Austria’s Nabriva Therapeutics has finished enrolling patients for its first Phase 3 clinical trial evaluating lefamulin treatment against community-acquired bacterial pneumonia (CABP).
The most common type of pneumonia, CABP afflicts more than five million Americans annually, of which three million are diagnosed at an in-patient hospital or emergency department setting. They are then treated with intravenous (IV) and oral antibiotics.
Yet bacterial resistance to antibiotics is a major concern. Patients on ventilators — often used in intensive-care units — and those who live in long-term care facilities or go frequently to outpatient clinics are at higher risk of developing CABP.
“Bacterial resistance to commonly prescribed antibiotics for the treatment of CABP continues to rise globally, rendering those antibiotics less effective and increasing the need for new classes of therapies,” Elyse Seltzer, MD, chief medical officer of Nabriva, said in a press release.
For this reason, Nabriva is developing lefamulin, a novel semi-synthetic pleuromutilin that inhibits protein synthesis, in two international, randomized, double-blind Phase 3 clinical trials in patients with moderate to severe CABP. The studies are called Lefamulin Evaluation Against Pneumonia (LEAP) 1 and 2.
LEAP 1 (NCT02559310), which includes 550 patients with moderate to severe CABP, compares lefamulin to Avelox (moxifloxacin), a fluoroquinolone type of antibiotic that is commonly used to treat respiratory and urinary tract infections. LEAP 1 aims to evaluate the safety and efficacy of lefamulin (IV/oral) compared to Avelox (IV/oral), with or without Zyvox (linezolid), an antibody used in drug-resistant bacterial infections. Nabriva expects to publish data from LEAP 1 in late 2017.
LEAP 2 (NCT02813694) will compare the efficacy and safety of oral lefamulin to oral Avelox in people with moderate CABP. Nabriva aims to enroll 738 patients in LEAP 2. Patient enrollment should be finished in late 2017, with top-line data available in early 2018.
“As the potential first-in-class pleuromutilin available for systemic administration in humans, lefamulin could provide a monotherapy for patients with moderate to severe CABP, with targeted activity against the most common pathogens, including multi-drug resistant strains,” said Seltzer.
Nabriva believes lefamulin is the first antibiotic with a novel mechanism of action to reach the late stages of clinical development in more than a decade. Its likely use as a monotherapy to treat moderate to severe CABP is thanks to its targeted spectrum of activity, tolerability and resistance profiles, substantial drug concentration in the lungs, and the existence of both oral and IV formulations. In parallel, Nabriva is developing a formulation of lefamulin for pediatric use.