Linhaliq is the new name given Pulmaquin (DRCFI, for Dual Release Ciprofloxacin for Inhalation), being developed by Aradigm. An experimental inhaled therapy, Linhaliq combines the antibiotic ciprofloxacin with a slow-release formulation of liposomal dissolved in an aqueous solution. Ciprofloxacin is a widely prescribed antibiotic for acute lung infections with broad-spectrum antibacterial activity primarily against Pseudomonas aeruginosa, a strain often found in lung infections in bronchiectasis patients.
Pulmaquin, the treatment’s original trade name, was rejected after the U.S. Food and Drug Administration (FDA) found it too similar to other lung disease treatments. The name Linhaliq has received conditional FDA approval.
Linhaliq was evaluated in two Phase 3 clinical trials to assess its safety and effectiveness as a once-a-day inhaled treatment for non-cystic fibrosis bronchiectasis patients with chronic Pseudomonas aeruginosa infections.
These trials, ORBIT-3 (NCT01515007) and ORBIT-4 (NCT02104245), consisted of two identical, worldwide, double-blind and placebo-controlled studies. The duration of each was about one year, and participants received Linhaliq or a placebo once daily in six cycles of 28 treatment days followed by 28 days off-treatment. Both also included an open-label extension, in which all patients received Linhaliq for another 28 days.
Their primary objective was an increase in the median time to a first mild, moderate or severe pulmonary exacerbation or flare. A secondary measure was the frequency of flares throughout the 48-week treatment period.
In ORBIT-4, the median time to the first mild, moderate or severe flare was 230 days in the Linhaliq group compared to 163 days in the placebo group, and a 37 percent reduction in the frequency of flares compared to the placebo. Both outcomes were statistically significant improvements.
In ORBIT-3, the median time to the first mild, moderate or severe flare was 221 days in the Linhaliq group compared to 136 days in those given placebo, a finding that was not statistically significant. The frequency of flares was reduced by 13 percent compared to placebo, also not a statistically significant result.
But the combined analysis of both studies resulted in a statistically significant reduction in the number of flares during the treatment period, representing 27 percent fewer flares over those 48 weeks, and a 33 percent reduction in moderate or severe flares.
The density of Pseudomonas aeruginosa was significantly reduced at the end of the first cycle (day 28) and the magnitude of this effect remained persistent until the end of all treatment cycles.
Linhaliq was safe and well-tolerated in both studies, with no differences seen in lung function or symptoms of airway irritation between Linhaliq and the placebo groups. The most frequent treatment-related adverse events were respiratory in nature.
The FDA designated Linhaliq a Qualified Infectious Disease Product (QIDP) for the treatment of people with non-CF bronchiectasis with chronic Pseudomonas aeruginosa lung infections. The treatment has also been designated an orphan drug status and placed on fast track development by the FDA.
Aradigm and the FDA met in December 2016 and again in March 2017 to discuss the submission of a new drug application (NDA) for Linhaliq. An NDA is a key step toward FDA approval of a drug for sale and marketing in the U.S. The company is also seeking approval of Linhaliq in Europe, and in discussions with the European Medicines Agency (EMA).
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