The First Oral Antibiotic Designed to Treat Non-tuberculous Mycobacterial Infections, a rare orphan disease.

Non-tuberculous Mycobacterium (NTM) is a growing global health concern and major unmet medical need because of the lack of new medications being developed to combat these bacteria.

NTM are ubiquitous environmental pathogens that can cause progressive lung damage and respiratory failure, particularly in patients with compromised immune systems or underlying pulmonary disorders.  Although rare, the incidence of pulmonary NTM infections is increasing worldwide. It is estimated that approximately 130,000 patients suffer from NTM in the U.S. and Europe, a figure that is growing at a rate of 8% annually. The elderly and people with compromised immune or lung function are at greatest risk, as are patients with bronchiectasis for whom it is estimated that up to 50% may also have active NTM lung infection.

Treatment of pulmonary NTM infections requires prolonged therapy (continuing for approximately 12 to 24 months) with a combination of mostly unapproved drugs and is frequently complicated by tolerability and/or toxicity issues. Additionally, there are currently no oral antibiotics specifically approved for use to treat pulmonary NTM infections.

The most common treatment for NTM is combination therapy with drugs traditionally used for tuberculosis (TB) which have limited efficacy and high toxicity. NTM is also associated with high healthcare costs and high mortality. In 2014, the annual cost in the U.S. alone was estimated at $1.7 billion.

Spero Therapeutics is currently developing SPR720, a novel oral agent to treat NTM.

SPR720 represents a novel class of antibacterial agents that target enzymes essential for bacterial DNA replication. Pre-clinical in vitro and in vivo studies have demonstrated potency for SPR720 against Mycobacterium tuberculosis (TB) and a range of bacteria that cause NTM infections, including Mycobacterium avium complex and Mycobacterium abscessus. 

SPR720 is currently in a Phase 1 clinical trial.  The purpose of this clinical trial is to evaluate SPR720 in a double-blind, placebo-controlled study in healthy subjects consisting of single ascending dose and multiple ascending dose cohorts. SPR720 is an orally administered antimicrobial agent being developed for the treatment of nontuberculous mycobacterial (NTM) infections.

The advancement of SPR720 into the Phase 1 clinical assessment was based on SPR720’s favorable profile exhibited in a suite of pre-clinical in vitro and in vivosafety, toxicology and ADME (absorption, distribution, metabolism and excretion) studies, as well as its demonstration of potent in vitro and in vivo activity versus multiple, clinically important species of NTM, including Mycobacterium avium complex and Mycobacterium abscessus. The collective pre-clinical data to date suggest that SPR720 has an acceptable safety profile, encouraging target pathogen efficacy, drug distribution to key sites of infection, such as the lung, and a wide therapeutic margin.