In adult patients with refractory MAC lung disease,
Culture conversion results that last 15+ months1-3


Nearly one-third of refractory patients culture converted by Month 6 and over half stayed converted1-3

Primary and Secondary Charts

aP<0.0001 vs standard therapy.


In the CONVERT trial, the endpoints of the change from baseline in 6MWT distance and SGRQ did not demonstrate clinical benefit at Month 6.1

CONVERT study design


The efficacy and safety of ARIKAYCE + standard therapy vs standard therapy alone were evaluated in an open-label, randomized (2:1), multicenter, global, Phase 3 trial of 336 adult patients with refractory MAC lung disease.1,2

Primary endpoint1,2

Patients who culture converted by Month 6. Patients needed to achieve their first negative culture by Month 4 to meet the primary endpoint.† Culture conversion was defined as 3 consecutive monthly negative sputum cultures. The study design required 2 or 3 negative sputum samples per month for 3 consecutive months to confirm culture conversion.

Secondary/exploratory endpoints2,3

Patients who remained culture converted 12 months after initial conversion, and 3 and 12 months after treatment ended, along with change from baseline in 6MWT and SGRQ.

Patients were considered to have refractory MAC lung disease if they did not achieve negative sputum cultures after a minimum duration of 6 consecutive months of standard therapy that was either ongoing or had been stopped no more than 12 months before the screening visit.1

Patient selection in the CONVERT trial

Key inclusion criteria4

  • MAC lung disease documented by at least 2 positive cultures (≥1 positive culture within 6 months prior to screening and 1 positive culture at screening with cultures obtained ≥1 month apart)
  • Did not respond to active therapy for ≥6 months. Treatment was either ongoing or had been stopped no more than 12 months before the screening visit
  • Evidence of underlying lung disease, such as nodular bronchiectasis and/or fibrocavitary disease by chest radiography or CT

Key exclusion criteria4

  • Cystic fibrosis
  • MAC lung disease resistant to amikacin (as identified by MIC susceptibility >64 μg/mL)
  • Active pulmonary malignancy (primary or metastatic) or any malignancy requiring chemotherapy or radiation therapy within 1 year before screening or anticipated during study period
  • Acquired and primary immunodeficiency syndrome (eg, HIV-positive patients regardless of CD4 counts)

Key baseline patient characteristics in the CONVERT trial2,5

Scroll to see full chart. ➝

Key baseline patient characteristics in the convert trial
Key baseline patient characteristics in the convert trial
Parameter ARIKAYCE + standard therapy (n=224)
n (%)		 Standard therapy alone (n=112)
n (%)
Gender
Female 165 (73.7) 68 (60.7)
Male 59 (26.3) 44 (39.3)
Underlying lung disease
Bronchiectasis only 146 (65.2) 64 (57.1)
COPD‡ 29 (12.9) 19 (17.0)
COPD‡ and bronchiectasis 22 (9.8) 18 (16.1)
Standard therapy prior to enrollment
On treatment 201 (89.7) 101 (90.2)
Off treatment for at least 3 months 23 (10.3) 11 (9.8)

Summary of standard therapy in the CONVERT trial at baseline


Standard therapy was composed of an antimycobacterial regimen of at least 2 antibiotics based on the 2007 ATS/IDSA Statement or respective local guidelines. These drugs may have included, but were not limited to, azithromycin, clarithromycin, clofazimine, ethambutol, ethionamide, rifabutin, and rifampicin.2,4-6




% of patients with ≤2 or ≥3 drugs in regimen4

of patients with 2 or 3 drugs in regimen 4

ARIKAYCE + standard therapy (n=223)

Standard therapy alone (n=112)

AFTER 6 MONTHS OF TREATMENT FAILURE FOR MAC LUNG DISEASE,
Choose to add ARIKAYCE for your patients1

See MAC inside

Using your smart device, scan the QR code to get an inside view of a MAC lung infection in augmented reality (AR).

