Target refractory MAC lung disease right where it lives1-3

Depiction of ARIKAYCE1,3,4

Short animation of ARIKAYCE and PULMOVANCE technology

PULMOVANCE
liposome

Amikacin
sulfate

~0.3 μm

Mobile Target Image

PULMOVANCE™

is a unique technology that delivers amikacin sulfate directly to the site of infection1-3

ARIKAYCE delivers:

  • Liposomal and free amikacin into the lungs through nebulization1
  • ~4-fold 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 macrophages5
  • 5 to 8 times more amikacin into pulmonary macrophages compared to inhaled free amikacin in animal studies5
  • Effectively penetrates to get to the site of infection5

The clinical significance of these data is unknown.

More uptake into macrophages as shown in an in vivo study5


ARIKAYCE in vivo amikacin uptake into macrophages in rats compared to inhaled free and IV amikacin5

Macrophages in ARIKAYCE is 17.8, for Inhaled free amikacin is 2.9, and in IV amikacin is 0.1. Airways in ARIKAYCE is 292.6, for Inhaled free amikacin is 142.5, and in IV amikacin is 4.2. Lung tissue in ARIKAYCE is 6917.0, for Inhaled free amikacin is 2771.0, and in IV amikacin is 162.1. And plasma in ARIKAYCE is 3.8, for Inhaled free amikacin is 3.1, and in IV amikacin is 22.6.

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Macrophages in ARIKAYCE is 17.8, for Inhaled free amikacin is 2.9, and in IV amikacin is 0.1. Airways in ARIKAYCE is 292.6, for Inhaled free amikacin is 142.5, and in IV amikacin is 4.2. Lung tissue in ARIKAYCE is 6917.0, for Inhaled free amikacin is 2771.0, and in IV amikacin is 162.1. And plasma in ARIKAYCE is 3.8, for Inhaled free amikacin is 3.1, and in IV amikacin is 22.6.
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

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.5


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*


Mean serum AUC0-24 is the mean serum level under the curve from 0 to 24 hours/ Mean serum Cmax is the maximum serum concentration achieved for one dose. Mean serum under the curve from 0 to 24 hours for ARIKAYCE was 23.5 micrograms per hour per milliliter. Mean serum under the curve for intravenous amikaycin sulfate was 154 micrograms per hour per milliliter. Maximum serum concentration for ARIKAYCE was 2.8 micrograms per milliliter. Maximum serum concentration for intravenous amikaycin sulfate was 76 micrograms per milliliter.

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Mean serum AUC0-24 is the mean serum level under the curve from 0 to 24 hours/ Mean serum Cmax is the maximum serum concentration achieved for one dose. Mean serum under the curve from 0 to 24 hours for ARIKAYCE was 23.5 micrograms per hour per milliliter. Mean serum under the curve for intravenous amikaycin sulfate was 154 micrograms per hour per milliliter. Maximum serum concentration for ARIKAYCE was 2.8 micrograms per milliliter. Maximum serum concentration for intravenous amikaycin sulfate was 76 micrograms per milliliter.
| | 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.

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

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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; MIC=minimum inhibitory concentration.

References:
1. ARIKAYCE [package insert]. Bridgewater, NJ: Insmed Incorporated; 2020. 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. 3. Data on file. Insmed Incorporated. Bridgewater, NJ. 4. 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. 5. 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. 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).
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