ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 2268

Odanacatib Anti-Fracture Efficacy and Safety in Postmenopausal Women with Osteoporosis: Results from the Phase III Long-Term Odanacatib Fracture Trial

Michael R. McClung1, Bente Langdahl2, Socrates Papapoulos3, Kenneth G. Saag4, Silvano Adami5, Henry G. Bone6, Tobias de Villiers7, Douglas P. Kiel8, Annie Kung9, Prasanna Kumar10, Sung-Kil Lim11, Xu Ling12, Kurt Lippuner13, Carlos Mautalen14, Toshitaka Nakamura15, Jean-Yves Reginster16, Ian R. Reid17, José Adolfo Rodríguez-Portales18, Christian Roux19, Jesus Walliser20, Nelson B. Watts21, José R. Zanchetta22, Cristiano A.F. Zerbini23, Andrea Rybak-Feiglin24, Dosinda Cohn24, Carolyn A. DaSilva24, Rachid Massaad25, Arthur Santora24, Boyd B. Scott24, Nadia Verbruggen25, Albert Leung26 and Antonio Lombardi24, 1Oregon Osteoporosis Center, Portland, OR, 2Aarhus University Hospital, Aarhus, Denmark, 3Leiden University Medical Center, Leiden, Netherlands, 4Immunology & Rheumatology, The University of Alabama at Birmingham, Birmingham, AL, 5Rheumatology Department, University of Verona, Verona, Italy, 6Michigan Bone and Mineral Clinic, Detroit, MI, 7Stellenbosch University, Stellenbosch, South Africa, 8Institute for Aging Research, Hebrew Senior Life, Harvard Medical School, Boston, MA, 9University of Hong Kong, Pokfulam, Hong Kong, China, 10Bangalore Diabetes Centre, Bangalore, India, 11Yonsei University, Seoul, South Korea, 12Peking Union Medical College Hospital, Beijing, China, 13Bern University Hospital, Bern, Switzerland, 14Centro de Osteopatías Médicas, Buenos Aires, Argentina, 15University of Occupational & Environmental Health, Fukuoaka, Japan, 16CHU-Centre Ville, Policliniques BRULL, Liege, Belgium, 17Department of Medicine, University of Auckland, Auckland, New Zealand, 18Pontificia Universidad Católica de Chile, Santiago, Chile, 19Paris Descartes University, Cochin Hospital, Paris, France, 20Bone Metabolism Clinic, Hospital Angeles del Pedregal, Mexico City, Mexico, 21Mercy Health Osteoporosis and Bone Health Services, Cincinnati, OH, 22IDIM Instituto de Investigaciones Metabolicas, Buenos Aires, Argentina, 23Centro Paulista de Investigações Clinicas, São Paulo, Brazil, 24Merck Sharp and Dohme Corp., Rahway, NJ, 25MSD Europe Inc., Brussels, Belgium, 26Clinical Research, Merck Sharp and Dohme Corp., Rahway, NJ

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: , ,

Session Information

Title: Osteoporosis and Metabolic Bone Disease - Clinical Aspects and Pathogenesis: Osteoporosis: Treatment, Safety, and Long Term Outcomes

Session Type: Abstract Submissions (ACR)

Background/Purpose: Odanacatib (ODN), a selective oral inhibitor of cathepsin K, is in development for the treatment of osteoporosis. The Phase III Long-Term Odanacatib Fracture Trial (LOFT; NCT00529373) and its pre-planned blinded extension in which patients continue on their originally assigned treatment, evaluated the efficacy and safety of ODN in reducing the risk of fractures in postmenopausal women with osteoporosis.

Methods: This randomized, double-blind, placebo-controlled, event-driven study enrolled women ≥65 years of age with a BMD T-score ≤−2.5 at the total hip (TH) or femoral neck (FN) or with a radiographic vertebral fracture (VFx) and a T-score ≤−1.5 at the TH or FN. Participants were randomized to either ODN 50 mg once-weekly or placebo (1:1) and received weekly vitamin D3(5600IU) and daily calcium supplements to ensure a total daily calcium intake of ~1200 mg. Primary efficacy endpoints of the trial were new morphometric vertebral, clinical hip, and clinical non-vertebral fractures. Secondary endpoints included safety and tolerability, clinical VFx, spine and hip BMD, and bone turnover markers.

