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September 19, 2011 4:40 pm ET

New clinical and pre-clinical data on Merck’s odanacatib, an investigational cathepsin K (cat-K) inhibitor for the treatment of osteoporosis in post-menopausal women, were presented at the 33rd Annual Meeting of The American Society for Bone and Mineral Research (ASBMR) in San Diego. The data were presented in an oral presentation and five posters.

“Merck is pleased to continue building scientific knowledge about odanacatib with new data showing this investigational medication’s effects on increasing bone mineral density (BMD) and impacting bone strength and formation,” said Albert Leung, M.D., Ph.D., executive director, Clinical Research, Merck Research Laboratories. “Merck has a strong and long-standing commitment to the field of osteoporosis as evidenced by our large and rigorous Phase III program to evaluate the long-term efficacy and safety of odanacatib.”

Odanacatib selectively inhibits cathepsin K, the major enzyme in osteoclasts that is responsible for the breakdown of existing bone tissue. Odanacatib is currently in a large-scale Phase III clinical program to determine its safety and potential effects on hip, vertebral and non-vertebral fractures.

The following are highlights from the presentations at ASBMR. Abstracts can be viewed by visiting the ASBMR website at www.ASBMR.org.

Abstract # FR0453; Plenary Poster Session, September 16, 2011, 5:45 PM -7:00 PM PT/ Abstract # SA0453; Poster Session I, September 17, 2011, 11:00 AM – 1:00 PM PT – 5 Year Results of a Phase 2 Study of Odanacatib in Postmenopausal Women with Low Bone Mineral Density (BMD)

In a Phase IIb clinical study extending to five years, odanacatib continued to increase bone mineral density (BMD) and reduce bone resorption markers in postmenopausal women with low BMD (N=141). The two-year Phase IIb base study of postmenopausal women (mean age 63 years) with low bone mass (BMD T-scores initially between -2.0 and -3.5 at the lumbar spine, femoral neck, trochanter or total hip) was extended for three additional years to further assess the efficacy and long-term safety of odanacatib. The primary endpoint was BMD at the lumbar spine. Secondary endpoints included BMD at the femoral neck, trochanter, hip and distal radius; levels of bone resorption markers including urine NTx/creatinine, levels of bone formation markers including serum BSAP; and assessments of safety. Results from years four and five were presented.

In postmenopausal women who received odanacatib 50 mg weekly continuously for five years (N=13), there were BMD increases from baseline of 11.9 percent at the lumbar spine, 9.8 percent at the femoral neck, 10.9 percent at the hip trochanter, and 8.5 percent at the total hip. Additionally, women treated continuously with odanacatib 50 mg maintained a low level of urine NTx/creatinine (-67.4% from baseline) through five years of treatment; while levels of serum BSAP remained only slightly reduced relative to baseline (-15.3%). In women who were switched from odanacatib to placebo after the two-year base study (n=14), BMD returned to near baseline levels.

Because of the small sample size in each individual treatment group, groups were pooled for comparison on the incidence of adverse experiences in the placebo and odanacatib groups. Among the 114 women treated with the 10, 25 or 50 mg weekly dose of odanacatib at any time during the first three years of the study, 41 were treated with placebo and 73 with odanacatib 50 mg during years 4 to 5 of the study. The incidence of adverse experiences and serious adverse experiences were 81 percent and 20 percent, respectively, in the placebo group and 89 percent and 22 percent, respectively, in the odanacatib group. None of the women in the placebo group and two women (3%) in the odanacatib group discontinued the study drug due to an adverse experience. The incidence of skin-related adverse experiences was 17 percent and 12 percent in the placebo and odanacatib groups, respectively.

Abstract # 1030; Oral Session 05: New Approaches to Osteoporosis Treatment (Preclinical), September 17, 2011, 10:45 – 11:00 AM PT – Efficacy of the combination regimens of the cathepsin K inhibitor odanacatib versus alendronate with parathyroid hormone in estrogen-deficient rabbits

This preclinical study in estrogen-deficient rabbits (n=12/group) compared the effect of five different treatment regimens on bone mineral density (BMD), bone histology and bone strength: the combinations of human parathyroid hormone 1-34 (PTH) and odanacatib, PTH and alendronate, and the monotherapies including odanacatib, alendronate or PTH. The data showed that treatment with PTH+odanacatib resulted in the fastest rate of BMD gains.

After three months of treatment, both the PTH+odanacatib and PTH+alendronate groups increased lumbar vertebrae bone mineral density from baseline by 13.4 percent and 9 percent from baseline, respectively, while odanacatib, alendronate, and PTH resulted in increases from baseline of 8.7 percent, 2.9 percent, 1.9 percent, respectively. By six months of treatment, the PTH+ odanacatib and PTH+alendronate groups increased bone mineral density from baseline in the lumbar vertebrae by 17.6 percent and 18.4 percent, respectively. Odanacatib, alendronate and PTH monotherapies increased lumbar spine bone mineral density from baseline by 11.3 percent, 8.3 percent, and 6.2 percent, respectively. Bone histology showed that although both the PTH+odanacatib and PTH+alendronate combinations resulted in increases in BMD, the PTH+alendronate combination eventually halted bone formation in the trabecular lumbar vertebrae, whereas the PTH+odanacatib combination increased BMD and bone formation rate. Positive correlations between BMD and bone mineral content and bone strength were seen in both the hip and the spine.

