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New Data on Odanacatib, Merck?s Investigational Cat-K Inhibitor for Osteoporosis, Presented at the Annual Meeting of The American Society for Bone and Mineral Research

Data show potential of investigational treatment for osteoporosis in preventing bone loss and increasing bone strength

TORONTO, 18 Oct 2010 – New data on odanacatib, the investigational cathepsin-K (Cat-K) inhibitor in development by Merck for the treatment of osteoporosis in postmenopausal women, were presented at the 32nd Annual Meeting of The American Society for Bone and Mineral Research (ASBMR) in Toronto, Canada. The data from clinical and pre-clinical studies, presented in two oral presentations and six posters, continue to provide further information on the potential of odanacatib to increase bone density, cortical thickness and bone strength when treating osteoporosis.

“We are pleased to be able to have such a robust presentation of new data for odanacatib at the 2010 ASBMR Annual Meeting,” said Albert Leung, M.D., Ph.D., Executive Director, Clinical Research, Merck Research Laboratories. “The clinical and preclinical data being presented show long-term increases in bone mineral density and impact on bone formation with odanacatib therapy. We are continuing our strong and long-standing commitment to the field of osteoporosis with a large and rigorous Phase III program to evaluate the long-term efficacy and safety of odanacatib.”

Odanacatib is a cathepsin-K inhibitor that selectively inhibits the cathepsin-K enzyme. Cathepsin-K is known to play a central role in the function of osteoclasts, which are cells that break down existing bone tissue, particularly the protein components of bone. Inhibition of cathepsin-K is a novel approach to the treatment of osteoporosis. Odanacatib is currently in Phase III clinical trials and is being evaluated in a large-scale clinical study to determine potential effects on vertebral, hip and non-vertebral fractures.

Following are highlights from four of the eight presentations at ASBMR. Abstracts can be viewed by visiting the ASBMR website at

Abstract # 1247; Oral Session 42, October 18, 2010 4:30 PM - 4:45 PM ET - Effect of Odanacatib on Bone Density and Bone Turnover Markers in Postmenopausal Women with Low Bone Mineral Density: Year 4 Results

In a Phase IIb clinical study odanacatib reduced bone resorption markers and progressively increased bone mineral density during four years of treatment. A two-year base study of postmenopausal women with low bone mass (BMD T-scores between -2.0 and -3.5 at the lumbar spine, femoral neck, trochanter or total hip) was extended for two additional years in 141 women to further assess efficacy and long-term safety of odanacatib vs. placebo. The primary endpoint was bone mineral density (BMD) at the lumbar spine. Secondary endpoints included BMD at total hip and hip sub-regions, and 1/3 radius; levels of bone formation markers serum CTx and BSAP; and assessments of safety.

In postmenopausal women who received odanacatib 50 mg weekly for 4 years (N=13), an increase in BMD of 2.8 percent at the lumbar, and 2.7 percent at the hip were demonstrated between years 3 and 4 of treatment. Over four years of treatment, these women had increases in lumbar spine (10.7 percent) and hip (8.3 percent) BMD from baseline. Levels of serum CTx (-41 percent from baseline) remained low whereas BSAP (-2 percent from baseline) remained relatively unchanged between years 3 and 4 of the study. In women who received odanacatib for two years during the base study but were switched to placebo for the two-years extension (n=38), the effects on bone turnover markers and BMD were reversed, returning to, or near, baseline. Most frequently reported adverse events during the year four extension period included nasopharyngitis (13 percent odanacatib vs. 17 percent placebo) and pain in extremity (10 percent odanacatib vs. 2.4 percent placebo).

Abstract # FR0435; Plenary Poster Session, October 15, 2010 5:45 PM - 7:00 PM ET - A Multi-Modality Imaging Comparison of Odanacatib to Alendronate in the Ovariectomized Rhesus Monkey

This pre-clinical analysis was designed to evaluate the efficacy of odanacatib compared to alendronate in the estrogen-deficient model of the ovariectomized rhesus monkey (n=48) by multiple imaging modalities. To confirm analysis endpoints of efficacy in relation to bone strength, macro- and micro-architectural imaging markers were measured at multiple anatomic locations. In this study, in-vivo imaging markers showed that odanacatib was superior to alendronate as measured by volumetric bone mineral density in the hip (11 percent and 6.8 percent, respectively; p=0.028), radius (13.9 percent and 2 percent, respectively; p<0.001) and tibia (12.7 percent and 8.2 percent, respectively; p<0.001), and cortical thickness in the radius (6.7 percent and 2.9 percent, respectively; p=0.039) and tibia (5.6 percent and 2.4 percent, respectively; p=0.014) of overiectomized rhesus monkeys. The application of imaging parameters relevant to fracture risk at multiple skeletal sites will be evaluated in odanacatib clinical trials.

