Spotlight on denosumab in postmenopausal osteoporosis.

Denosumab (Prolia®) is a human recombinant monoclonal antibody that is approved for the treatment of postmenopausal osteoporosis in women at high or increased risk of fracture in the US, the EU, and several other countries. Denosumab has a novel mechanism of action; it binds to receptor activator of nuclear factor κB ligand and inhibits bone resorption by inhibiting osteoclast formation, function, and survival. In postmenopausal women with osteoporosis, denosumab reduced the risk of vertebral, nonvertebral, and hip fractures compared with placebo over 3 years in the large, phase III FREEDOM study. In postmenopausal women with low bone mineral density (BMD) or osteoporosis, treatment with denosumab increased BMD and decreased markers of bone turnover more than alendronate in those who were essentially treatment-naive in the 1-year DECIDE study and also in the 1-year STAND study, in which women were switched from alendronate to denosumab or continued alendronate treatment. Denosumab was generally well tolerated in clinical trials, although long-term effects of very low bone turnover remain to be established. Denosumab is administered once every 6 months via subcutaneous injection, which may be a preferred method of administration and may improve adherence to treatment compared with other osteoporosis treatments. Denosumab is a valuable new option for the treatment of postmenopausal osteoporosis in women at increased or high risk of fractures, and may be useful as a first-line treatment in women at increased risk of fractures who are unable to take other osteoporosis treatments.

The role and efficacy of denosumab in the treatment of osteoporosis: an update.

INTRODUCTION: Bone strength determinants such as bone mineral density and bone quality parameters are determined by life-long remodeling of skeletal tissue. Denosumab is a fully human mAb receptor activator of NF-κB ligand, which selectively inhibits osteoclastogenesis, the end product of a cascade interaction among numerous systemic and local factors and osteoblasts. It has been approved for clinical use by the FDA in the US and by the European Medicines Agency in Europe since June 2010 (trade name Prolia(™), Amgen, Thousand Oaks, CA, USA). AREAS COVERED: This review establishes the concerns and provides insights in issues concerning the cost-effectiveness and safety profile of this new pharmaceutical agent. There is an effort to clarify the special characteristics and the anti-catabolic role of denosumab in the bone tissue homeostasis and more specifically its potential clinical applications and clinical results in the field of postmenopausal osteoporosis. EXPERT OPINION: Administrated as a subcutaneous injection every 6 months, denosumab has been shown to decrease bone turnover and increase bone mineral density in postmenopausal women with low bone mass or osteoporosis and reduce vertebral, hip and nonvertebral fracture risk in postmenopausal women with osteoporosis. The rapid, sustained and reversible effect in suppressing osteoclastic bone resorption, the return of responsiveness on rechallenge, its good tolerability and ease of administration are features that distinguish it from other antiresorptive therapies.

Cost-effectiveness of Denosumab for the treatment of postmenopausal osteoporosis.

UNLABELLED: Denosumab is an injectable drug that reduces the risk of fractures. The objective was to estimate the cost-effectiveness of denosumab in a Swedish setting, also accounting for poor adherence to treatment. Denosumab is cost-effective, particularly for patients at high risk of fracture and low adherence to oral treatments. INTRODUCTION: Denosumab is a novel biologic agent developed for the treatment of osteoporosis and osteoporotic fractures that has been shown to reduce the risk of fractures in a phase III trial. The objective of this study was to estimate the cost-effectiveness of denosumab from a societal perspective compared with generic alendronate, branded risedronate, strontium ranelate, and no treatment in a Swedish setting. METHODS: A Markov cohort model was used to estimate the cost-effectiveness of denosumab given for up to 5 years to a typical Swedish patient population (women aged 71 years, T-score ≤ -2.5 SD and a prevalence of morphometric vertebral fractures of 34%). The model included treatment persistence and residual effect after discontinuation assumed to be equal to the time on treatment. Persistence with the comparator treatments and with denosumab was derived from prescription data and a persistence study, respectively. RESULTS: The base-case incremental cost-effectiveness ratios were estimated at €27,000, €12,000, €5,000, and €14,000, for denosumab compared with generic alendronate, risedronate, strontium ranelate, and no treatment, respectively. Sub-optimal persistence had the greatest impact in the comparison with generic alendronate, where the difference in drug cost was large. CONCLUSION: Improving persistence with osteoporosis treatment impacts positively on cost-effectiveness with a larger number of fractures avoided in the population targeted for treatment. Denosumab is a cost-effective alternative to oral osteoporosis treatments, particularly for patients at high risk of fracture and low expected adherence to oral treatments.

Injection of hope.

A new drug or the prevention of osteoporosis is both effective and convenient, only requiring an injection every six months.

Potential cost-effectiveness of denosumab for the treatment of postmenopausal osteoporotic women.

Denosumab has recently been shown to be safe and to significantly reduce the risk of vertebral, hip and non-vertebral fractures in the "Fracture REduction Evaluation of Denosumab in Osteoporosis every 6Months" (FREEDOM) Trial. Besides the clinical profile of a new drug, it becomes increasingly important to assess whether the drug represents good value for money. This study aims to examine the potential cost-effectiveness of denosumab in the treatment of postmenopausal osteoporotic women. An updated version of a validated Markov microsimulation model was used to estimate the cost (euro2009) per quality-adjusted life-year (QALY) gained of a 3-year denosumab treatment compared with no treatment. The model was populated with cost and epidemiological data for Belgium from a health-care perspective and the base-case population was defined from the FREEDOM Trial. The effect of denosumab after treatment cessation was conservatively assumed to decline linearly over 1year. Uncertainty was investigated using one-way and probabilistic sensitivity analyses. In particular, additional analyses were performed in populations (over 60 years) where osteoporosis medications are currently reimbursed in many European countries, i.e. with bone mineral density (BMD) T-score < or = -2.5 or prevalent vertebral fracture. In the base-case analysis, the cost per QALY gained of denosumab compared with no treatment was estimated at euro28,441. This value decreased to euro15,532 and to euro11,603 for women with a BMD T-score of -2.5 or prevalent vertebral fracture, respectively. Additional analyses showed that the cost-effectiveness of denosumab fall below commonly accepted threshold of euro 30,000per QALY gained for women with a BMD T-score < or = -2.5 or prevalent vertebral fracture, over the entire age range examined (60-80 years). The results were robust under a wide range of plausible assumptions. In conclusion, this study suggests, on the basis of currently available data, that denosumab is cost-effective compared with no treatment for postmenopausal Belgian women with low bone mass and who are similar to patients included in the FREEDOM Trial. In addition, denosumab was found to be cost-effective in population currently reimbursed in Europe with T-score < or = -2.5 or prevalent vertebral fracture, aged 60 years and above. Additional data are needed on the relative cost-effectiveness compared with other anti-osteoporotic agents and on the long-term safety of denosumab.

[From orthoclone to denosumab, the fast growing market of monoclonal antibodies]. / D'orthoclone au dénosumab : l'expansion des anticorps monoclonaux à des fins thérapeutiques.

Monoclonal antibodies are a specific medicinal category within the current therapeutic armamentarium. Their market share is growing fast as they are often the only therapeutic option at some stages of certain diseases, due to their targeted action in the body and to an acceptable tolerance. The budget impact of monoclonal antibodies is increasing, leading payers and health authorities to growing attention and pressure when they have to decide on the reimbursement, coverage and pricing of these products. The launch of biosimilars after patent expiry of some of these drugs will take time in view of the complexity of these molecules, and is not likely to significantly impact the cost of these therapies.