ARIKAYCE targets MAC at the site of infection1-3

MAC can persist in biofilms or intracellularly within macrophages.4

mac can persist in biofilms or intracellularly with macrophages

Challenges to treating MAC4:

  • Effective delivery and distribution of high amounts of antibiotics to the lungs
  • Penetration of biofilms and macrophages to reach the sites where MAC lives and replicates
  • Limit systemic exposure

ARIKAYCE was developed to penetrate biofilm and kill MAC1,3-5:

amikacin liposome inhalation suspension and pulmovance technology

ARIKAYCE delivers1,4:

  • Liposomal and free amikacin into the lungs through nebulization1
  • ~4 times more amikacin into macrophages compared to cells exposed to the same concentrations of free amikacin based on in vitro data from a study of cultured human macrophages4

The clinical significance of these data is unknown.

In the 2018 CLSI guidelines, the MIC breakpoint for resistance is ≥128 μg/mL for ARIKAYCE6

An amikacin MIC level of ≤64 μg/mL is considered susceptible for ARIKAYCE.6

More uptake into macrophages with ARIKAYCE as shown in an in vivo study4

ARIKAYCE in vivo amikacin uptake into macrophages in rats compared to inhaled free and IV amikacin4

Values represent AUC calculated for each group using the mean concentrations at each time point. AUC2-24 was calculated for macrophage, airway, and plasma exposures, whereas AUC0-24 was calculated for lung exposure.4

In vivo study results

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In vivo study results
ARIKAYCE Inhaled free amikacin IV amikacin
Macrophages 17.8 2.9 0.1
Airways 292.6 142.5 4.2
Lung tissue 6917.0 2771.0 162.1
Plasma 3.8 3.1 22.6

The clinical relevance of this is unknown.


Limited systemic exposure with ARIKAYCE1


Following 3 months of once-daily inhalation of 590-mg ARIKAYCE in MAC patients, the mean serum AUC0-24 and Cmax were measured and compared with the approved dosage of 15 mg/kg IV amikacin once daily in healthy adults.




Amikacin serum levels were lower with ARIKAYCE vs IV amikacin1*

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Mean serum level results
Mean serum level results
| | ARIKAYCE | IV amikacin sulfate | |--------------------|----------------|---------------------| | Mean serum AUC0-24 | 23.5 mcg*hr/mL | 154 mcg*hr/mL | | Mean serum Cmax | 2.8 mcg/mL | 76 mcg/mL |

The clinical relevance of this is unknown.


See how ARIKAYCE works


How to Use Your Lamira Nebulizer System for ARIKAYCE
  • Place ARIKAYCE vial at room temperature 45 minutes before use
  • It is recommended to use a bronchodilator before using ARIKAYCE
  • Shake ARIKAYCE vial well before opening it
  • Pour ARIKAYCE into the medication reservoir
  • Begin treatment by pressing and holding the on/off button
  • When ARIKAYCE mist begins to flow, insert the mouthpiece and take slow, deep breaths. Then breathe normally
  • Clean handset and aerosol head immediately after use
Footnotes

*The maximum Cmax and AUC0-24 were below the mean Cmax of approximately 76 mcg/mL and AUC0-24 of 154 mcg*hr/mL observed for IV administration of amikacin sulfate for injection at the approved dosage of 15 mg/kg once daily in healthy adults.1

†Range: 8.0 to 46.5 mcg*hr/mL; n=12.1

‡Range: 1.0 to 4.4 μg/mL; n=12.1

AUC=area under the curve; CLSI=Clinical and Laboratory Standards Institute; IV=intravenous.

References
1. ARIKAYCE [package insert]. Bridgewater, NJ: Insmed Incorporated; 2023. 2. Griffith DE, Eagle G, Thomson R, et al; CONVERT Study Group. Amikacin liposome inhalation suspension for treatment-refractory lung disease caused by Mycobacterium avium complex (CONVERT): a prospective, open-label, randomized study. Am J Respir Crit Care Med. 2018;198(12):1559-1569. doi:10.1164/rccm.201807-1318OC 3. Data on file. Insmed Incorporated. Bridgewater, NJ. 4. Zhang J, Leifer F, Rose S, et al. Amikacin liposome inhalation suspension (ALIS) penetrates non-tuberculous mycobacterial biofilms and enhances amikacin uptake into macrophages. Front Microbiol. 2018;9:915. doi:10.3389/fmicb.2018.00915. 5. Olivier KN, Griffith DE, Eagle G, et al. Randomized trial of liposomal amikacin for inhalation in nontuberculous mycobacterial lung disease. Am J Respir Crit Care Med. 2017;195(6):814-823. doi:10.1164/rccm.201604-0700OC 6. Woods GL, Wengenack NL, Lin G, et al. Performance Standards for Susceptibility Testing of Mycobacteria, Nocardia spp, and Other Aerobic Actinomycetes. Clinical and Laboratory Standards Institute. 1st ed. CLSI supplement M62. 2018:38(22).