruginosa (NCT01515007 and NCT02104245), and submitted a new drug application to the U.S. Food and Drug Administration (FDA) for Linhaliq in July 2017.

Once-daily inhaled Lipoquin was evaluated in a Phase 2 trial (NCT00889967) in patients with non-cystic fibrosis bronchiectasis patients.

“Bronchiectasis and chronic lung infections with Pseudomonas aeruginosa and NTM are frequent co-morbidities. It is our goal to deliver a much needed new treatment for these patients with severe lung diseases,” Blanchard said.