Cystic fibrosis patients who were enrolled in Insmed’s two clinical trials, CLEAR-108 and CLEAR-110, continue to see improvements in their infections with Pseudomonas aeruginosa by taking once-daily inhaled Arikace. “In the patients who were on liposomal amikacin [Arikace] for 18 months–6 months in the original trial and 12 months in the extension–we are seeing a sustained improvement in lung function,” said Diana Bilton, MD, from Imperial College London, at the American Thoracic Society annual meeting and quoted in a news story.
These improvements were in the form of positive gains in forced expiratory volume in one second (FEV1) and reductions in P. aeruginosa colonies. “There was a half-log reduction after 6 months, and we see a gradual wane of effectiveness out to one year, but certainly no increase in colonies from baseline,” said Dr. Bilton.
Positive results come as little surprise: interim reports of CLEAR-110 indicated patients had improved FEV1 levels, and these were patients who took advantage of an extension from the successful CLEAR-108 trial. CLEAR-108 originally studied 129 cystic fibrosis patients taking Arikace and 137 cystic fibrosis patients taking the leading cystic fibrosis drug, tobramycin. Of these patients, 80 continued to take Arikace and 88 continued switched to Arikace for the open-label extension CLEAR-110 trial.
“We are not seeing anything in this report that is unexpected,” said Denis Hadjiliadis, MD, from the University of Pennsylvania Health System. “The main benefit that liposomal amikacin has when compared to tobramycin is that the liposomal formula can be administered once a day.” Patients in the trials received 590 mg inhaled Arikace once daily using an investigational nebulizer system. They received up to 12 cycles of 28-day treatment paired with 28-day off-treatment.
Cystic fibrosis medications are often aimed at battling infection with P. aeruginosa, the bacterium that causes chronic lung infection and severe lung damage. “Where amikacin will fit in the treatment of cystic fibrosis is uncertain,” said Dr. Hadjiliadis. “I think it will depend on the cost of the drug and whether the convenience of once-daily treatment will outweigh increased costs. However, all these drugs are expensive, so I don’t think that amikacin–if it is approved by the FDA–will be that much more expensive than tobramycin.”
The FDA put a damper on efforts in July 2011 while investigators researched long-term animal carcinogenicity. In 2012, the hold on clinical trials for Arikace was lifted, and the FDA granted Arikace Orphan Drug Status to treat cystic fibrosis patients with P. aeruginosa infection. Now, it seems Insmed has developed a therapeutic with lasting benefits that will add another much-needed treatment to clinicians’ arsenals against cystic fibrosis lung infections.