- Shares in Nabriva Therapeutics plc nearly doubled in value early Monday morning after news the Irish biopharma's antibiotic succeeded in the first of two Phase 3 studies evaluating the drug for treatment of a common type of bacterial pneumonia.
- In a 551-patient trial, Nabriva's drug lefamulin met its goal of demonstrating non-inferiority to standard therapy of moxifloxacin with or without linezolid in patients with community-acquired bacterial pneumonia (CABP).
- No new anti-infective has been developed for CABP in more than 15 years, despite it being a leading cause of infectious death in the U.S. — a state of affairs the Nabriva hopes to change with lefamulin.
Pharma investment into anti-infectives has stagnated even as the threat from antibiotic-resistant bugs continues to grow.
Nabriva, which came into existence as a spin-out from Swiss pharma Novartis AG's Sandoz unit, hopes to capitalize on that market need. As company CEO Colin Broom put it in a recent interview, Nabriva is a "consequence of big pharma getting out of the business [of anti-infectives]."
Lefamulin is the company's lead candidate and a potentially first-in-class pleuromutilin antibiotic for treatment of CABP.
It wouldn't be the first pleuromutilin antibiotic approved, however. That honor belongs to GlaxoSmithKline's retapamulin, which the Food and Drug Administration OK'd for topical use against staphylococcus aureus and streptococcus pyogenes.
Nabriva's LEAP 1 study was only designed to assess whether lefamulin's safety and efficacy matched the bar set by the current standard of care. Nabriva, though, believes lefamulin's attributes could make it a potent new tool to fight CABP.
"Due to lefamulin’s flexible dosing and targeted spectrum of activity against the pathogens most commonly associated with CABP, including multidrug-resistant strains, we believe that lefamulin is well suited to be a first-line empiric monotherapy," Broom said in a Monday statement.
Bacterial resistance to existing therapy, as well as a continued high mortality rate in CABP, has intensified the need for novel antibiotics.
In LEAP 1, treatment with lefamulin resulted in an early clinical response rate of 87.3%, comparable to the 90.2% rate seen with moxifloxacin with or without linezolid.
Similar adverse events were seen in the lefamulin and control arms of the study, but lefamulin showed a superior gastrointestinal safety profile than moxifloxacin. Elevations in liver transaminases were slightly more common with lefamulin, however, and one more patient died in the treatment group than did in the control group.
Nabriva designed lefamulin to be given both intravenously and orally — targeting patients who acquire a pneumonia infection in a hospital, are put on an IV infusion, but then subsequently discharged. Currently, those patients would have to switch to a different, oral antibiotic after leaving the hospital. Patients receiving lefamulin, on the other hand, can be first given the drug intravenously in the hospital and then switched to the oral form after being sent home.
Perhaps more importantly, however, Nabriva says lefamulin can be used as a monotherapy and is specifically targeted to bacteria involved in the development of CABP. Targeted treatment of bacteria with fewer antibiotics should theoretically help address worries of engendering resistance with multiple broad-spectrum drugs.
Developing lefamulin hasn't come cheap. Nabriva's Broom estimates the company has spent over $100 million on its Phase 3 program for lefamulin, which includes the second LEAP 2 study.
Unlike LEAP 1, the second trial of lefamulin focuses on patients who are less sick and will compare all oral lefamulin treatment to oral moxifloxacin. Nabriva expects to complete enrollment of a targeted 738 patients by the end of this year, with topline results potentially available by spring 2018. If lefamulin succeeds in LEAP 2, Nabriva said it would then subsequently file for approval in the U.S.
After rocketing up over 95% in value at market open on Monday, shares in Nabriva pared back some of those gains to trade up about 60% over Friday's close.