Date: 2016-06-20
Type of information: Presentation of results at a congress
phase: preclinical
Announcement: presentation of results at the ASM Microbe 2016 Conference
Company: Nabriva Therapeutics (Austria)
Product: lefamulin (BC 3781)
Action mechanism: antibioctic/pleuromulin derivative. Lefamulin (BC 3781) belongs to the first generation of pleuromutilins to combine excellent systemic bioavailability with substantial activity against Gram-positive pathogens, and fastidious Gram-negative pathogens plus atypical pathogens. Pleuromutilins interfere with bacterial protein synthesis via a specific interaction with the 23S rRNA of the 50S bacterial ribosome subunit. These antibacterials have a distinct anti-bacterial profile. Their unique mechanism of action implies a very low probability of cross resistance with other antibacterials. In an industry first, Nabriva\'s world class medicinal chemistry expertise achieved the development of intravenous and orally available pleuromutilins clearing the way for i.v. and oral therapy with this antibiotic class. This achievement constitutes a significant milestone in providing appropriate medication for the treatment of life-threatening bacterial infections offering a distinctly different class of antibiotics for the treatment of bacterial diseases. Lefamulin is highly active against multi-drug resistant (MDR) pathogens including Methicillin resistant Staphylococcus aureus (MRSA), MDR Streptococcus pneumoniae, Vancomycin resistant Enterococcus faecium. Nabriva has initiated two global, registrational Phase 3 clinical trials investigating lefamulin treatment in patients with moderate-to-severe Community Acquired Bacterial Pneumonia (CABP). ((NCT02813694 and NCT02559310)
Disease:
Therapeutic area: Infectious diseases
Country:
Trial details:
Latest
news:
• On June 20, 2016, Nabriva Therapeutics announced research findings for lefamulin, a novel semi-synthetic antibiotic Nabriva is developing to be the first pleuromutilin antibiotic available for systemic administration in humans. The company has reported in vitro data at the ASM Microbe 2016 Conference. Lefamulin demonstrated excellent in vitro activity against all tested isolates of Mycoplasma pneumoniae, a common cause of CABP associated with significant morbidity and mortality. Importantly, lefamulin’s in vitro activity against M. pneumoniae was unaffected by resistance to macrolides, which have been widely used against M. pneumoniae.
In Vitro Activity of Lefamulin Against Macrolide-Susceptible (MSMP) and Macrolide-Resistant Mycoplasma pneumoniae (MRMP) from the United States, Europe, and China (Abstract 3972) - Key Findings:
Lefamulin and four comparator antibiotics were tested against 50 unique isolates of M. pneumoniae, including 36 macrolide-resistant isolates obtained between 2009 and 2013 from the US and China. Lefamulin demonstrated potent in vitro activity against M. pneumoniae, regardless of resistance phenotype, inhibiting all 50 strains at concentrations < 0.004 µg/mL. Importantly, lefamulin was shown to have the lowest MIC90 value against all 36 strains of Macrolide-resistant M. pneumoniae (MRMP) compared with azithromycin, erythromycin, moxifloxacin and tetracycline.
Lefamulin’s bactericidal (bacterial killing) effect against eight isolates, including six MRMP isolates was also evaluated. The minimum bactericidal concentration (MBC) measured were as follows:
Strain
Susceptibility
MIC [µg/mL]
MBC [µg/mL]
1
Macrolide-susceptible
0.0005
0.002
2
Macrolide-susceptible
0.001
0.002
3
Macrolide-resistant
0.001
0.004
4
Macrolide-resistant
0.002
0.008
5
Macrolide-resistant
0.002
0.008
6
Macrolide-resistant
0.001
0.004
7
Macrolide-resistant
0.002
0.004
8
Macrolide-resistant
0.002
0.008
