Why Arikayce Phase2 Study Will Be Successful? PART 2
vivo. Studies have shown that Arikayce kills NTM bacteria more effectively in cultured lung macrophage. In animal studies, Arikayce was numerically superior to aerosolized amikacin in reduction of bacterial burden.
Meanwhile, the positive phase3 trial of Arikayce in Cystic fibrosis (CF) patients with pseudomonas infections showed (among other things) a reduction of bacterial density. These findings as important proof-of-concept that Arikayce is penetrating the lungs and driving clinical improvements.
In addition, prior studies, though with relatively small sample sizes, have shown the activity of aerosolized amikacin in NTM.
Moreover, the evidence liposomal encapsulation should do better than aerosolized amikacin. Liposomal encapsulation better targets intracellular pathogens.
Roden says the design and formulation of Arikayce has significant advantages. NTM, as an intracellular pathogen, resides and multiplies inside the vacuoles of macrophages in the lung.
Many antibiotics cannot effectively access the subcellular compartment inside macrophages. However, liposomes, which are preferentially taken up by lung macrophage, enable the delivery of high levels of the drug to the compartments where NTM bacteria are located.
Arikayce may achieve even better efficacy than aerosolized amikacin, given the macrophage-targeted delivery and enhanced drug stability by liposomal encapsulation.
Roden said that better delivery increases drug concentration in the lung and treatment compliance. The current amikacin regimen require intravenous administration, which could result in low drug concentration in the disease sites, and undesirable systemic toxicity.
Compared to aerosolized amikacin, liposomal formulation enhances the stability and likely the half-life the antibiotics in vivo; therefore, fewer dosing schedules are needed. The design of Arikayce as a once daily inhalable regimen will promote long-term compliance and thereby increase overall efficacy.