The U.S. Food and Drug Administration (FDA) gave Dublin-based Nabriva Therapeutics a thumbs-up for both its oral and intravenous formulations of Xenleta (lefamulin) to treat community-acquired bacterial pneumonia (CABP) in adults. It is the first IV and oral antibiotic with a new mechanism of action the agency has approved in almost twenty years.
“Today’s approval of Xenleta is a significant breakthrough in the collective fight against the growing threat of antimicrobial resistance and provides a desperately needed IV and oral empiric monotherapy treatment option for adults with CABP,” stated Ted Schroeder, Nabriva’s chief executive officer. “We are especially proud of this approval because Xenleta was discovered in our labs over a decade ago and the entire development program was designed and executed by our dedicated and passionate team.”
Xenleta is a first-in-class semi-synthetic pleuromutilin antibiotic for systemic administration. It inhibits the synthesis of a bacterial protein needed for the bacteria to grow. It has been shown to have a targeted range of activity, resistance profile, and can concentrate in lung tissue and fluid, the target tissues for pneumonia.
Community-acquired refers to developing a disease outside of a hospital. According to the U.S. Centers for Disease Control and Prevention (CDC), about one million people are hospitalized in the U.S. with community-acquired pneumonia each year and about 50,000 people die from it.
The most common cause of bacterial pneumonia in the U.S. is Streptococcus pneumoniae. However, according to recent data from the SENTRY Antimicrobial Surveillance Program, about 30 to 60% of S. pneumoniae in the U.S., depending on region, are resistant to macrolides. Macrolides and fluoroquinolones are common treatments for CABP, but fluoroquinolones have boxed warnings for several safety concerns.
Both applications were granted priority review, as well as Fast Track designation and Qualified Infectious Disease Product (QIDP) designation.
The two New Drug Applications (NDAs) were built on two pivotal, Phase III clinical trials, LEAP 1 and LEAP 2, that compared the two formulations of lefamulin to moxifloxacin in adults with CABP. The drug has also been approved for review by the European Medicines Agency (EMA).
The most common adverse events in the Xenleta cohorts included diarrhea, nausea, injection site reactions, elevated liver enzymes and vomiting. It can also cause changes on an ECG reading, prolonged QT interval. As a result, the antibiotic is contraindicated in patients with prolonged QT interval, specific irregular heart rhythms, and patients receiving drugs for either of those.
The company believes Xenleta will be available through major U.S. specialty distributors by mid-September 2019. Its wholesale acquisition (WAC) price will be $205 per IV patient treatment day and $275 per oral patient treatment day.
“Emergency departments across the country treat hundreds of thousands of patients with CABP each year,” said Philip Giordano, vice chairman of Emergency Medicine at the Orlando Regional Medical Center. “Many of these patients, especially elderly patients with comorbidities, are admitted solely because of the lack of an effective and well-tolerated oral treatment option. With a new oral antibiotic option that has been shown to be as effective as a respiratory fluoroquinolone, possessing a favorable side effect profile, we can consider sending more patients home directly from the emergency department and avoid costly hospitalizations, which is good for both patient care and the health system.”