Liposomal formulation specifically designed to target MAC in the lungs1-3

The clinical relevance of this is unknown.

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ARIKAYCE is designed to deliver amikacin directly to the site of infection via inhalation1-3

The primary mechanism of action of ARIKAYCE is the disruption and inhibition of protein synthesis in the target bacteria by binding to the 30S ribosomal subunit.1

Amikacin is a polycationic, semisynthetic, bactericidal aminoglycoside. Amikacin enters the bacterial cell by binding to negatively charged components of the bacterial cell wall, disrupting the overall architecture of the cell wall.1

ARIKAYCE utilizes PULMOVANCE™ technology consisting of amikacin sulfate encapsulated in liposomes1,3

Depiction of ARIKAYCE1,3,6

ARIKAYCE is an antibacterial drug that is composed of small, charge-neutral, biocompatible liposomes that encapsulate amikacin.1,6

Learn how PULMOVANCE technology works

ARIKAYCE penetrates macrophages and biofilms where MAC resides2,4

MAC bacteria can persist within pulmonary macrophages and can assemble in biofilm colonies in the lungs4,5

MAC bacteria can exist both extracellularly and intracellularly, as planktonic mycobacteria, in lung tissue and intracellular pulmonary compartments (like macrophages), or in biofilm colonies in the mucus and alveolar walls in the lung tissue. There, MAC can subvert normal cellular defense mechanisms, replicate, and cause chronic infections.4,5,7-11

Macrophage icon

In vivo and in vitro data showed an increase in amikacin uptake into macrophages with ARIKAYCE compared to non-liposomal amikacin4

The clinical relevance of this is unknown.

Image of ARIKAYCE (amikacin liposome inhalation suspension) free amikacin and liposome-encapsulated amikacin sulfate. Image of ARIKAYCE (amikacin liposome inhalation suspension) free amikacin and liposome-encapsulated amikacin sulfate.

ARIKAYCE delivers liposomal and free amikacin into the lungs through nebulization.1

Image of ARIKAYCE (amikacin liposome inhalation suspension) delivering amikacin into a macrophage. Image of ARIKAYCE (amikacin liposome inhalation suspension) delivering amikacin into a macrophage.

ARIKAYCE delivered ~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 macrophages.4

Image of ARIKAYCE (amikacin liposome inhalation suspension) liposomal amikacin in a pulmonary macrophage, along with Mycobacterium avium bacteria. Image of ARIKAYCE (amikacin liposome inhalation suspension) liposomal amikacin in a pulmonary macrophage, along with Mycobacterium avium bacteria.

ARIKAYCE delivered 5-8 times more amikacin into pulmonary macrophages compared to inhaled free amikacin in animal studies.4

Image of ARIKAYCE (amikacin liposome inhalation suspension) penetrating MAC biofilm. Image of ARIKAYCE (amikacin liposome inhalation suspension) penetrating MAC biofilm.

ARIKAYCE penetrated biofilm in a study of MAC biofilms.4

The clinical relevance of this is unknown.

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Methodology for in vitro analysis

Cultured human macrophages were exposed to increasing concentrations of fluorescently labeled ARIKAYCE or fluorescently labeled free amikacin.4

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Methodology for in vivo analysis

Rats were inoculated (via nasal inhalation) with either ARIKAYCE or free amikacin.4

The clinical relevance of this is unknown.

ARIKAYCE is associated with limited systemic exposure1,2

There is low systemic exposure to amikacin following the administration of ARIKAYCE.1,2,4,6

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.* The peak amikacin serum levels at steady state were at least 4-fold lower than the estimated minimum Cmax observed with typical IV amikacin doses. Additionally, pharmacokinetic parameters at steady state indicate that there is little accumulation of amikacin, even after 168 days of daily ARIKAYCE administration.1,2

Amikacin serum levels were lower with ARIKAYCE vs IV amikacin1

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Mean serum AUC0-24 was 23.5 mcg*hr/mL with ARIKAYCE (amikacin liposome inhalation suspension) vs 154 mcg*hr/mL with IV amikacin sulfate. Mean serum Cmax was 2.8 mcg/mL with ARIKAYCE vs 76 mcg/mL with IV amikacin sulfate.

The clinical relevance of this is unknown.

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; IV=intravenous; MAC=Mycobacterium avium complex.

References

  1. ARIKAYCE [package insert]. Bridgewater, NJ: Insmed Incorporated; 2018.
  2. Griffith DE, Eagle G, Thomson R, et al. 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. 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):1-12. doi:10.3389/fmicb.2018.00915.
  5. Hall-Stoodley L, Lappin-Scott H. Biofilm formation by the rapidly growing mycobacterial species Mycobacterium fortuitum. FEMS Microbiol Lett. 1998;168(1):77-84.
  6. 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.
  7. Park HY, Jeong B-H, Chon HR, Jeon K, Daley CL, Koh W-J. Lung function decline according to clinical course in nontuberculous mycobacterial lung disease. Chest. 2016;150(6):1222-1232.
  8. Ganbat D, Seehase S, Richter E, et al. Mycobacteria infect different cell types in the human lung and cause species dependent cellular changes in infected cells. BMC Pulm Med. 2016;16:19. doi:10.1186/s12890-016-0185-5.
  9. Rao SP, Ogata K, Catanzaro A. Mycobacterium avium-M. intracellulare binds to the integrin receptor ∂vß3 on human monocytes and monocyte-derived macrophages. Infect Immun. 1993;61(2):663-670.
  10. McGarvey J, Bermudez LE. Pathogenesis of nontuberculous mycobacteria infections. Clin Chest Med. 2002;23(3):569-583.
  11. Qvist T, Eickhardt S, Kragh KN, et al. Chronic pulmonary disease with Mycobacterium abscessus complex is a biofilm infection. Eur Respir J. 2015;46(6):1823-1826.