Aradigm Corporation has submitted a marketing authorization request to the European Medicines Agency (EMA) for Linhaliq as a treatment for non-cystic fibrosis bronchiectasis (NCFBE) patients who with a chronic Pseudomonas aeruginosa bacterial lung infection.
The agency has 21 days to decide if the application is complete, after which it will start the review process, according to a company press release.
At the moment there are no approved treatments for NCFBE to prevent or reduce the burden of bronchiectasis driven by lung infections.
Linhaliq, previously known as Pulmaquin, is a liquid mixture of liposomes and the antibiotic ciprofloxacin, which can counter several bacteria, including P. aeruginosa.
Results from two Phase 3 trials supported Aradigm’s marketing authorization application. They evaluated the safety and effectiveness of Linhaliq delivered as a once-a-day inhaled formulation in patients with NCFBE with chronic P. aeruginosa lung infections.
The ORBIT-3 (NCT01515007) trial included 278 NCFBE patients, and ORBIT-4 (NCT02104245) 304. Patients were randomized to receive either Linhaliq or a placebo for 48 weeks — six cycles of 28 days followed by 28 days without dosing.
This was followed by a 28-day open label extension study in which all patients received Linhaliq.
Researchers compared the efficacy of Linhaliq and the placebo with three measures — how long it took for the first pulmonary exacerbation and its severity, as well as how many exacerbations required an antibiotic. Additionally, they assessed improvements in patients’ quality of life.
ORBIT-4 showed that Linhaliq-treated patients had their first pulmonary exacerbation at day 230, compared with day 158 in the placebo group — a significant difference of 72 days’ delay in exacerbations.
During the 48-week treatment period, researchers saw a statistically significant 37 percent reduction in the frequency of pulmonary exacerbations in patients treated with Linhaliq, versus the placebo.
Linhaliq also led to a significant 42 percent decrease in the frequency of pulmonary exacerbations requiring an antibiotic, and a significant 60 percent reduction in the number of severe exacerbations.
In the ORBIT-3 study, Linhaliq-treated patients developed their first pulmonary exacerbation a median of 214 days after treatment started. Those in the placebo group developed the symptoms 78 days earlier, at a median time of 136 days — a difference that failed to reach statistical significance.
Linhaliq was also associated with a 15 percent reduction in the frequency of pulmonary exacerbations and a 22 percent reduction in a need for antibiotics over the 48 weeks, accompanied by a 20 percent decrease in exacerbations’ severity.
The decrease was not statistically significant, compared with the placebo group, however.
Patients’ quality of life was not improved with Linhaliq during the treatment period.
Both ORBIT-3 and ORBIT-4 showed that Linhaliq led to a marked decrease in the bacterial burden of P. aeruginosa by the end of the first treatment cycle. The effect was sustained throughout all of the treatment cycles.
The two Phase 3 studies supported Linhaliq’s safety. There were no detrimental effects on lung function or symptoms of airway irritation, compared with the placebo groups.
The U.S. Food and Drug Administration (FDA) recently denied Aradigm’s New Drug Application (NDA) for Linhaliq in its present form. The company said it remained committed to working with the agency to get Linhaliq approved.
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