Amikacin liposome inhalation suspension as a treatment for patients with refractory mycobacterium avium complex lung infection

ABSTRACT

Introduction: Amikacin liposome inhalation suspension (ALIS) contains amikacin sulfate, an aminoglycoside antibacterial drug. It has been approved in the US as a combined antibiotic treatment for refractory MAC lung disease patients. ALIS, as an inhaled antibiotic, can deliver amikacin to the infected site effectively and reduce systemic toxicity.

Areas covered: This article gives a summated review of the pharmacodynamics, pharmacokinetics, therapeutic efficacy, post-marketing surveillance, and regulatory affairs of ALIS as an add-on therapy for MAC lung disease in adults by analyzing data from preclinical studies, clinical trials and original studies. We systematically searched Medline/PubMed through October 2020.

Expert opinion: Studies demonstrate that ALIS as an add-on treatment significantly improve the rate of sputum culture conversion in MAC lung disease patients compare to guideline-recommended therapy only. The ALIS treatment showed a similar risk of serious adverse events and a low chance of renal adverse events. However, ALIS was associated with more respiratory adverse events than guideline-recommended therapy only. There was not sufficient data to conclude that ALIS treatment can improve clinical outcomes; however, with the significant improvement in the microbiology outcome in MAC lung disease patients, ALIS showed its potential use as an adjunct treatment for treating MAC lung disease.

KEYWORDS:

• Amikacin
• mac lung disease
• antibiotic treatment
• sputum culture conversion
• respiratory adverse event

Declaration of interest

A. Hill has given expert advice to INSMED and involved in the preparation of reference 46, a Phase III study investigating ALIS treatment in MAC lung disease. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Article highlights

• Current guideline-based treatment for MAC lung disease is associated with poor clinical outcomes.

• The use of ALIS can increase intracellular amikacin delivery. ALIS significantly enhance amikacin uptake into macrophages compared to free amikacin, thus lead to more targeted antibacterial activity and less systemic toxicity from amikacin.

• In Phase II and III clinical studies, ALIS significantly improved patients’ mycobacterial culture conversion rate compares to guideline-based treatment.

• In clinical studies to date, ALIS has a significant side effect profile, but some symptoms can be mitigated with the addition of a short-acting beta 2 agonist pre and post ALIS if needed.

Additional information

Funding

This paper was not funded.