Nontuberculous mycobacterial pulmonary disease and the potential role of SPR720

ABSTRACT

Introduction

Nontuberculous mycobacteria infect patients who have structural lung disease or those who are immunocompromised. Nontuberculous mycobacterial pulmonary disease (NTM-PD) is increasing in prevalence. Treatment guidelines for Mycobacterium avium complex (MAC) pulmonary disease involve a three-drug regimen with azithromycin, ethambutol, and rifampin, and those of Mycobacterium abscessus complex (MAB) pulmonary disease involve a combination of three or more antimicrobials including macrolides, amikacin, and a β-lactam or imipenem. However, these regimens are poorly tolerated and generally ineffective.

Areas covered

SPR720 is a novel therapeutic agent that has demonstrated activity against a range of NTM species, including MAC and MAB. Encouraging in vitro and pre-clinical data demonstrate that SPR720 is active both alone and in combination with standard-of-care agents, with no evidence of cross-resistance to such agents. It is generally well tolerated with mainly gastrointestinal and headache adverse events of mild or moderate severity.

Expert opinion

Management of NTM-PD is challenging for many reasons including length of therapy, poor efficacy, drug intolerance, recurrence, and resistance development. The current antimicrobial management options for NTM-PD are limited in number and there exists a large unmet need for new treatments. SPR720 has encouraging data that warrant further study in the context of a multidrug regimen.

KEYWORDS:

• Nontuberculous mycobacteria
• Mycobacterium avium complex
• pulmonary disease
• guidelines
• therapy
• SPR720

Article highlights

• Nontuberculous mycobacteria, including MAC and MAB, can cause pulmonary infections that are increasing in prevalence.

• Underlying lung disease such as bronchiectasis or chronic obstructive pulmonary disease, immunosuppression, and older age are the biggest risk factors.

• Management of NTM-PD is clinically challenging due to the long duration of complex multidrug antibiotic regimens, poor efficacy, recurrence, and resistance development.

• Current therapies are poorly tolerated, which often leads to early treatment discontinuation.

• SPR720 is a novel oral aminobenzimidazole that inhibits in mycobacteria the ATPase activity of DNA gyrase B.

• This agent has demonstrated activity against MAC and MAB both alone and in combination with standard-of-care agents in vitro and in pre-clinical models.

• SPR720 was well tolerated in a phase 1 randomized, double-blind, placebo-controlled trial with mainly mild or moderately severe gastrointestinal or headache adverse events.

• SPR720 is currently in phase 2 clinical studies.

Declaration of interest

KL Winthrop has received research support from AN2 Therapeutics, Insmed, Paratek Pharmaceuticals, RedHill Biopharma, Renovion, and Spero Therapeutics, and is a consultant for AN2 Therapeutics, Insmed, Paratek Pharmaceuticals, RedHill Biopharma, Renovion, and Spero Therapeutics. P Flume has received grant support from AbbVie, AN2 Therapeutics, Armata Pharmaceuticals, AstraZeneca, Cystic Fibrosis Foundation Therapeutics, Insmed, Janssen Pharmaceuticals, National Institutes of Health, Novovax, RedHill Biopharma, Sound Pharmaceuticals, Spero Therapeutics, Synchrony Bio, and Vertex Pharmaceuticals; and is a consultant for AN2 Therapeutics, Chiesi Farmaceutici, Eloxx Pharmaceuticals, Insmed, Ionis Pharmaceuticals, Janssen Research & Development, McKesson, Sionna Therapeutics, Spero Therapeutics, and Vertex Pharmaceuticals. KA Hamed is an employee of Spero Therapeutics. 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 material discussed in the manuscript apart from those disclosed.

Reviewer disclosures

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

Additional information

Funding

This paper was not funded.