FDA OKs 'New-Gen' Antibiotic for Pneumonia, Skin Infections

The FDA approved omadacycline (Nuzyra) Wednesday for the treatment of community-acquired bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections (ABSSSI), Paratek Pharmaceuticals announced.

Omadacycline is a semisynthetic derivative tetracycline antibiotic, specifically designed to overcome tetracycline resistance and proven to be effective across Gram-positive, Gram-negative, and other drug-resistant strains.

It has been nearly 20 years since the FDA approved a once-daily IV and oral antibiotic for the treatment of both CABP and ABSSSI, according to the release. The approval, which follows an FDA advisory committee recommendation in August, comes after more than two dozen clinical studies in this setting. The drug is expected to be available in the first quarter of 2019.

"Omadacycline is the first in its class, what we describe as a new-generation tetracycline," Evan Tzanis, chief development officer of Paratek Pharmaceuticals, told MedPage Today ahead of the approval. "However, the modifications that we've made to the structure of the classic tetracycline are such that omadacycline has overcome the most common resistant pathways that have developed in tetracycline."

The results of two noninferiority trials, OASIS-1 and OASIS-2, demonstrated the efficacy of omadacycline in treating ABSSSI. In OASIS-1, patients were administered omadacycline intravenously. The drug demonstrated an 84.8% clinical success rate, defined as at least a 20% reduction in their lesion, compared to 85.5% of those who received linezolid.

In OASIS-2, patients were administered the omadacycline orally and exhibited an 87.5% clinical success rate, compared to 82.5% in those who received linezolid. The two trials resulted in 8 patient deaths in the omadacycline group. Patients had bacterial pathogens identified at baseline in four of these cases and more than one baseline organism in three cases.

And omadacycline demonstrated noninferiority to moxifloxacin in the phase III OPTIC trial of 774 CABP patients, with each arm reporting comparable rates of early and post-therapy clinical response across Pneumonia Outcomes Research Team (PORT) class II-IV groups -- in the 75% to 86% range for early response depending on class, and 80% to 90% for post-therapy response.

In the U.S., CABP and ABSSSI cause millions of illnesses each year. And as antibiotic resistance poses an increasingly significant challenge in treating bacterial infection, effective therapies are in high demand. Keith Kaye, MD, MPH, of the Division of Infectious Diseases at the University of Michigan, said in the company's press release that developing antibiotics to treat both CABP and ABSSSI is particularly important as antibiotic resistance continues to grow and current treatments may become less effective.

"This reality makes it increasingly challenging to provide safe and effective treatments to patients," Kaye said. "There continues to be a need for novel antibiotics with both IV and oral formulations, such as Nuzyra, to help physicians stay ahead of the evolving resistance landscape."

Known as an aminomethylcycline, omadacycline works by binding to the 30S subunit of the bacterial ribosome and blocks protein synthesis. Much like other other tetracyclines, it then inhibits the binding of aminoacyl-tRNA.

Common adverse reactions associated with omadacycline (incidence ≥2%) in the OPTIC and OASIS trials included nausea, vomiting, infusion site reactions, increased alanine or aspartate aminotransferase, increased gamma-glutamyl transferase, hypertension, headache, diarrhea, insomnia, and constipation.

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