Results from Pulmonary Non-Tuberculous Mycobacteria (PNTM) Study Using Aradigm's Liposomal Ciprofloxacin to Be Presented at ICAAC/ICC 2015
Scientists from the Oregon State University, Corvallis (OSU) and Aradigm Corporation (NASDAQ: ARDM) (the "Company") demonstrated that Aradigm's investigational drugs, Lipoquin® and Pulmaquin®, significantly reduced pulmonary non-tuberculous mycobacteria infection (PNTM) with Mycobacterium abscessus using once daily respiratory tract dosing in mice that had established colonization with this microorganism. After 3 weeks of treatment, the number of colony forming units (CFUs) in the lungs was significantly reduced (p<0.05) by 95.2% and 96.1% by Lipoquin and Pulmaquin, respectively; after 6 weeks of treatment, the CFUs were further reduced (p<0.05) by 99.7% and 99.4% for Lipoquin and Pulmaquin, respectively. In contrast, unencapsulated ciprofloxacin had no effect.
"These new findings are important because lung infections with M. abscessus are particularly severe, with major urgent need for more effective therapies. The results also show the potential of Aradigm's liposomal ciprofloxacin against M. abscessus, in addition to the efficacy against M. avium which we reported previously. Our data suggests even more profound effects can be anticipated with treatment over several months as is typically used in human clinical trials," said Dr. Luiz Bermudez, professor of Biomedical Sciences at OSU.
The detailed description of this research and its findings will be presented at Poster Session 084 entitled "Pneumonia" at 11:00 am -1:00 pm on Saturday, September 19, 2015 (Abstract ID/Title: #B-536 - Treatment of Lung Infection Caused by Mycobacterium abscessus in Beige Mice with Pulmonary Delivery of Liposomally Encapsulated Ciprofloxacin is Associated with Significant Reduction of Bacterial Load) at the Interscience Conference of Antimicrobial Agents and Chemotherapy and International Congress of Chemotherapy and Infection (ICAAC/ICC 2015) in San Diego, CA.
The research reported in this publication was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Number R43AI106188. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
About Pulmonary Non-Tuberculous Mycobacteria (PNTM) Infections
NTM is found almost everywhere - for example, in tap water and the soil. People with severe pulmonary diseases including cystic fibrosis, chronic obstructive pulmonary disease (COPD), and Alpha-1 Antitrypsin deficiency are particularly vulnerable to PNTM infections. PNTM symptoms include: fever, cough (including coughing up blood), weight loss/loss of appetite, fatigue and night sweats. Bronchiectasis is a frequent co-morbidity in these patients.
PNTM patients are treated with antibiotics. Some species of mycobacteria may be resistant to certain antibiotics and the antibiotics may cause side effects that require stopping the treatment. Treatment may last more than one year.
A publication from the National Institutes of Health based on U.S. Medicare data from 1997-2007 determined that the annual prevalence of patients infected with PNTM in the U.S. increased 8.2% per year from 20 cases/100,000 to 47 cases/100,000 in people over 65. A 2015 publication from co-authors from several US government departments stated that prior year statistics led to a projected 181,037 national annual cases in 2014 costing the US healthcare system approximately $1.7 billion.
About Aradigm's Pulmaquin and Lipoquin investigational product candidates
Ciprofloxacin, available in oral and intravenous formulations, is a widely prescribed antibiotic. It is used to treat acute lung infections and is often preferred because of its broad-spectrum antibacterial activity against various bacteria, such as Pseudomonas aeruginosa. Pulmaquin is a dual release formulation composed of a mixture of liposome encapsulated and unencapsulated ciprofloxacin. It is being evaluated in two ongoing Phase 3 studies to determine its safety and effectiveness as a once-a-day inhaled formulation for the chronic treatment of non-cystic fibrosis bronchiectasis (non-CF BE).
Following Phase 2a development of the liposomal portion of Pulmaquin (Lipoquin) and Phase 1 development of Pulmaquin, the Phase 2b study ORBIT-2 with Pulmaquin was a 24-week multicenter, randomized, double-blind, placebo-controlled trial in 42 adult non-CF BE subjects. This study demonstrated a significant reduction in P.aeruginosa sputum activity (p=0.002) and a decrease in time to first exacerbation in the per protocol population (p=0.046) and the mITT (p=0.057) populations in the Pulmaquin treated subjects compared to placebo. Overall, the incidence of all treatment emergent adverse events was similar between groups. The most frequently reported treatment related adverse events (reported by ≥ 3 patients in either treatment group) included product taste abnormal and nausea in the Pulmaquin group and wheezing in the placebo group. No serious adverse events were considered treatment related. There were no deaths reported during ORBIT-2.
The Phase 3 clinical program for Pulmaquin in non-CF BE consists of two worldwide, double-blind, placebo-controlled pivotal trials (ORBIT-3 and ORBIT-4) that are identical in design except for a pharmacokinetics sub-study to be conducted in one of the trials. Each trial is enrolling approximately 255 patients into a 48 week double-blind period consisting of 6 cycles of 28 days on treatment with Pulmaquin or placebo plus 28 days off treatment, followed by a 28 day open label extension in which all participants will receive Pulmaquin (total treatment duration approximately one year). The superiority of Pulmaquin vs. placebo during the double-blind period is being evaluated in terms of the time to first pulmonary exacerbation (primary endpoint), while key secondary endpoints include the reduction in the number of pulmonary exacerbations and improvements in the quality of life measures. Lung function is being monitored as a safety indicator.
Aradigm has been granted orphan drug designations for liposomal ciprofloxacin as well as for ciprofloxacin for inhalation for non-CF BE in the U.S. In addition, the U.S. Food and Drug Administration (FDA) has designated Pulmaquin as a Qualified Infectious Disease Product (QIDP). The QIDP designation is granted for treatment of non-CF BE patients with chronic lung infections with Pseudomonas aeruginosa. The QIDP designation made Pulmaquin eligible for Fast Track designation which was granted by the FDA in September 2014.
Aradigm is an emerging specialty pharmaceutical company focused on the development and commercialization of drugs for the prevention and treatment of severe respiratory diseases. Aradigm is currently in Phase 3 development of Pulmaquin (an investigational proprietary formulation of ciprofloxacin for inhalation) for the treatment of non-cystic fibrosis bronchiectasis. Aradigm's inhaled ciprofloxacin formulations are also product candidates for treatment of patients with cystic fibrosis and non-tuberculous mycobacteria, and for the prevention and treatment of high threat and bioterrorism infections, such as inhaled tularemia, pneumonic plague, Q fever and inhaled anthrax. More information about Aradigm can be found at www.aradigm.com.
Except for the historical information contained herein, this news release contains forward-looking statements that involve risk and uncertainties, including those related to the ORBIT-3 and ORBIT-4 clinical trials and the ability to continue successful product development of our potential product candidates, including Pulmaquin, as well as the other risks detailed from time to time in the Company's filings with the Securities and Exchange Commission (SEC), including the Company's Annual Report on Form 10-K for the year ended December 31, 2014 filed with the SEC on March 18, 2015, and the Company's Quarterly Reports on Form 10-Q for subsequent interim periods.
Aradigm, Pulmaquin, Lipoquin and the Aradigm Logo are registered trademarks of Aradigm Corporation.
Nancy Pecota, 510-265-8800
Chief Financial Officer