Formulation boosts antibiotic efficacy
discovery that short pulses or bursts of antibiotic treatment are
more effective than continuous exposure in fighting bacterial
infections.
Par Pharmaceuticals has signed a letter of intent with Advancis Pharmaceutical to develop a pulsed formulation of the widely used antibiotic amoxicillin using the latter's Pulsys technology which could be filed for approval as early as next year.
In 1999, Advancis scientists demonstrated that bacteria exposed to antibiotics in pulses were eliminated more efficiently and tended not to develop resistant forms. Since then, the company has backed up this finding in a series of preclinical studies comparing pulsatile treatment regimens to traditional dosing in both in vitro and in vivo models, which have also revealed that pulsed regimens require lower drug concentrations to be effective.
Pulsys is an oral drug delivery technology designed to allow for pulsatile release of active drugs from a single once-daily dose. It takes the form of a compressed tablet that contains pellets designed to release drugs at different regions in the gastrointestinal tract.
Multiple pellet types of varying release profiles are combined in Pulsys products in a proportion so as to produce a constant escalation in plasma drug levels in the early portion of the dosing interval, as well as pulsatile delivery. The system uses well-studied excipients and common manufacturing processes, so there are few technological obstacles to making the tablets, according to Advancis.
Par already has a licensing agreement with Advancis that could see the development of a Pulsys formulation of clarithromycin, while GlaxoSmithKline is also looking at using Pulsys in a new formulation of Augmentin (amoxicillin plus clavulanate).
GSK is interested in using a Pulsys formulation of Augmentin to protect its franchise for the product, which lost patent protection in the US at the end of last year. This was a major blow for the company, as Augmentin is one of its biggest products, bringing in revenues of $825 million (€679m).
The new agreement with Par is for an improved version of amoxicillin on its own, which has long since lost patent protection. Around 60 million doses of the drug are prescribed each year around the world, and US sales alone are in the region of $500 million.
Amoxicillin is currently prescribed two or three times daily for ten days, and Advancis believes that its formulation could not only improve the efficacy of treatment, but also shorten its duration.
Under the terms of the letter of intent, Advancis would receive a fee of $5.0 million and a commitment from Par to fund all further development expenses in exchange for granting Par the exclusive right to sell Amoxicillin Pulsys and the co-exclusive right to market the product.
The two parties intend to jointly fund and run the marketing and sales programme and to share operating profits from product sales on an equal basis. Advancis would be responsible for manufacturing.
