Management and Resolution of Hypersensitivity Pneumonitis‑Related Events in Japanese Patients Treated with Amikacin Liposome Inhalation Suspension in the CONVERT and INS‑312 Clinical Trials

Sep 30, 2026

Phase 3 CONVERT evaluated amikacin liposome inhalation suspension (ALIS) plus guideline-based therapy (GBT) versus GBT alone in refractory Mycobacterium avium complex pulmonary disease (MAC-PD), with culture conversion benefits but an increased rate of hypersensitivity pneumonitis. In Japanese patients, hypersensitivity pneumonitis related to ALIS occurred more often (3.1%, n=7 vs 0.9%, n=1), and all four Japanese cases presented half after ALIS initiation. Serious cases were linked to ALIS, and after ALIS discontinuation and medical intervention, all patients recovered. Imaging and serum KL-6 supported assessment at symptom onset (both KL-6 >600 U/mL). Radiographic and KL-6 changes may inform management strategies, though further research is needed.

LanguageEnglish

CategoryHealthcare

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Pages15

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Introduction

Infect Dis Ther (2026) 15:365–379 [https://doi.org/10.1007/s40121-025-01247-7](https://doi.org/10.1007/s40121-025-01247-7) CASE SERIES Management and Resolution of Hypersensitivity Pneumonitis‑Related Events in Japanese Patients Treated with Amikacin Liposome Inhalation Suspension in the CONVERT and INS‑312 Clinical Trials Yoshitaka Yamazaki · Taku Nakagawa · Zhanna Jumadilova · Dayton Yuen · Raul Villa · Naoki Hasegawa Received: July 29, 2025 / Accepted: October 6, 2025 / Published online: November 4, 2025 © The Author(s) 2025 ABSTRACT In the phase 3 CONVERT trial, amikacin liposome inhalation suspension (ALIS) plus guideline-based therapy (GBT) achieved greater culture conversion than GBT alone in the treatment of refractory Mycobacterium avium complex pulmonary disease (MAC-PD) . In the original analysis of safety data in CONVERT, the rate of hypersensitivity pneumonitis, a prespecified group of adverse events of special interest, was higher in Y. Yamazaki Division of Infectious Diseases, Shinshu Medical Center, 1332 Suzaka, Nagano 382-8577, Japan T. Nakagawa Department of Respiratory Medicine, NHO Higashinagoya National Hospital, 5-101 Umemorizaka, Meito-ku, Nagoya-shi, Aichi 465-8620, Japan Z. Jumadilova · D. Yuen Clinical Development, Insmed Incorporated, 700 US Highway 202/206, Bridgewater, NJ 08807, USA R. Villa Drug Safety and Pharmacovigilance, Insmed Incorporated, 700 US Highway 202/206, Bridgewater, NJ 08807, USA N. Hasegawa (*) Center for Clinical Infectious Diseases, Keio University Hospital, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan [e-mail: n-hasegawa@keio.jp](e-mail: n-hasegawa@keio.jp) patients receiving ALIS plus GBT (3.1%; n = 7) versus GBT alone (0.9%; n = 1), with half of the cases reported in Japanese patients. We present a summary of serious adverse events of hypersensitivity pneumonitis that investigators deemed related to ALIS treatment in Japanese patients enrolled in CONVERT (n = 3) and its extension study (INS-312; n = 1) . Patients were women older than 65 years diagnosed with pneumonitis (n = 3) or interstitial lung disease (n = 1) after initiation of ALIS (range 3–189 days) . Following ALIS discontinuation and medical intervention, all four patients recovered from pneumonitis. Additional investigator-collected imaging and serum Krebs von den Lungen 6 (KL-6) data were available for two of these patients, permitting assessment of KL-6 and the potential diagnostic role of radiographic findings. At the time of diagnosis, one patient had ground-glass opacity, and the other patient had consolidation in the right lower lobe of the lung; both patients had serum KL-6 levels > 600 U/mL. Changes inchest radiography and KL-6 levels at the onset of respiratory symptoms during ALIS treatment suggest that these assessments may help guide management strategies for potential hypersensitivity pneumonitis in patients taking ALIS. Clinical Trial Registration: NCT02344004 (CONVERT) and NCT02628600 (INS-312) . Keywords: Amikacin liposome inhalation suspension; Hypersensitivity pneumonitis; Krebs von den Lungen 6; Mycobacterium avium complex pulmonary disease; Nontuberculous mycobacterial pulmonary disease; Lung disease; Radiographic finding Key Summary Points International and Japanese guidelines recommend the use of amikacin liposome inhalation suspension (ALIS) as an add-on therapy in patients with treatment-refractory Mycobacterium avium complex pulmonary disease (MAC-PD) . The use of ALIS was associated with an increased rate of hypersensitivity pneumonitis, a prespecified group of adverse events of special interest, in the CONVERT trial and its open-label safety extension. This case series presents a summary of serious adverse events of hypersensitivity pneumonitis that investigators deemed related to ALIS treatment in Japanese patients enrolled in CONVERT and its extension study. Following medical intervention and ALIS discontinuation, all patients

FAQs

What was the main finding regarding hypersensitivity pneumonitis in the CONVERT trial?

In the CONVERT trial, adding ALIS to guideline-based therapy increased the rate of hypersensitivity pneumonitis compared with GBT alone, with cases reported in both CONVERT and its open-label safety extension.

How were the hypersensitivity pneumonitis cases in Japanese patients characterized?

Investigators reported serious hypersensitivity pneumonitis cases in Japanese patients enrolled in CONVERT and INS-312, with patients older than 65 years and diagnosed with pneumonitis or interstitial lung disease after ALIS initiation.

What happened after ALIS discontinuation, and what biomarkers were used?

After ALIS discontinuation and medical intervention, all four patients recovered from pneumonitis. Additional imaging and serum KL-6 data were available for some patients, and KL-6 levels exceeded 600 U/mL at diagnosis.

Sep 30, 2026

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