Phaxan™ is an intravenous general anaesthetic and sedative containing alphaxalone as the active pharmaceutical ingredient. Alphaxalone is a neuroactive steroid anaesthetic. It is a pregnanedione with no endocrine hormonal activity. This water-insoluble drug was initially formulated using CremophorEL and marketed as Althesin® from 1972 to 1984. It was found to be a safe and versatile intravenous anaesthetic used in clinical practice in anaesthesia and intensive care in many countries until it was withdrawn from clinical practice because of hypersensitivity to the CremophorEL.
Many subsequent attempts to make an aqueous formulations of neuroactive steroids suitable for human use have failed. Drawbridge Pharmaceuticals’ proprietary and patented formulation, Phaxan™, is a solution of alphaxalone 10mg/ml dissolved in 13% SBECD (7- sulfobutylether β-cyclodextrin); a molecule with a lipophilic cavity that enables drug dispersal in water for human use. The use of SBECD as the excipient preserves all of the advantages and utility of alphaxalone so evident when it was formulated as Althesin® but now avoiding all of the problems caused by the CremophorEL. The properties of the new anaesthetic preparation:
- Phaxan™ is a clear aqueous solution which is easy to manufacture, sterilise, and it remains stable in solution
- Phaxan™ has fast onset and offset equal with propofol; the dose of alphaxalone formulated as Phaxan™ needed for anaesthesia is the same as reported for alphaxalone formulated as Althesin® with the same speed of onset and duration of anaesthetic effect
- Phaxan™ has no accumulation on repeat dosing, with no active metabolites
- Phaxan™ is twice as potent as the current industry leader propofol in causing sedation and anaesthesia
- Phaxan™ causes less blood pressure fall than propofol
- Phaxan™ has a high therapeutic index (six times higher than propofol) and wide therapeutic margin which is the largest ever recorded for any anaesthetic since 1846
- Phaxan™ is neuroprotective at normal anaesthetic doses in foetal and adult brains
- Phaxan™ and related compounds are the subject of a family of patents with a priority date 2010
A proof of concept clinical trial comparing the anaesthetic properties of Phaxan™ and propofol was commenced in December 2013 and completed in April 2014. This was a dose finding double blind comparison in male volunteers that showed the advantages of Phaxan™ over propofol, highlighted in preclinical studies, were also realisable in humans. With its improved safety profile compared with propofol, we believe Phaxan™, has the potential to become the new gold standard drug of choice for intravenous anaesthesia, procedural sedation and intensive care sedation.