HAYWARD, Calif.--(BUSINESS WIRE)--Aradigm Corporation (Nasdaq:ARDM) (“Aradigm” or the “Company”) today announced the dosing of the first patient in the ORBIT-4 (Once-daily Respiratory Bronchiectasis Inhalation Treatment) Phase III pivotal clinical trial of Aradigm’s proprietary formulation of inhaled ciprofloxacin (Pulmaquin®) for the treatment of non-cystic fibrosis bronchiectasis (non-CF BE). ORBIT-4 is the second of the two Phase III pivotal clinical trials Aradigm is conducting with Pulmaquin in non-CF BE. The Company announced the dosing of the first patient in the ORBIT-3 clinical trial in April 2014.
The first patient in ORBIT-4 was dosed by respiratory physician Dr. Shari Brazinsky at the Institute of HealthCare Assessment, Inc. in San Diego. “Pulmonary exacerbations in bronchiectasis patients are always a concern as they have an immediate adverse impact on their lives and further worsen their health long term. A treatment that would cause a reduction in the frequency and severity of pulmonary exacerbations in this disease would be highly desirable,” said Dr. Brazinsky.
“Both of our Phase III trials are now globally proceeding. The QIDP Designation will provide us with the opportunity for expedited regulatory interactions to make a potential new treatment for non-cystic fibrosis bronchiectasis more expeditiously available to many patients with this severe condition,” said Juergen Froehlich, MD, Chief Medical Officer of Aradigm.
The Phase III clinical program for Pulmaquin in 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.
"Our experience from recent international meetings confirms that non-cystic fibrosis bronchiectasis is a serious, growing healthcare problem. The pulmonary infections with Pseudomonas aeruginosa are of particular concern in this patient population. We have established a network of multi-national international collaborations to help us in the execution of the ORBIT-3 and 4 trials," said Igor Gonda, President and CEO of Aradigm.
Bronchiectasis is a severe, chronic and rare disease characterized by abnormal dilatation of the bronchi and bronchioles, frequently associated with chronic lung infections. It is often a consequence of a vicious cycle of inflammation, recurrent lung infections, and bronchial wall damage. Non-CF BE represents an unmet medical need with high morbidity and mortality that affects more than 110,000 people in the U.S. and over 200,000 people in Europe. There is currently no drug approved for the treatment of this condition.
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 Phase III studies to determine its safety and effectiveness as a once-a-day inhaled formulation for the chronic treatment of non-CF BE.
Pulmaquin has been tested in preclinical safety studies (up to 3 months in rodents and 9 months in dogs).
Following Phase 2a development of the liposomal portion of Pulmaquin 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 bronchiectasis 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.
Aradigm has been granted orphan drug designations for inhaled liposomal ciprofloxacin as well as for inhaled free ciprofloxacin for non-CF bronchiectasis 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-cystic fibrosis bronchiectasis (non-CF BE) patients with chronic lung infections with Pseudomonas aeruginosa.
In 2013, Aradigm granted an exclusive, world-wide license for the Company’s inhaled liposomal ciprofloxacin product candidates for the indication of non-CF BE and other indications to Grifols S.A. More information on the terms of this license may be found in the Company’s Annual Report on Form 10-K for the year ended December 31, 2013 filed with the SEC on March 13, 2014.
Aradigm is an emerging specialty pharmaceutical company focused on the development and commercialization of drugs delivered by inhalation for the prevention and treatment of severe respiratory diseases. Aradigm has product candidates addressing the treatment of non-CF BE, cystic fibrosis and prevention of respiratory and other diseases in tobacco smokers through smoking cessation. Aradigm is also developing Pulmaquin and a liposomal ciprofloxacin formulation as potential medications for the prevention and treatment of high threat and bioterrorism infections, such as inhaled tularemia, pneumonic plague, Q fever and inhaled anthrax.
Aradigm has been granted orphan drug designations for liposomal ciprofloxacin for cystic fibrosis (CF) in the U.S. and the E.U., and liposomal ciprofloxacin and free ciprofloxacin for inhalation for the management of bronchiectasis in the U.S.
Disclaimer and Forward-Looking Statements
The facts and figures contained in this news release which do not refer to historical data are “projections and forward-looking statements’”. The words and expressions like “believe”, “hope”, “anticipate”, “predict”, “expect”, “intend”, “should”, “try to achieve”, “estimate”, “future” and similar expressions, insofar as they are related to Aradigm, the prospects for Aradigm’s inhaled ciprofloxacin product formulations to successfully complete clinical trials and to result in approved products, and the ability of Grifols to successfully commercialize these products, are used to identify projections and forward-looking statements. These expressions with respect to Aradigm reflect the assumptions, hypothesis, expectations and anticipations of the management team of Aradigm at the date of preparation of this news release, which are subject to a number of factors that could make the real results differ considerably, such as the uncertainties associated with clinical trials including lack of effectiveness, lack of statistical significance of results, adverse side effects or other safety issues, uncertainties regarding the process of obtaining regulatory approval for the sale of new drugs, uncertainties concerning the development of demand for new products, uncertainties regarding the level of reimbursement for new products, manufacturing and supply issues and the like. Except for the historical information contained herein, this news release contains forward-looking statements that involve risk and uncertainties detailed from time to time in Aradigm's filings with the Securities and Exchange Commission (SEC), including its Annual Report on Form 10-K for the year ended December 31, 2013 filed with the SEC on March 13, 2014, and Aradigm’s Quarterly Reports on Form 10-Q.
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