Aurograb®
Aurograb® is a "grab" targeting Staphylococcus aureus including MRSA and the recently emerged VISA. Staphylococcus aureus is the bacterium responsible for the largest proportion of hospital-acquired bacterial infections. MRSA is now endemic in hospitals around the world with an estimated 1.5 million cases per year worldwide. MRSA causes significant morbidity with mortality from MRSA bloodstream infections of up to 50 per cent.
Vancomycin is an antibiotic of last resort being a cause of nephrotoxicity, ototoxicity and bone marrow toxicity. Moreover, intermediate sensitivity to vancomycin has recently surfaced among MRSA strains in Japan, the USA and Europe. The emergence of VISA has been described by The Lancet as an “apocalypse now” scenario and highlights the need for new and more effective therapies.
cGMP manufacture of Aurograb® was completed in June 2001 involving fermentation, downstream processing and freeze drying batches of the final purified product. Pre-clinical studies were successfully completed in November 2001 and a CTX was successfully applied for from the MCA in January 2002. Clinical trials commenced in mid 2002.
Aurograb® has the following properties as an antistaphylococcal agent:
- intrinsic activity against staphylococci;
- synergistic activity with vancomycin: the combined use of the two agents together giving greater activity than either agent alone; and
- a broad spectrum of activity against different strains of Staphylococcus aureus including the currently circulating epidemic strains of MRSA and VISA.
This activity has been demonstrated using laboratory assays analogous to those used to test antistaphylococcal antibiotics, including minimum inhibitory levels and models of the infection. Given its synergy with vancomycin, the company anticipates that Aurograb® will be of particular benefit when prescribed in combination with vancomycin in the treatment of MRSA infections, both increasing efficacy and inhibiting the emergence of VISA.
In June 2006 the company completed a double-blind placebo-controlled phase III clinical trial. The study carried out in a total of 35 centres in 6 European countries and involved the recruitment of 161 adult hospitalized patients with deep-seated staphylococcal infections. The trial compared the effects of Aurograb® in combination with vancomycin versus vancomycin alone in the treatment of MRSA infections.
This trial follows the earlier phase IIb study which was completed in June 2003 and found the drug to be well tolerated and demonstrated a profile that supports likely activity against MRSA in man. Aurograb® has activity on its own against strains of MRSA, but when combined with vancomycin, the current “gold standard” treatment, is more effective than either drug used on its own. The activity is also evident in strains with partial resistance to vancomycin or linezolid. Fully resistant strains to vancomycin have also been reported.