Omadacycline, a novel antibiotic in the tetracycline class, was non-inferior to standard of care for both community-acquired bacterial pneumonia and acute bacterial skin and skin-structure infections, two randomized trials found.
There was no significant difference in early clinical response among patients with community-acquired bacterial pneumonia randomized to omadacycline and those randomized to antibiotic moxifloxacin, reported Roman Stets, MD, of City Clinical Hospital in the Ukraine, and colleagues.
Likewise, there was no difference in early clinical response in patients with acute bacterial skin and skin-structure infections who received omadacycline versus those treated with antibiotic linezolid, reported William O'Riordan, MD, of eStudy Site, which operates three clinical research sites, including two in San Diego, and colleagues.
These studies were submitted by manufacturer Paratek Pharmaceuticals to the FDA as part of its marketing application for omadacycline, which was approved last October. They were published with peer review Wednesday in the New England Journal of Medicine.
An accompanying editorial by Henry F. Chambers, MD, of the University of California, San Francisco, characterized the two trials as having "checked all the boxes required of a high-quality, interventional clinical trial." He added that the therapy could offer an advantage for acute bacterial and skin-structure infections.
"The oral formulation of omadacycline may offer an advantage in certain circumstances -- for example, it could be given instead of linezolid as treatment for the occasional patient receiving monoamine oxidase inhibitor or antiserotonergic antidepressant therapy," Chambers wrote.
More importantly, he speculated on its role for treating infections caused by multi-drug resistant pathogens, which he characterized as "a question desperately in need of an answer."
Chambers said omadacycline "does not have cross-resistance with beta-lactam antibiotics, aminoglycosides, polymyxins, and fluoroquinolones and is active against organisms expressing tetracycline efflux and ribosomal protection genes," adding that, "it is many times more active than doxycycline and minocycline against Enterobacteriaceae and Acinetobacter baumannii."
Despite characterizing omadacycline as "the latest candidate with at least some promise for the treatment of infections caused by carbapenem-resistant Enterobacteriaceae and species of acinetobacter," Chambers said that well-designed clinical trials of omadacycline will be needed to determine its value in the treatment of multiple-drug-resistant gram-negative pathogens.
The study by Stet and colleagues randomized 386 patients with community-acquired bacterial pneumonia to omadacycline and 388 to moxifloxacin in an intention-to-treat population. Patients randomized to receive omadacycline had a 81.1% rate of response compared with 82.7% of patients who received moxifloxacin, with the authors using a non-inferiority margin of 10%. Early clinical response was defined as survival with improvement in at least two of four symptoms (cough, sputum production, pleuritic chest pain, and dyspnea) and no worsening of symptoms at 72 to 120 hours without the need for antibacterial therapy.
Similarly, the treatment also met a secondary endpoint of rates of investigator-assessed clinical response 5 to 10 days after the last dose, defined as resolution or improvement in signs or symptoms, so that further antibacterial therapy was unnecessary (87.6% for omadacycline vs 85.1% for moxifloxacin).
In the second study by O'Riordan and colleagues, 316 patients with acute bacterial skin and skin-structure infections were randomized to receive omadacycline, while 311 received in a modified intention-to-treat population. They found that omadacycline was non-inferior to linezolid (rate of response 84.8% and 85.5%, respectively), with early clinical response at 48 to 72 hours defined as survival with a reduction in lesion size of at least 20% without rescue antibacterial therapy.
Secondary endpoints of rates of investigator-assessed clinical response 7 to 14 days after the last dose found a rate of response of 86.1% in the omadacycline group and 83.6% in the linezolid group. The authors also noted that efficacy of omadacycline was "similar" for both methicillin-susceptible and methicillin-resistant Staphylococcus aureus infections.
Rates of adverse events in both trials were similar, and the most frequent was gastrointestinal adverse events, the authors said.
Both studies were supported by Paratek Pharmaceuticals.
Stets disclosed support from Paratek Pharmaceuticals.
O'Riordan disclosed support from Paratek, Motif, Basilea, The Medicines Company, GlaxoSmithKline, Debiopharm, and Cellceutix. Co-authors disclosed support from Paratek Pharmaceuticals, Achaogen, IterumTx, Nabriva, ContraFect, Wockhardt, UTILITY, Zavante, Tetraphase, Theravance, Cubist, Cempra, Spero Therapeutics, InClin, and MicuRx.
Chambers disclosed support from Allergan.
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