FDA Advisory Committee Recommends Approval of Omadacycline For Treatment of CABP & ABSSSI

The US Food and Drug Administration (FDA)’s Antimicrobial Drugs Advisory Committee has voted to recommend the approval of Paratek Pharmaceutical’s omadacycline for the treatment of community-acquired bacterial pneumonia (CABP) and acute bacterial skin and skin structure infections (ABSSSI).

Omadacycline is a once-daily intravenous (IV) and oral, broad-spectrum antibiotic. The drug is a modernized tetracycline that is being developed to overcome tetracycline resistance and has shown activity in gram-positive, gram-negative, anaerobes, and atypical bacteria.

The vote was 17 to 1 in favor of approval of omadacycline for treatment of ABSSSI and 14 to 4 for the treatment of CABP.

“This drug offers a valuable treatment alternative for pneumonia and for skin infections,” said Keith Kaye, MD, MPH, director of clinical research, division of infectious diseases, University of Michigan, Contagion® Editorial Advisory Board Member, and a presenter at the Advisory Committee, told Contagion®. “It is available in both intravenous and oral formulations, has activity against resistant pathogens including methicillin-resistant Staphylococcus aureus and resistant pneumococcus and also has a very good safety profile with a low risk for Clostridium difficile.

The Advisory Committee based their decision off of data from the omadacycline global development program which included 3 phase 3 trials that assessed the safety and efficacy of omadacycline. The results of the trials showed that the drug met all required primary endpoints set by the FDA and the European Medicines Agency (EMA). Furthermore, the drug was found to be generally safe and well-tolerated.

Between the 3 phase 3 trials, 2150 participants were exposed to omadacycline. According to Advisory Committee documents, efficacy for the treatment of ABSSSI was demonstrated in 2 clinical trials where omadacycline was observed to be noninferior to linezolid. Efficacy for the treatment of CABP was observed in a clinical trial as omadacycline was found to be noninferior to moxifloxacin. However, the committee reported concerns over the imbalance in mortality observed in the CABP trial, which reported 12 deaths, 8 of which occurred in participants who received omadacycline.

According to the FDA Advisory Committee’s meeting materials, “An etiology for the imbalance could not be determined from the available current data. Although the rate of mortality in the omadacycline group appears to be similar to the 30-day mortality observed in recently conducted CABP trials, this mortality imbalance in a randomized controlled trial is noteworthy.”

Dr Kaye addressed the FDA’s concerns saying, “This was a subgroup analysis and was not statistically significant—this could have very possibly been a chance finding, unrelated to [the] study drug.” He added, “Several of the deaths seemed completely unrelated to antibiotic treatment or infection. However, if approved, additional studies to evaluate mortality are warranted.”

Previous to this meeting, the FDA has granted omadacycline Qualified Infectious Disease Product designation and Fast Track status. Additionally, following the FDA acceptance of the New Drug Application (NDA) for CABP and ABSSSI, omadacycline has also been granted priority review. The Prescription Drug Fee User Act (PDUFA) date for both NDAs is expected in early October.

The drug is being researched by the US Department of Defense in activity against pathogenic agents which cause particularly concerning infectious diseases.

Paratek Pharmaceuticals is also preparing a market authorization application for omadacycline in the European Union.