FDA OKs First-in-Class Antibiotic Lefamulin (Xenleta) for CABP

Megan Brooks

August 19, 2019

The US Food and Drug Administration (FDA) has approved lefamulin (Xenleta, Nabriva Theraputics), a new oral and intravenous (IV) antibiotic for the treatment of adults with community-acquired bacterial pneumonia (CABP).

Lefamulin is a first-in-class semisynthetic pleuromutilin antibiotic indicated for CABP caused by the following susceptible microorganisms: Streptococcus pneumoniae, Staphylococcus aureus (methicillin-susceptible isolates), Haemophilus influenzae, Legionella pneumophila, Mycoplasma pneumoniae, and Chlamydophila pneumoniae.

Lefamulin's mechanism of action is different from that of other approved antibiotics, "resulting in a low propensity for the development of resistance, as well as a lack of cross-resistance with the beta-lactam, fluoroquinolone, glycopeptide, macrolide, and tetracycline antibiotic classes," Ted Schroeder, chief executive officer of Nabriva Therapeutics, said in a news release.

"Xenleta has a targeted in vitro spectrum of activity against the most common causative Gram-positive, Gram-negative and atypical pathogens associated with CABP, which aligns with the principles of antimicrobial stewardship," said Schroeder.

The Centers for Disease Control and Prevention estimates that about 1 million people are hospitalized with community-acquired pneumonia and that 50,000 people die from the disease each year in the United States.

The safety and efficacy of lefamulin were evaluated in two studies involving close to 1300 patients with CABP. In those studies, lefamulin was compared to moxifloxacin, with or without linezolid.

The studies showed that for patients treated with lefamulin, rates of clinical success were similar to those of patients treated with moxifloxacin, with or without linezolid.

"This new drug provides another option for the treatment of patients with community-acquired bacterial pneumonia, a serious disease," Ed Cox, MD, director of the FDA's Office of Antimicrobial Products, said in an FDA news release.

"For managing this serious disease, it is important for physicians and patients to have treatment options. This approval reinforces our ongoing commitment to address treatment of infectious diseases by facilitating the development of new antibiotics," said Cox.

The most common adverse reactions reported for patients taking lefamulin included diarrhea, nausea, reactions at the injection site, elevations in liver enzyme levels, and vomiting. Lefamulin may cause prolongation of the QT interval and should be avoided in these patients and in patients with arrhythmias, the FDA said.

Lefamulin should also not be used in patients with known hypersensitivity to lefamulin or any other members of the pleuromutilin antibiotic class or to any of the components of lefamullin.

"Based on findings of fetal harm in animal studies, pregnant women and women who could become pregnant should be advised of the potential risks of Xenleta to a fetus. Women who could become pregnant should be advised to use effective contraception during treatment with Xenleta and for two days after the final dose," the FDA advised.

Lefamulin will be available for oral (600 mg every 12 hours) and IV (150 mg every 12 hours) administration with a short 5- to 7-day course of therapy.

Patients can initially be treated with either IV or oral therapy, potentially avoiding a hospital stay, or patients can transition from IV to oral therapy, which may expedite discharge from the hospital, the company said.

The company expects lefamulin to be available through major US specialty distributors in mid-September 2019 and predicts a wholesale acquisition price of $205 per IV patient treatment day and $275 per oral patient treatment day.

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