Insmed Incorporated announced that late-breaking data from the ARISE study of ARIKAYCE® (amikacin liposome inhalation suspension) were presented at the American Thoracic Society (ATS) 2024 International Conference in San Diego. Data from ARISE evaluating patients with newly diagnosed or recurrent nontuberculous mycobacterial (NTM) lung infection caused by Mycobacterium avium complex (MAC) who had not received antibiotics for their current infection were presented in an oral session and during the ATS Breaking News session "Clinical Trial Results in Pulmonary Medicine. As previously announced, data from ARISE demonstrated that the Quality of Life-Bronchiectasis (QOL-B) respiratory domain may be an effective patient-reported outcome (PRO) tool in patients with MAC lung disease.

The ARISE study was designed to help support the validation of a PRO tool to be used in ENCORE, the ongoing Phase 3b registrational study evaluating the efficacy and safety of an ARIKAYCE-based regimen in patients with newly diagnosed or recurrent MAC lung disease who have not received antibiotics for their current infection. In ARISE, ARIKAYCE-treated patients performed better than those in the comparator arm (a macrolide-based multi-drug regimen) as measured by the QOL-B instrument, with 43.8% of patients achieving an improvement in QOL-B respiratory score above or equal to the estimated meaningful within-subject score difference of 14.8, compared with 33.3% of patients in the comparator arm. While the study was not powered to show a statistically significant difference between treatment arms, a strong trend toward significance was observed for improvement from baseline at Month 7 (least-squares mean change from baseline 12.24 vs.

7.76, p=0.1073). New data presented showed that patients in the ARIKAYCE treatment arm experienced continued improvement in QOL-B scores to Month 7, which included one month off treatment (observed mean QOL-B score change from baseline: 14.1). In contrast, in patients randomized to the comparator arm, QOL-B scores plateaued between Month 3 and Month 6 and worsened after stopping treatment at Month 6 through Month 7 (observed mean QOL-B score change from baseline: 6.9).

In a separate abstract presented, microbiologic evaluation of sputum samples showed that a greater proportion of patients treated with the ARIKAYCE plus macrolide-based background regimen achieved culture conversion by Month 6 versus patients in the comparator arm (80.6% vs. 63.9%, p=0.0712). Patients in the ARIKAYCE arm also achieved nominally statistically significantly higher culture conversion rates at Month 7 versus patients in the comparator arm (78.8% vs.

47.1%, p=0.0010) with culture conversion more likely to persist by Month 7. Of those patients who achieved culture conversion by Month 6, more patients in the ARIKAYCE arm achieved culture conversion by Month 1 versus the comparator arm (74.3% vs. 46.7%, respectively) and median time to first culture conversion event was 1.0 month in the ARIKAYCE arm and 2.0 months in the comparator arm. Notably, no patients in this study developed a MAC isolate with resistance to ARIKAYCE and/or macrolide.

The discontinuation rate of ARIKAYCE or the placebo used in the comparator arm was 22.9% in the ARIKAYCE arm and 7.8% in the comparator arm. Study completion rates were 91.7% in the ARIKAYCE arm and 94.1% in the comparator arm. No new safety signals were observed in the ARIKAYCE arm, and the safety profile in general was as expected in both treatment arms. Treatment-emergent adverse events (TEAEs) were reported by 91.7% of patients in the ARIKAYCE arm and 80.4% of patients in the comparator arm.

The most common TEAEs were dysphonia (41.7% for the ARIKAYCE arm vs. 3.9% for the comparator arm), cough (27.1% vs. 7.8%), diarrhea (27.1% vs.

25.5%), and COVID-19 (12.5% vs. 9.8%). Of the treatment-emergent serious adverse events observed in the trial, none were determined to be related to ARIKAYCE and none were deemed related to COVID-19.

The ARISE and ENCORE clinical trial program is intended to fulfill the FDA's post-marketing requirement to allow for full approval of ARIKAYCE in the U.S. and to support a supplemental new drug application for the use of ARIKAYCE as a treatment for patients with a MAC lung infection. ARISE was a global, randomized, double-blind, placebo-controlled, Phase 3b study in adult patients with newly diagnosed or recurrent MAC lung disease who had not received antibiotics for their current infection that aimed to generate evidence demonstrating the domain specification, reliability, validity, and responsiveness of PRO-based scores. Patients were randomized 1:1 to receive ARIKAYCE plus background regimen or placebo plus background regimen once daily for six months.

Patients then discontinued all study treatments and remained in the trial for one month for the continued assessment of PRO endpoints. The study enrolled 99 patients. The ongoing ENCORE trial is a randomized, double-blind, placebo-controlled, Phase 3b study to evaluate the efficacy and safety of an ARIKAYCE-based regimen in patients with newly diagnosed or recurrent MAC lung disease who have not started antibiotics.

Patients are randomized 1:1 to receive ARIKAYCE plus background regimen or placebo plus background regimen once daily for 12 months. Patients will then discontinue all study treatments and remain in the trial for three months for the assessment of durability of culture conversion. The primary endpoint is change from Baseline to Month 13 in respiratory symptom score.

The key secondary endpoint is the proportion of patients achieving durable culture conversion at Month 15. ARIKAYCE is approved in the United States as ARIKAYCE® (amikacin liposome inhalation suspension), in Europe as ARIKAYCE® Liposomal 590 mg Nebuliser Dispersion, and in Japan as ARIKAYCE® inhalation 590 mg (amikacin sulfate inhalation drug product). Current international treatment guidelines recommend the use of ARIKAYCE for appropriate patients.

ARIKAYCE is a novel, inhaled, once-daily formulation of amikacin, an established antibiotic that was historically administered intravenously and associated with severe toxicity to hearing, balance, and kidney function. Insmed's proprietary PULMOVANCE® liposomal technology enables the delivery of amikacin directly to the lungs, where liposomal amikacin is taken up by lung macrophages where the infection resides, while limiting systemic exposure. ARIKAYCE is administered once daily using the Lamira® Nebulizer System manufactured by PARI Pharma GmbH (PARI).

ARIKAYCE is delivered by a novel inhalation device, the Lamira® Nebulizer System, developed by PARI. Lamira® is a quiet, portable nebulizer that enables efficient aerosolization of ARIKAYCE via a vibrating, perforated membrane. Based on PARI's 100-year history working with aerosols, PARI is dedicated to advancing inhalation therapies by developing innovative delivery platforms to improve patient care.