Judy, 63-year-old woman (real patient)

ARIKAYCE added to standard therapy after culture positive for >6 months on standard therapy alone and worsening symptoms1
patient-profile-judy

Judy, 63-year-old woman (real patient)

ARIKAYCE added to standard therapy after culture positive for >6 months on standard therapy alone and worsening symptoms1
Past medical history
  • First diagnosed with MAC lung infection in 2008 via bronchoalveolar lavage
  • Failed multiple MAC treatment courses over 12 years
  • Chronic bronchiectasis
Microbiology after standard therapy
  • Sputum AFB positive
  • Amikacin susceptible: MIC 16 µg/mL
  • Clarithromycin susceptible: MIC 2 µg/mL
  • Rifabutin susceptible: MIC 0.5 µg/mL
Symptoms after standard therapy
  • Worsening cough, shortness of breath, and fatigue
ARIKAYCE added to standard therapy1
  • ARIKAYCE (started June 2020)
  • Clarithromycin
  • Rifabutin
Assessment and management after starting ARIKAYCE
  • Developed ringing in ears and hearing loss
    • Temporarily stopped ARIKAYCE
    • Audiology exam results normal several weeks later
  • Restarted ARIKAYCE, which she tolerated
  • Negative cultures for MAC lung disease after 12 months of treatment with ARIKAYCE + standard therapy
Treatment plan
  • Continue MAC treatment and monitor sputum cultures and symptoms1,7
See Judy's story
Individual results may vary.
See Judy's story
See Judy's story

Karen, 73-year-old woman (real patient)

ARIKAYCE added to standard therapy after 8 months of standard therapy alone without culture conversion1
patient-profile-karen

Karen, 73-year-old woman (real patient)

ARIKAYCE added to standard therapy after 8 months of standard therapy alone without culture conversion1
Past medical history
  • Cystic bronchiectasis
  • Extensive airway inflammation
  • MAC lung disease diagnosed in 2015
Microbiology after standard therapy
  • Multiple sputum cultures positive for MAC, even after 8 months of triple antibiotic therapy
Symptoms after standard therapy
  • Cough while supine
ARIKAYCE added to standard therapy1
  • ARIKAYCE (started February 2020)
  • Azithromycin
  • Ethambutol
  • Rifampin
Assessment after starting ARIKAYCE
  • 12 months of negative sputum cultures
Treatment plan
  • Continue to monitor for recurrence of infection7
Individual results may vary.

Elisse, 67-year-old woman (real patient)

ARIKAYCE added to standard therapy after testing positive for MAC infection recurrence1
patient-profile-elisse

Elisse, 67-year-old woman (real patient)

ARIKAYCE added to standard therapy after testing positive for MAC infection recurrence1
Past medical history
  • Diagnosed with MAC lung disease in 2017
  • Non-sustained culture conversion after a year of standard therapy
  • Bronchiectasis with acute exacerbation
Microbiology after standard therapy
  • MAC positive via bronchoalveolar lavage
Symptoms after standard therapy
  • Excessive yellow sputum with cough and wheezing
ARIKAYCE added to standard therapy1
  • ARIKAYCE (started February 2020)
  • Ethambutol
  • Rifampin
  • Azithromycin
Assessment after starting ARIKAYCE
  • Culture negative for MAC infection with the addition of ARIKAYCE
Treatment plan
  • Continue ARIKAYCE and monitor sputum cultures and symptoms1,7
See Elisse's story
Individual results may vary.
See Elisse's story
See Elisse's story

Joan, 72-year-old woman (hypothetical patient)

ARIKAYCE added after 6 months of standard therapy without culture conversion1
patient-profile-joan

Joan, 72-year-old woman (hypothetical patient)