Abstract # FR0473; Plenary Poster Session, September 16, 2011, 5:45 PM -7:00 PM PT/ Abstract # SA0473; Poster Session I, September 17, 2011, 11:00 AM – 1:00 PM PT – Differential effects of odanacatib and alendronate on bone turnover in the femoral neck of adult ovariectomized rhesus monkeys

This preclinical study evaluated the effects on bone mass and turnover in the femoral neck of ovariectomized rhesus monkeys (n=48) after 20 months of treatment with odanacatib, alendronate or placebo. Both odanacatib and alendronate significantly decreased trabecular bone formation rate at 12 months (p<0.01) and 20 months (p<0.05) compared to placebo. On the cortical bone surface, odanacatib significantly increased the cortical bone formation rate, a parameter which was not affected by treatment with either alendronate or placebo. The increased long-term bone formation rate with odanacatib, determined within 8-months of odanacatib treatment, resulted in a significant increase in cortical thickness by 23 percent (p<0.05), cortical area per tissue area by 18 percent (p<0.05) and a decrease in marrow area per tissue area by 11 percent (p<0.05) versus placebo.

Abstract # MO0472; Poster Session III, September 19, 2011 from 11:30 AM – 1:30 PM PT Effects of odanacatib versus alendronate on bone remodeling and biomechanical properties of the lumbar spine in estrogen-deficient rhesus monkeys.

This preclinical study evaluated the effects of odanacatib and alendronate on bone mineral density (BMD), bone turnover, strength and collagen organization in the lumbar spine of estrogen-deficient rhesus monkeys (n=48). Compared to placebo, significant increases in lumbar spine BMD were observed in the odanacatib (6.7%) and alendronate groups (6.4%). Both odanacatib and alendronate were also shown to significantly reduce (p<0.001) trabecular bone remodeling rate as compared to placebo. Increases in lumbar spine strength were also shown in the odanacatib and alendronate treated groups as compared to placebo.

Abstract # MO0037; Poster Session III, September 19, 2011, 11:30 AM – 1:30 PM PT Differentiation of treatment effects of odanacatib from alendronate in ovariectomized rhesus monkeys using voxel based morphometry of quantitative computed tomography images

This preclinical study examined volumetric bone mineral density (vBMD) in ovariectomized rhesus monkeys (n=48) treated with odanacatib, alendronate or placebo. Both odanacatib and alendronate produced significant increases in vBMD in the femoral neck from baseline; however, the positive effect of odanacatib was shown to be greater on cortical bone compared to alendronate.

Additionally, the following data will also be presented:

— Abstract # SU0066 – Evaluation of HR-pQCT in non-human primates for monitoring effect of odanacatib on bone microarchitecture

About FOSAMAX® and FOSAMAX PLUS D® (alendronate sodium and cholecalciferol)

FOSAMAX (alendronate sodium) and FOSAMAX PLUS D (alendronate sodium/cholecalciferol) are indicated for the treatment of osteoporosis in postmenopausal women. The safety and effectiveness of FOSAMAX and FOSAMAX PLUS D for the treatment of osteoporosis are based on clinical data of four years duration.

Important Safety Information about FOSAMAX and FOSAMAX PLUS D

FOSAMAX and FOSAMAX PLUS D should not be used in patients with certain disorders of the esophagus that delay emptying, who are unable to stand or sit upright for at least 30 minutes, who have low levels of calcium in their blood, or in patients who are allergic to FOSAMAX or FOSAMAX PLUS D.

Some patients may develop severe digestive reactions including irritation, inflammation or ulceration of the esophagus. 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.

Osteonecrosis of the jaw, generally associated with tooth extraction and/or local infection, with delayed healing, has been reported in patients taking bisphosphonates, including FOSAMAX and FOSAMAX PLUS D. Patients who develop osteonecrosis of the jaw while on bisphosphonate therapy should receive care by an oral surgeon.

New or unusual hip, thigh or groin pain should be evaluated, as atypical femoral (thigh bone) fractures have been reported in patients taking bisphosphonates, including FOSAMAX and FOSAMAX PLUS D.

The most common adverse reactions for FOSAMAX and FOSAMAX PLUS D (incidence ≥3%) are abdominal pain, acid regurgitation, constipation, diarrhea, dyspepsia, musculoskeletal pain, nausea.

About Merck

Today’s Merck is a global healthcare leader working to help the world be well. Merck is known as MSD outside the United States and Canada. Through our prescription medicines, vaccines, biologic therapies, and consumer care and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to healthcare through far-reaching policies, programs and partnerships. For more information, visit www.merck.com.

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The following factors, among others, could cause actual results to differ from those set forth in the forward-looking statements: the possibility that the expected synergies from the merger of Merck and Schering-Plough will not be realized, or will not be realized within the expected time period; the impact of pharmaceutical industry regulation and health care legislation; the risk that the businesses will not be integrated successfully; disruption from the merger making it more difficult to maintain business and operational relationships; Merck’s ability to accurately predict future market conditions; dependence on the effectiveness of Merck’s patents and other protections for innovative products; the risk of new and changing regulation and health policies in the United States and internationally and the exposure to litigation and/or regulatory actions.

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The Prescribing information and Medication Guides for FOSAMAX and FOSAMAX PLUS D are available at:

www.merck.com/product/usa/pi_circulars/f/fosamax/fosamax_pi.pdf,

www.merck.com/product/usa/pi_circulars/f/fosamax/fosamax_mg.pdf, www.merck.com/product/usa/pi_circulars/f/fosamax/fosamax_plus_d_pi.pdf, and

www.merck.com/product/usa/pi_circulars/f/fosamax/fosamax_plus_d_mg.pdf.

FOSAMAX® and FOSAMAX PLUS D® are registered trademarks of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Whitehouse Station, N.J., U.S.A.

 

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