Abstract # FR0440; Plenary Poster Session, October 15, 5:45 PM - 7:00 PM ET - Quantitative Computed Tomography Based Finite Element Analysis to Estimate In-Vivo Bone Strength of Proximal Femur in Odanacatib Treated Rhesus Monkeys

This pre-clinical analysis was designed to examine in-vivo estimates of bone strength in the proximal femur in ovariectomized rhesus monkey (n=48) treated with odanacatib, alendronate or vehicle. Percent change of bone strength from baseline (pre-treatment) for the odanacatib, alendronate and vehicle groups at 18 months were 15%, 9%, and 1%, respectively (odanacatib vs. vehicle p<0.01). Differences were also seen in volumetric BMD (vBMD) at the femoral neck, which showed significant increases due to odanacatib and alendronate treatment after 18 months of treatment (odanacatib increased 12 percent, alendronate increased 7 percent, vehicle increased 2%; odanacatib vs. vehicle p<0.01). Cortical thickness of the femoral shaft also showed a significant increase due to odanacatib and alendronate treatment, with odanacatib being the most efficacious at 12 and 18 months (odanacatib vs. vehicle, p<0.01; alendronate vs. vehicle, p<0.01).

Abstract # SA0437; Poster Session I, October 16, 2010 11:30 AM - 1:30 PM ET - Differential Effects of Odanacatib Compared to Alendronate on Bone Turnover Markers in Adult Ovariectomized Rhesus Monkeys.

This pre-clinical analysis in ovariectomized rhesus monkeys (n=64) investigated the effects of odanacatib in preventing bone loss compared the bisphosphonate alendronate. In this study, odanacatib was as effective as alendronate in suppressing bone resorption markers uNTx and sCTx to 65-75 percent below baseline, which was the primary endpoint of the study. However, odanacatib treatment was associated with significantly less reduction of bone formation markers than alendronate and increased a marker for osteoclast number in this animal model. The findings from this study have been consistent with previous observations in a Phase II study with osteoporotic women.

Additional Studies

Other studies presented by Merck on odanacatib at ASBMR include:

· Abstract # SU0250 - Effects of Odanacatib Treatment on Osteoclast Vesicular Trafficking During Bone Resorption

· Abstract # SU0438 - Lack of Intermittent PTH Response to Daily Administration of Odanacatib in Adult-Ovariectomized Rhesus Monkeys

· Abstract #1171 – Comparing the Effects of Odanacatib versus Alendronate on Bone Turnover of Transilial Biopsy in Adult Ovariectomized Rhesus Monkeys

· Abstract # MO0410 - Semi-Mechanistic PK/PD Model of the Effect of Odanacatib, a Cathepsin K Inhibitor, on Bone Turnover to Characterize Lumbar Spine Bone Mineral Density in Two Phase II Studies of Postmenopausal Women

Important information about alendronate (FOSAMAX®) FOSAMAX, like other bisphosphonate containing products, should be used with caution in people with certain stomach or digestive problems. FOSAMAX should not be used if the patient has certain disorders of the esophagus that delay emptying or if the patient is unable to stand or sit upright for at least 30 minutes. In addition, FOSAMAX should not be used in patients with severe kidney disease or low levels of calcium in their blood, in patients who are allergic to FOSAMAX or in patients who are pregnant or nursing. Patients who have difficulty swallowing liquids should not take FOSAMAX oral solution. Some patients may develop severe digestive reactions including irritation, inflammation or ulceration of the esophagus. The risk of severe esophageal experiences appears to be greater in patients who fail to follow dosing instructions (see prescribing information for more details). Patients who experience new or worsening heartburn, difficulty or pain when swallowing or chest pain should stop taking the drug and call their doctor right away. Patients who develop severe bone, joint and/or muscle pain at any time should contact their doctor. FOSAMAX may cause jawbone problems, which may include infection, and delayed healing after teeth are pulled. The standard dosing regimen for FOSAMAX includes swallowing the tablet with six to eight ounces of plain water the first thing upon arising for the day and at least 30 minutes before the first food, beverage or medication of the day. After swallowing FOSAMAX, patients should not lie down for at least 30 minutes and not until after consuming their first food of the day. Patients should not chew or suck on a tablet of FOSAMAX. Prescribing information is available at for FOSAMAX® (alendronate sodium) Tablets and Oral Solution. Patient product information is available at for FOSAMAX® (alendronate sodium) Tablets and Oral Solution, Once Weekly; and at for FOSAMAX® (alendronate sodium) Tablets and Oral Solution, Once Daily. Prescribing information and patient product information for these products is also attached.

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Posted: November 2010