Drug enters Phase I to test MRSA efficacy

Novexel has announced it is to put forward its novel small molecule antibiotic into Phase I clinical development representing a new class of antibacterials to treat hospital-based infections caused by gram positive pathogens.

The drug candidate NXL101 is a bacterial topoisomerase/gyrase inhibitor that has already shown potent activity against Gram-positive bacteria including methicillin, quinolone, vancomycin and macrolide resistant strains.

According to the company, levels of penicillin non-susceptibility in S.pneumoniae found in several surveys are around 30 per cent in Western Europe (exceeding 50 per cent in some countries such as France), 34 per cent in USA and 81 per cent in Japan.

In addition, Nosocomial methicillin resistant S.aureus, Methicillin resistant Staphylococcus aureus (MRSA) strains, often multi drug resistant, (MDR) are prevalent in some European areas such as the Mediterranean region and the UK (>forty per cent) whereas they are rare in Scandinavian hospitals (

Novexel will be making a poster presentation at the 45th annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC), which takes place in San Francisco on 27-30 September 2006.

Researchers will present in vivo efficacy data in which the in vivo efficacy of NXL101 against S. aureus was assessed in murine models of septicaemia and thigh muscle infections compared to moxifloxacin (MOX), linezolid (LIN) and vancomycin (VAN), with a focus on multi-resistant strains.

Mice were infected with one of eight S.aureus strains; two susceptible and six methicillin resistant (MRSA). A second group of mice were inoculated in the thigh muscle with one of six S.aureus strains (one MSSA, five MRSA).

Results revealed that NXL101 was effective in a range similar to that of linezolid (LIN) and vancomycin (VAN). NXL101 also proved superior to moxifloxacin(MOX).

Results from the thigh muscle infection showed that for the 6 strains tested, NXL101 reduced the bacterial burden compared to untreated controls.

This was similarly efficacious as LIN and VAN, and significantly more effective than MOX.

News of these results bodes well for the future of antibiotic development, as new approaches to combat resistance are a clear medical need not only in Europe but also worldwide.

Recent findings suggest that MRSA is emerging as a community-acquired pathogen with twenty per cent of S.aureus isolated were MRSA in a survey in North America.

Also instances of glycopeptide resistant S.aureus have been monitored in several countries, leaving therapeutic choice extremely limited.

Other Gram- positives such as the enterococci have acquired resistance to several antibiotic classes, including aminoglycosides, glycopeptides (twenty five per cent in USA), and ampicillin (seventy one per cent in Europe).

The emergence of these resistant bacteria is made more alarming due to their readiness to spread in hospitals.