Apulmiq (ciprofloxacin), previously Linhaliq and Pulmaquin, is an experimental inhaled antibiotic being developed by Savara Pharmaceuticals, which acquired rights to the therapy from Grifols. Aradigm originally developed the treatment.
Doctors currently use oral and injectable formulations of ciprofloxacin to treat respiratory tract infections. Apulmiq is an inhalable form for patients with non-cystic fibrosis bronchiectasis and chronic lung infections due to Pseudomonas aeruginosa bacteria.
How does Apulmiq work?
Ciprofloxacin, the active ingredient in Apulmiq, is a broad-spectrum antibiotic that belongs to the class of quinolone antibiotics. It inhibits enzymes that bacteria require for replication and thereby interferes with the growth of certain bacteria, such as P. aeruginosa.
The inhaled formulation has an advantage over oral and injectable forms by allowing targeted delivery to the lungs. This leads to a high local concentration of the medication in the lungs and a lower concentration in the blood, potentially resulting in fewer side effects.
Apulmiq contains a 1:1 mixture of 20 mg/mL of free ciprofloxacin and 50 mg/mL of liposomes filled with ciprofloxacin. Liposomes are tiny vesicles that consist of the same material as cell membranes. They allow the slow release of the antibiotic, which reduces the dosing frequency. The free ciprofloxacin is available immediately. The recommended dosage of Apulmiq is 6 mL once a day.
Apulmiq in clinical trials
Two randomized, double-blind, placebo-controlled Phase 3 clinical trials, ORBIT-3 (NCT01515007) and ORBIT-4 (NCT02104245), assessed Apulmiq’s safety and effectiveness as a once-a-day inhaled treatment (6 mL) in non-cystic fibrosis bronchiectasis patients with chronic P. aeruginosa infections.
Researchers designed the two trials identically and conducted them over 48 weeks at clinical sites around the world. Participants received Apulmiq or a placebo once daily in six cycles of 28 treatment days, followed by 28 days off-treatment. Both trials included an open-label extension phase, in which all patients received Apulmiq for another 28 days. The primary endpoint 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.
ORBIT-4 included 304 participants. The median time to the first mild, moderate, or severe flare was 230 days in the Apulmiq group and 163 days in the placebo group. Researchers also observed a statistically significant 37% reduction in the frequency of flares in the Apulmiq group compared with the placebo group.
In the ORBIT-3 trial with 278 participants, the median time to the first mild, moderate, or severe flare was 221 days in the Apulmiq group and 136 days in the placebo group, a finding that was not statistically significant. The frequency of flares was reduced by 15% compared to the placebo in the Apulmiq group, also not a statistically significant result.
Based on data from the ORBIT-3 and ORBIT-4 trials, Aradigm submitted a new drug application to the U.S. Food and Drug Administration (FDA) for Alpumiq in 2017. The FDA rejected the application in 2018 due to concerns that included the clinical data, discordant trial results, and product quality. A subsequent review led to a similar decision in February 2019, with the FDA recommending a confirmatory Phase 3 trial. Savara will now work with the FDA to design this clinical study.
Aradigm also submitted a marketing authorization request for Alpumiq to the European Medicines Agency (EMA) in March 2018. The company withdrew this application in October 2019, citing a ruling by an EMA office that trial data for the treatment did not show a “positive benefit-risk balance.”
Last updated: May 13, 2020
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