Nabriva Therapeutics releases lefamulin topline results

Andrew Shorr

Nabriva Therapeutics announced positive topline results from a second phase 3 clinical trial of lefamulin for the treatment of community-acquired bacterial pneumonia, showing that the investigational antibiotic met all FDA and European Medicines Agency primary endpoints.

“We’ve been limited in our treatment choices for community-acquire bacterial pneumonia for some time,” Andrew Shorr, MD, MPH, MBA, section head of pulmonary and critical care medicine at MedStar Washington Hospital Center, told Infectious Disease News. “I think the data show that hopefully soon we’ll have a new tool in the tool kit to deal with the very serious and burdensome illness..”

Lefamulin Evaluation Against Pneumonia, or LEAP 2, is a randomized, double-blind, double-dummy clinical trial that evaluated the safety and efficacy of 600 mg of oral lefamulin twice daily for 5 days compared with 400 mg of moxifloxacin.

As previously reported, the company conducted its first phase 3 trial for the new community-acquired bacterial pneumonia (CABP) treatment in September 2017, which found that IV to oral lefamulin was noninferior when compared with IV to oral moxifloxacin, with or without linezolid.

“We are especially pleased with the high response rates for lefamulin in LEAP 1 and LEAP 2 and plan to file a new drug application with the FDA in the fourth quarter of 2018,” Colin Broom, MD, Nabriva Therapeutics’ CEO, said in the release.

Of the 738 patients with CABP enrolled in LEAP 2, 370 received lefamulin and 368 received moxifloxacin.

Nabriva reported that rates of early clinical response (ECR) — measured 72 to 120 hours following initiation of therapy — were 90.8% for both treatment courses (treatment difference= 0.1 [95% CI, –4.4 to 4.5]). This fell within the 10% noninferiority margin established by the FDA.

The drug also met the primary endpoint for noninferiority (within 10%) of the European Medicines Agency (EMA) regarding an investigator assessment of clinical response (IACR) rates 5 to 10 days following the completion of therapy in the modified intent-to-treat (mITT) and clinically evaluable at test-of-cure (CE-TOC) patient populations. IACR rates for the mITT population were 87.5% for lefamulin and 89.1% for moxifloxacin (treatment difference, –1.6 [95% CI, –6.3 to 3.1]), and 89.7% for lefamulin and 93.6% for moxifloxacin (treatment difference = –3.9 [95% CI, –8.2 to 0.5]) in the CE-TOC population.

According to the release, 49.5% of patients receiving lefamulin had a Pneumonia Outcomes Research Team (PORT) class of 2, 39.2% had a PORT class of 3 and 10.8% had a PORT class of 4. Among those who received moxifloxacin, 51.4% had a PORT class of 2, 36.1% had a PORT class of 3 and 11.4% had a PORT class of 4.

Treatment-emergent adverse event rates for lefamulin was 32.6% and 25% for moxifloxacin. Furthermore, 4.6% of patients treated with lefamulin and 4.9% of patients treated with moxifloxacin experienced serious adverse events.

“Overuse of cephalosporins or quinolones have any number of deleterious effects on resistance and other outcomes that are important to hospitals and patients. So, having a new tool in the tool kit, I think, is crucial to improving the ability for us to take care of these patients,” Shorr said in the interview. “Now, potentially having new alternatives, it means we have to re-evaluate how to risk stratify patients, identify patients who are best candidates for certain kinds of therapy and figure out how these therapies we use are going to transition patients from the hospital to the community and do it in a way that’s successful.” – by Marley Ghizzone

Disclosures: Shorr is a consultant for Nabriva Therapeutics and Paratek Pharmaceuticals. Bloom works for Nabriva Therapeutics.