Aradigm is asking the U.S. Food and Drug Administration (FDA) for permission to market its candidate therapy, Linhaliq, to treat non-cystic fibrosis bronchiectasis (NCFBE) with chronic lung infections caused by Pseudomonas aeruginosa.
The company’s New Drug Application (NDA) is backed by data from the Phase 3 ORBIT-4 (NCT02104245) and ORBIT-3 (NCT01515007) trials, and from the Phase 2b ORBIT-2 trials. Aradigm’s preclinical and clinical results, as well as data from other publicly available sources are expected to further support Linhaliq’s NDA designation approval, according to a press release.
Formerly known as Pulmaquin or Dual Release Ciprofloxacin for Inhalation (DRCFI), Linhaliq is a mixture of encapsulated and free ciprofloxacin, which itself is an antibiotic with broad-spectrum antibacterial activity. Doctors widely use ciprofloxacin to treat acute lung infections caused by bacteria, including P. aeruginosa.
ORBIT-3 and ORBIT-4 assessed the safety and effectiveness of once-a-day inhaled Linhaliq to treat NCFBE patients with chronic P. aeruginosa lung infections. The trials studied 582 patients who received the investigative medicine or placebo in six 28-day treatment cycles, plus 28 days off treatment. This regimen was followed by a 28-day, open-label extension in which all patients received Linhaliq.
The trials showed that Linhaliq was able to delay a first pulmonary exacerbation compared to the placebo-treated group. In addition, the treatment significantly reduced the density of P. aeruginosa bacteria by the end of the first on-treatment period, or the first 28 days. This anti-bacterial effect was maintained throughout all of the remaining treatment cycles.
These studies also showed that Linhaliq was generally safe and well-tolerated. Researchers reported no significant changes in patients’ lung function or airway irritation compared to the placebo group. The rates of treatment-related adverse events were similar in both arms of the studies.
The FDA has granted Linhaliq orphan drug designation for the management of bronchiectasis, as well as qualified infectious disease product designation for the treatment of NCFBE patients with chronic lung infections caused by P. aeruginosa. Linhaliq has also received FDA fast-track designation.
Aradigm, based in Hayward, California, now plans to submit a marketing authorization application to the European Union for Linhaliq to treat NCFBE patients who have chronic P. aeruginosa lung infections.