Apulmiq, previously known as Linhaliq and Pulmaquin, is a liquid mixture of a slow-release form of liposomes — tiny phospholipid vesicles made of the same material (phospholipids) as the cell membrane — loaded with the antibiotic ciprofloxacin, a widely prescribed antibiotic for acute lung infections.
The therapy acts primarily against the bacteria Pseudomonas aeruginosa, known to cause infections in about one-third of bronchiectasis patients, and associated with a lower quality of life, risk of accelerated lung function deterioration, and more frequent exacerbations than other bacterial strains.
In 2017, Aradigm submitted to the U.S. Food and Drug Administration (FDA) a New Drug Application (NDA) for Apulmiq as a treatment for people with bronchiectasis and chronic Pseudomonas aeruginosa lung infections, based on positive data from the Phase 3 ORBIT-3 (NCT01515007) and ORBIT-4 (NCT02104245) trials.
A response from the FDA issued in January 2018 said that Apulmiq could not be approved in its present form, and indicated concerns related to a manual re-review of exacerbation data and the quality of the product. This followed a recommendation against approval by an FDA advisory committee.
At the time, the FDA recommended an independent third-party verification of the results of the ORBIT trials.
Now, data from the TPE confirmed the effects of Apulmiq in the primary endpoint, or goal, of the ORBIT-4 trial, which was a prolongation of the time to a first pulmonary exacerbation (PE), as well as the study’s secondary goals — the frequency of all PEs and severe PEs. The TPE also verified the previously reported non-significant PE results of the ORBIT-3 trial.
All these endpoints were part of Apulmiq’s original statistical analysis plan. According to an Aradigm press release, the company and the FDA have scheduled a meeting to discuss these trial results now that the TPE has been concluded.
In parallel, the FDA conducted an inspection in January 2018 to audit the Phase 3 trials. In November, a letter from the FDA Division of Clinical Compliance Evaluation said there were no objectionable conditions or practices to justify enforcement action.
Aradigm says it remains confident in Apulmiq’s efficacy, safety, and quality, and will continue pursuing the treatment’s approval in the U.S. In Europe, Apulmiq is being reviewed as a therapy for the same patient population.