Merck Researchers Present BMD Data from a Phase II Study of Odanacatib, Merck’s Investigational Cat-K Inhibitor for Post-Menopausal Osteoporosis


October 13, 2012 11:15 am ET

Odanacatib Significantly Increased BMD Following Prior Alendronate Treatment

Merck (NYSE: MRK), known as MSD outside the United States and Canada,
today announced results from a Phase II trial for odanacatib, an
investigational cathepsin K (cat-K) inhibitor in development for the
treatment of osteoporosis in post-menopausal women. The results were
presented today at the 34th Annual Meeting of the American
Society for Bone and Mineral Research.

In the study, treatment with odanacatib (compared to placebo)
significantly increased Bone Mineral Density (BMD) over a two-year
period in post-menopausal osteoporotic women who previously had three or
more years of treatment with alendronate. Patients were allowed to have
been off alendronate therapy for up to three months immediately prior to
enrollment in the study.

“Odanacatib works differently than other treatments for osteoporosis by
targeting cat-K, a specific enzyme within bone cells,” said Albert
Leung, M.D., Ph.D., executive director, clinical research, Merck
Research Laboratories. “We’re excited about these results because
understanding the effects of odanacatib in a population of
post-menopausal women previously treated for osteoporosis is important
to clinicians.”

Study evaluated efficacy and safety of odanacatib following treatment
with alendronate

This study was a randomized, double-blind, placebo-controlled,
multi-center, 24-month trial of odanacatib in 243 women with
post-menopausal osteoporosis who had been previously treated with
alendronate (dosed daily or weekly) for ≥3 years. Participants were at
least 60 years of age with low BMD T-scores (≤–2.5 and >-3.5) at any hip
site (femoral neck, trochanter, or total hip) without a history of
fragility fracture, or had BMD T-scores ≤-1.5 and > -3.5 at any hip
site, with a history of fragility fracture (except hip fracture). The
patients were randomized in a 1:1 ratio to receive odanacatib 50 mg once
weekly or placebo for 24 months. All patients received vitamin D3 (5600
IU/week) and also calcium supplementation, if needed.

The study evaluated the effects of odanacatib 50 mg once weekly on the

  • Femoral neck BMD change from baseline compared to placebo over 24
    months (primary endpoint)
  • Femoral neck BMD compared to baseline over 24 months (key secondary
  • BMD at hip trochanter, total hip, lumbar spine and distal forearm
  • Biochemical markers of bone resorption and formation at months 12 and
  • Clinical and laboratory assessment of safety and tolerability

BMD was assessed by DXA at baseline, 6, 12 and 24 months. This study was
not designed to evaluate the effect of odanacatib on fractures.

Results showed odanacatib significantly increased BMD compared to

In the odanacatib group, BMD changes from baseline at 24 months were
significantly different versus placebo at all three hip sites (+1.73%,
+1.83%, +0.83% for the femoral neck, hip trochanter, and total hip,
respectively, vs. -0.94%, -1.35%, -1.87% with placebo), and the lumbar
spine (+2.28% vs. -0.30% change with placebo). At the distal forearm,
BMD changes from baseline at 24 months were -0.92% and -1.14%. The
difference versus placebo at the distal forearm (+0.22%) was not
statistically significant.

The overall incidence of adverse events, including those that were
considered drug-related or serious, were similar between treatment
groups. Treatment discontinuations due to adverse events were 9.0
percent for patients receiving odanacatib and 3.3 percent for patients
receiving placebo. The most common clinical adverse events in patients
receiving odanacatib and placebo, respectively, were urinary tract
infection (11.5%, 16.5%), back pain (11.5%, 9.9%), arthralgia (9.0%,
9.9%), fractures (4.9%, 13.2%), bronchitis (5.7%, 4.1%), nasal
pharyngitis (3.3%, 5.8%), and upper respiratory infection (4.1%, 0.8%).

About Odanacatib

In osteoporosis, bone loss occurs because of an imbalance in bone
remodeling (the rate of bone resorption exceeds that of bone formation).
Osteoclasts, cells that resorb bone, secrete signaling factors to
stimulate osteoblasts, cells that form bone. Odanacatib selectively
inhibits cat-K, the primary enzyme in the osteoclasts that digests
proteins during bone resorption. Progressive increases in bone mineral
density have been demonstrated with odanacatib.

In July 2012, Merck announced it planned to begin closing the Phase III
trial assessing fracture risk reduction with odanacatib, at the
recommendation of the study’s Data Monitoring Committee (DMC), after its
first planned interim analysis showed robust efficacy and a favorable
benefit-risk profile. The DMC noted that safety issues remain in certain
selected areas and made a recommendation with respect to following up on
them. Merck’s previously announced plan to conduct a blinded extension
trial will allow further monitoring of the issues. The extension trial
will also continue to measure efficacy.

Final results of the study will be submitted for presentation and
publication in 2013 once the data analysis is complete. Merck
anticipates submitting regulatory applications for odanacatib in the
United States and European Union (EU) in the first half of 2013, and in
Japan in the second half of 2013.

About Merck

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well. Merck is known as MSD outside the United States and Canada.
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Kelley Dougherty, 908-423-4291
Megan Wilkinson, 267-305-6463
Carol Ferguson, 908-423-4465

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