CRES Statins
Circ Pharma is developing a number of unique Controlled Release Statin (CRES) product candidate formulations for the treatment of hypercholesterolemia with very significant revenue potential and market opportunity. Global sales of statins currently exceed $26 billion per annum.Circ Pharma has developed an initial formulation of its lead CRES product candidate and anticipates commencing a phase II proof of concept study in late 2009. Based on interaction with US regulatory approval will be a 505(b)(2) new drug application (NDA) potentially resulting in a shorter development and regulatory approval pathway and reduced development cost compared with a standard NDA.
The basic concept underlying CRES statins is that by controlling the amount and rate of statin delivered to the liver from the gut, the hepatic exposure (hepatic bioavailability) can be increased and the systemic exposure (systemic bioavailability) can be decreased. The benefits of this approach are enhanced lipid-lowering efficacy without an associated increase in systemic concentrations and side-effects. These benefits will be established by demonstrating an enhanced LDL-C lowering dose-response curve without increased systemic exposure. This effectively represents an improvement of the therapeutic index for the statins.
The achievement of better lipid-lowering at typical low to medium doses without increased systemic exposure will add to the acceptability and safety of statin therapy. This enhanced efficacy without increased systemic exposure at medium to high doses will allow more aggressive lipid lowering targets to be met, particularly for 'at risk' patients, without the increased safety risk of traditional dose escalation.
Benefits of CRES include:
- Allows dosing of statins to higher doses to achieve maximal lipid lowering effects,
- Allows improved lipid-lowering at lower doses e.g. OTC uses,
- Enhanced lipid lowering efficacy without an associated increase in systemic exposure,
- Allows CRES formulations of lower potency statins to compete with standard formulations of higher potency statins
- Allows more aggressive LDL-C lowering targets to be achieved,
- Reduced potential for adverse events (AE's),
- Reduced potential for serious AE's, and
- Safer co-administration with other agents.