ARIKAYCE added after 6 months of standard therapy without culture conversion1
Past medical history
  • COPD x 8 years
  • Bronchiectasis (fibrocavitary) x 4 years
  • MAC lung disease
Clinical presentation
  • Nonproductive cough x 1 year, without improvement on standard therapy
  • Dyspnea
  • Weight loss (10 lb over the past year)
  • Fatigue x 2 years
Current medications for MAC infection
  • Ethambutol
  • Azithromycin
  • Rifampin
Microbiology
  • Induced sputum cultures and smears consistently positive for MAC
  • Macrolide susceptible: MIC 2.5 µg/mL
  • Amikacin (IV) susceptible
Assessment
  • MAC lung disease refractory to standard therapy
Treatment plan
  • Add ARIKAYCE to multidrug regimen after 6 months of treatment failure1
  • Monitor response and obtain sputum cultures every 1 to 2 months7

William, 49-year-old man (hypothetical patient)

On standard therapy for MAC lung disease for 6+ months. Improved symptoms and culture positive
patient-profile-william

William, 49-year-old man (hypothetical patient)

On standard therapy for MAC lung disease for 6+ months. Improved symptoms and culture positive
Past medical history
  • Severe asthma x 30 years
  • Bronchiectasis x 3 years
  • MAC lung disease
Clinical presentation
  • Improved fatigue since starting standard therapy
  • Anorexia without weight loss
  • Nonproductive cough with 1 episode of hemoptysis over the past 12 months
Current medications for MAC infection
  • Azithromycin
  • Ethambutol
  • Clofazimine
Microbiology
  • Induced sputum cultures and smears positive for MAC
  • Macrolide susceptible: MIC 2.5 µg/mL
  • Amikacin (IV) susceptible
Assessment
  • MAC lung disease refractory to standard therapy
Treatment plan
  • Add ARIKAYCE to multidrug regimen after 6 months of treatment failure1
  • Guidelines recommendation is based on failure to convert sputum cultures after 6 months7

Daniela, 57-year-old woman (hypothetical patient)

On ARIKAYCE + standard therapy for MAC lung disease. Culture negative, but experiencing hoarseness and cough.
patient-profile-daniela

Daniela, 57-year-old woman (hypothetical patient)

On ARIKAYCE + standard therapy for MAC lung disease. Culture negative, but experiencing hoarseness and cough.
Past medical history
  • Severe rheumatoid arthritis x 12 years
  • Interstitial pneumonitis 2 years ago
  • MAC lung disease x 1 year
  • Standard therapy, followed by addition of ARIKAYCE after remaining culture positive on 6 months of standard therapy1
Clinical presentation
  • Dysphonia
  • Onset of cough immediately after ARIKAYCE administration
Current medications for MAC infection
  • Azithromycin
  • Ethambutol
  • Rifabutin
  • ARIKAYCE
Microbiology
  • 2 sets of induced sputum cultures and smears were negative
  • Macrolide susceptible: MIC 2.5 µg/mL
  • Amikacin (IV) susceptible
Microbiology
  • 2 sets of induced sputum cultures and smears were negative
  • Macrolide susceptible: MIC 2.5 µg/mL
  • Amikacin (IV) susceptible
Assessment
  • Because Daniela culture converted on ARIKAYCE but is experiencing cough and dysphonia, treatment will be adjusted to help manage her symptoms
Treatment plan1
  • Bronchodilator use before ARIKAYCE treatment
Additional management strategies8§
  • Lozenges/warm water gargle postdosing/soothing fluid intake
  • Change ARIKAYCE treatment to evening
  • Briefly interrupt ARIKAYCE to help manage some adverse events
Footnotes

*There was up to a 10-week window between screening and baseline during which time some patients may have achieved their first negative sputum culture. At the time of enrollment, 89.9% (302/336) of patients were either on a guideline-based regimen for MAC, or off guideline-based therapy for MAC for less than 3 months.1,4,5

†Culture conversion by Month 6 was a surrogate endpoint.1 Clinical benefit has not yet been established.