Results: A total of 16,713 participants were randomized at 387 centers in 40 countries, with 16,071 included in the analyses, and 642 excluded from all analyses due to study site closure (n=483), duplicate randomization (n=3), or failure to take any study drug (n=156). At baseline, mean (SD) age was 72.8 (5.3) years, 57% were Caucasian, 46.5% had a VFx prior to study entry, and mean BMD T-scores were: lumbar spine -2.7, TH -2.4, and FN -2.7. A total of 237 patients with hip fracture were estimated to provide statistical power. A prespecified interim analysis was performed when ~70% of targeted events had accrued. An external Data Monitoring Committee (DMC) reviewed these data and recommended that the base study be closed early due to robust efficacy and a favorable benefit/risk profile. The DMC noted that safety issues remained in certain selected areas. Both safety and efficacy continue to be monitored in the ongoing blinded extension trial. Data from an average follow-up of 40.8 months have been accrued from the base and extension studies, with 7,081 patients completing at least 4 years of follow-up. At the time this abstract was written, final data analyses were not complete.

Conclusion: The blinded, placebo-controlled base and extension study periods of LOFT will provide data on the efficacy of ODN on fractures and BMD and general safety. A separate presentation will discuss in depth the safety profile for ODN from this trial.

Disclosure:

M. R. McClung,

Amgen, Lilly, Merck,

5,

Amgen, Merck,

2,

Amgen, Merck, Warner-Chilcot,

7;

B. Langdahl,

Merck, Amgen, Lilly,

5,

Amgen, Lilly, Merck,

2,

Merck, Amgen, Lilly,

8;

S. Papapoulos,

Merck, Amgen, GSK, Novartis, Axsome,

5;

K. G. Saag,

Amgen, Merck,

2,

Amgen, Lilly, Merck,

5;

S. Adami,

Amgen, Eli-Lilly, Abiogen, Roche, Merck,

5;

H. G. Bone,

Merck, Amgen,

2,

Merck, Amgen, Novartis,

5,

Amgen,

8;

T. de Villiers,

Merck, Amgen,

5,

Pfizer Inc,

8;

D. P. Kiel,

Merck, Lilly, Amgen, Novartis,

5,

Kluwer Wolter,

7;

A. Kung,
None;

P. Kumar,
None;

S. K. Lim,
None;

X. Ling,

Merck Pharmaceuticals,

2,

Merck Pharmaceuticals,

8;

K. Lippuner,

Amgen, Lilly, MSD, Takeda, UCB,

5;

C. Mautalen,

Merck, Servier,

5;

T. Nakamura,

MSD, Amgen,Asahi-Kasei, Chugai,

5;

J. Y. Reginster,

Servier, Novartis, Negma, Lilly, Wyeth, Amgen, GlaxoSmithKline, Roche, Merckle, Nycomed-Takeda, NPS, IBSA-Genevrier, Theramex, UCB, Asahi Kasei, Endocyte,

5,

Merck Sharp and Dohme, Lilly, Rottapharm, IBSA, Genevrier, Novartis, Servier, Roche, GlaxoSmithKline, Merckle, Teijin, Teva, Analis, Theramex, Nycomed, NovoNordisk, Ebewee Pharma, Zodiac, Danone, Will Pharma, Amgen,

9,

Bristol Myers Squibb, Merck Sharp & Dohme, Rottapharm, Teva, Roche, Amgen, Lilly, Novartis, GlaxoSmithKline, Servier, Pfizer, Theramex, Danone, Organon, Therabel, Boehringer, Chiltern, Galapagos,

2;

I. R. Reid,

Amgen, Merck, Novartis,

2,

Lilly, Merck, Novartis,

5;

J. A. Rodríguez-Portales,

Merck Pharmaceuticals,

2,

Merck Pharmaceuticals,

5;

C. Roux,
None;

J. Walliser,
None;

N. B. Watts,

OsteoDynamics,

1,

AbbVie, Amarin, Amgen Inc., Bristol-Meyers Squibb, Corcept, Endo, Imagepace, Janssen, Lilly, Merck, Novartis, Noven, Pfizer/Wyeth, Radius, Sanofi-aventis,

5,

Merck, NPS,

2,

Amgen Inc., Merck,

9;

J. R. Zanchetta,

Merck Pharmaceuticals,

5,

GSK,

8;

C. A. F. Zerbini,

Merck, Lilly, Amgen, Pfizer, Novartis, Roche,

2,

Merck, Lilly ,

5,

Merck, Pfizer,

8;

A. Rybak-Feiglin,

Merck Sharp and Dohme Corp.,

3;

D. Cohn,

Merck Sharp and Dohme Corp.,

3;

C. A. DaSilva,

Merck Sharp and Dohme Corp.,

3;

R. Massaad,

MSD Europe Inc.,

3;

A. Santora,

Merck Sharp and Dohme Corp.,

3;

B. B. Scott,

Merck Sharp and Dohme Corp.,

3;

N. Verbruggen,

MSD Europe Inc.,

3;

A. Leung,

Merck Sharp and Dohme Corp.,

3;

A. Lombardi,

Merck Sharp and Dohme Corp.,

3.

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