Omadacycline Monotherapy in Nontuberculous Mycobacterial Pulmonary Disease Caused by Mycobacterium abscessus: Results From a Phase 2, Double-blind, Randomized, Placebo-controlled Study.

Abstract

Omadacycline is an FDA-approved oral and intravenous treatment for adults with community-acquired bacterial pneumonia and acute bacterial skin and skin structure infection that demonstrates potent in vitro activity and in vivo efficacy versus Mycobacterium abscessus. A randomized, double-blind, placebo-controlled, multicenter phase 2 study of omadacycline monotherapy was conducted in adults with nontuberculous mycobacterial pulmonary disease (NTM-PD) caused by M. abscessus. Eligible patients meeting the diagnostic criteria for NTM-PD were randomized 1.5:1 to receive omadacycline 300 mg orally once daily or placebo for 84 days. Randomization was stratified by prior antibiotic treatment for M. abscessus (yes/no). Sixty-six patients were randomized (41 omadacycline, 25 placebo). At baseline, cough, fatigue, mucus production, shortness of breath, and throat clearing were the most bothersome and common symptoms (68.2%-95.4% of patients). For the primary endpoint, 34.1% and 20.0% of omadacycline and placebo patients, respectively, were responders by definition 1 (improvement in symptom severity at day 84 for at least half of baseline symptoms) and 34.1% and 12.0%, respectively, were responders by definition 2 (definition 1 plus no deterioration in severity of any baseline symptom). Key secondary and exploratory clinical and microbiological endpoints also favored omadacycline compared with placebo. Four (9.8%) patients discontinued omadacycline therapy due to a treatment-emergent adverse event (TEAE). The most frequent omadacycline-related TEAEs were gastrointestinal, particularly nausea. Results consistently favored omadacycline monotherapy over placebo across several endpoints in NTM-PD caused by M. abscessus. Omadacycline was well tolerated; nausea was the most frequent TEAE. Further investigations are warranted.