‡COPD was derived from the medical history data.2

§Additional management strategies are not included in the ARIKAYCE full Prescribing Information. The data are from a telephone survey of 26 patients prescribed ARIKAYCE conducted during a 2-month period at 2 academic medical centers in the United States. Writing assistance was provided to the authors through funding from Insmed Incorporated. Insmed was not involved with the conceptualization, development, conduct, or analyses of the survey.8

6MWT=6-minute walk test; ATS=American Thoracic Society; CT=computed tomography; HIV=human immunodeficiency virus; IDSA=Infectious Diseases Society of America; ITT=intent to treat; IV=intravenous; MIC=minimum inhibitory concentration; SGRQ=St George's Respiratory Questionnaire.

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. Griffith DE, Thomson R, Flume PA, et al. Amikacin liposome inhalation suspension for refractory MAC lung disease: sustainability and durability of culture conversion and safety of long-term exposure [published online ahead of print April 19, 2021]. Chest. doi:10.1016/j.chest.2021.03.070. 4. 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. Online data supplement. Am J Respir Crit Care Med. 2018;198(12)(suppl):E1-E28. Accessed June 4, 2021. https://www.atsjournals.org/doi/suppl/10.1164/rccm.201807-1318OC/suppl_file/griffith_data_supplement.pdf. 5. Data on file. Insmed Incorporated. Bridgewater, NJ. 6. Griffith DE, Aksamit T, Brown-Elliott BA, et al; ATS Mycobacterial Diseases Subcommittee. An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. Am J Respir Crit Care Med. 2007;175(4):367-416. 7. Daley CL, Iaccarino JM, Lange C, et al. Treatment of nontuberculous mycobacterial pulmonary disease: an official ATS/ERS/ESCMID/IDSA clinical practice guideline. Clin Infect Dis. 2020;71(4):e1-e36. 8. Swenson C, Lapinel NC, Ali J. Clinical management of respiratory adverse events associated with amikacin liposome inhalation suspension: results from a patient survey. Open Forum Infect Dis. 2020:7(4). doi.org/10.1093/ ofid/ofaa079.
Primary endpoint: Culture conversion by 6 months1,2
Primary Endpoint Chart

Patients who met the primary endpoint at Month 6 had to have a first negative culture by Month 41,2

Culture conversion by Month 6 was a surrogate endpoint.1 Clinical benefit has not yet been established.

In the CONVERT trial, the endpoints of the change from baseline in 6MWT distance and SGRQ did not demonstrate clinical benefit at Month 6.1

aP<0.0001 vs standard therapy.

Responder analysis/secondary endpoints:
Percentage of patients who met the primary endpoint and remained culture negative1,3

The proportion of the ITT population (224 for ARIKAYCE + standard therapy vs 112 for standard therapy alone) who remained culture negative 12 months after initial conversion, 3 months after treatment ended, and 12 months after treatment ended was 18.3%, 16.1%, and 13.4% for ARIKAYCE + standard therapy vs 2.7%, 0%, and 0% for standard therapy alone, respectively.1,3

Responser Analysis Chart

a

Percentage of patients remaining culture negative 12 months off all treatment was an exploratory endpoint likely reflecting the natural history of the disease.3

b

Not significant.

c

P<0.002 vs standard therapy.

d

P<0.0001.

ARIKAYCE + standard therapy (n=224)

Standard therapy alone (n=112)

Responder analysis

Purple Lung

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Culture conversion results through 15 months1-3
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Primary endpoint: Culture conversion by 6 months1,2
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Responder analysis/secondary endpoints: Percentage of patients who met the primary endpoint and remained culture negative1,3

The proportion of the ITT population (224 for ARIKAYCE + standard therapy vs 112 for standard therapy alone) who remained culture negative for 12 months after initial conversion, 3 months after treatment ended, and 12 months after treatment ended was 18.3%, 16.1%, and 13.4% for ARIKAYCE + standard therapy vs 2.7%, 0% and 0% for standard therapy alone, respectively.1,2

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% of patients with ≤2 or ≥3 drugs in regimen4
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