MER-103
MER 103 is an innovative dosage form of alendronate (Fosamax®, Merck), which uses Merrion's proprietary absorption enhancing technology (GIPET™) to provide significant benefits to patients and medical practitioners.
The Market
Bisphosphonates are the most widely used therapy for osteoporosis. Bisphosphonate sales were >$5Bn worldwide in 2005. Fosamax® sales were $3.2Bn in 2005; the leading competitor, Actonel® (P&G/sanofi-aventis), had sales of $1.3Bn in 2005.
Once-weekly formulations of the Merck and P&G products dominate usage at present. Boniva® (Roche/GSK) was launched as a once monthly product in 2005 and has gained US market share.
A key issue in this marketplace is adherence to therapy. A large patient survey by the International Osteoporosis Foundation has shown that almost 60% of patients dosed weekly discontinue therapy within the first year, and that side effects and the complexity of dosing are the major patient reasons for discontinuing treatment.
Fosamax® must be taken at least 30 minutes before the first food, beverage, or medication of the day with plain water only. The fasted bioavailability of Fosamax® is 0.6% and it is negligible if taken with food. Patients are cautioned to sit or stand upright for 30 minutes after taking their medication in order to reduce the potential for oesophageal irritation, and may have to discontinue therapy if they suffer reflux.
Product Description
The patented MER 103 formulation features GIPET™ enhancers to substantially improve bioavailability and enteric coating to release the drug in the small intestine. These improvements allow us to simplify the current complex dosing regimen, avoid GI side effects, significantly reduce the dose and potentially reduce the frequency of administration (e.g. monthly).
Project Status
Several clinical pharmacology studies have demonstrated successfully the proof of concept for the product. In the most recent, a Phase II single dose four way crossover study was conducted in 16 post-menopausal women to evaluate the relative bioavailability of MER 103, under several fed or fasted conditions. An oral dose of Fosamax®, was the reference drug, taken as per label. Based on urinary excretion data for alendronate, MER 103 gave an increase in relative bioavailability of approximately 15 fold when dosed at night time, 12 fold when dosed fasted overnight and 3 fold when dosed with a high fat breakfast.
This study demonstrates that, when given after an overnight fast, 6mg of MER 103 is equivalent to 70mg of Fosamax®.
There were no serious adverse events in this study, or in any other clinical study conducted with MER 103 formulations. Importantly, there were no serious adverse events related to gastrointestinal irritation or discomfort reported after dosing with the MER 103 formulation.
The MER 103 formulation has demonstrated its potential to improve patient convenience and reduce side effects by:
- Avoiding side effects in the stomach and oesophagus by being released in the small intestine.
- Allowing more convenient patient options as to when and how MER 103 is taken.
- Reducing the amount of drug that needs to be taken.
Manufacturing
There are no special equipment requirements for manufacturing the new formulation.
Patent Status
Merrion's GIPET™ technology is covered under issued and in-process patents, giving considerable patent life. A product specific patent is in process for MER 103.
Clinical Data for MER-103 was presented at The North American Menopause Society (NAMS) 2007 Annual Meeting, held on October 3-6, 2007, in Dallas.
For more information or to view a copy of the poster, please click here.
