Profile of romosozumab and its potential in the management of osteoporosis

Lim, Sian Yik; Bolster, Marcy B.

doi:10.2147/dddt.s127568

Cited by 78 publications

(61 citation statements)

References 46 publications

(79 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…50,51 Preclinical data corroborated the proof-of-concept that absence of sclerostin or inhibition with monoclonal antibodies enhanced bone strength and conferred resistance to bone fractures. 52 Thus, several sclerostin antibodies, including romosozumab (AMG-785) 53 and BPS804, 54 are being clinically evaluated, the evaluation of romosozumab being most advanced (table 2). In a phase 2 study of romosozumab versus placebo, alendronate, and teriparatide in 419 postmenopausal women, 55 romosozumab for 12 months increased BMD at the lumbar spine and the hip.…”

Section: New Drugs On the Horizonmentioning

confidence: 99%

Osteoporosis treatment: recent developments and ongoing challenges

Khosla

Hofbauer

2017

The Lancet Diabetes & Endocrinology

688

498

View full text Add to dashboard Cite

Osteoporosis is an enormous and growing public health problem. Once considered an inevitable consequence of ageing, it is now eminently preventable and treatable. Ironically, despite tremendous therapeutic advances, there is an increasing treatment gap for patients at high fracture risk. In this Series paper, we trace the evolution of drug therapy for osteoporosis, which began in the 1940s with the demonstration by Fuller Albright that treatment with oestrogen could reverse the negative calcium balance that developed in women after menopause or oophorectomy. We note a watershed in osteoporosis drug discovery around the year 2000, when the approach to developing novel therapeutics shifted from one driven by discoveries in animal studies and clinical observations (eg, oestrogen, calcitonin, and teriparatide) or opportunistic repurposing of existing compounds (eg, bisphosphonates) to one driven by advances in fundamental bone biology (eg, denosumab) coupled with clues from patients with rare bone diseases (eg, romosozumab, odanacatib). Despite these remarkable advances, concerns about rare side-effects of anti-resorptive drugs, particularly bisphosphonates, and the absence of clear evidence in support of their long-term efficacy is leading many patients who could benefit from drug therapy to not take these drugs. As such, there remains an important clinical need to develop ways to enhance patient acceptance and compliance with these effective drugs, and to continue to develop new drugs that do not cause these side-effects and have prolonged anabolic effects on bone. Such changes could lead to a true reversal of this potentially devastating disease of ageing.

show abstract

Section: New Drugs On the Horizonmentioning

confidence: 99%

Osteoporosis treatment: recent developments and ongoing challenges

Khosla

Hofbauer

2017

The Lancet Diabetes & Endocrinology

688

498

View full text Add to dashboard Cite

show abstract

“…After 1 year, the markers suggest that the drug's actions have been converted essentially to the behaviour of a pure antiresorptive. With this is mind, it was prescient to design FRAME and ARCH to be a 1‐year‐only exposure to romosozumab, which corresponds to the period when it is acting as an osteoanabolic and antiresorptive agent together (Figure ) .…”

Section: Dual Actions Drug: Romosozumabmentioning

confidence: 99%

Osteoanabolic and dual action drugs

Tabacco

Bilezikian

2019

Brit J Clinical Pharma

View full text Add to dashboard Cite

Teriparatide (TPTD) and Abaloparatide (ABL) are the only osteoanabolic drugs available, at this time, for treatment of osteoporosis. TPTD is a 34-amino acid fragment that is identical in its primary sequence to the 34 amino acids of full-length human parathyroid hormone [hPTH(1-84)]. ABL is identical to parathyroid hormone related peptide (PTHrP) through the first 22 residues with significantly different amino acids inserted thereafter, between residues 22 and 34. The osteoanabolic actions of PTH are due directly to its effects on cells of the osteoblast lineage and indirectly by stimulating IGF-I synthesis and suppressing sclerostin and associated enhancement of Wnt signaling. Both TPTD and ABL are ligands that bind to and activate the PTH receptor type 1 (PTHR1) receptor but they appear to do so differently: ABL favors the transient, more anabolic configuration of the receptor. Both TPTD and ABL reduce the risk of vertebral fractures and non-vertebral fractures. Both drugs are administered for a maximum of 24 months, and should be followed by an anti-resorptive agent to maintain gains in BMD. Romosozumab, a monoclonal antibody that binds to and inhibits sclerostin, appears to have dual actions by stimulating bone formation and reducing bone resorption. In the pivotal clinical trial, romosozumab, administered as a 210 mg monthly subcutaneous dose, significantly reduced new vertebral fractures and in a subsequent study reduced both vertebral and non-vertebral fractures.

show abstract

“…Animal studies with romosozumab in ovariectomized rats and primates showed increases in bone mass and strength owing to the increased bone formation and reduced resorption [104,105]. Early human trials of romosozumab showed that the agent reaches peak serum concentration within a week, demonstrating a high binding affinity for sclerostin while displaying non-linear kinetics with biphasic elimination (t1/2=11-18 and 6-7 days) [106][107][108].…”

Section: Emerging Therapies 231 Anabolic Agents With Antiresorptivementioning

confidence: 99%

Current and emerging osteoporosis pharmacotherapy for women: state of the art therapies for preventing bone loss

Fontalis

Kenanidis

Kotronias

et al. 2019

Expert Opinion on Pharmacotherapy

View full text Add to dashboard Cite

Introduction: Pharmacological options to address the imbalance between bone resorption and accrual in osteoporosis include anti-resorptive and osteoanabolic agents. Unique biologic pathways such as Wnt/-catenin pathway have been targeted in the quest for new emerging therapeutic strategies. Areas Covered: This review aims to provide an overview of existing pharmacotherapy for osteoporosis in women and explore state-of-the-art and emerging therapies to prevent bone loss, with an emphasis on the mechanism of action, indications and side effects. Expert Opinion: Bisphosphonates appear to be a reliable and cost-effective option, whereas denosumab has introduced a simpler dosing regimen and may achieve a linear increase in BMD with no plateau being observed, along with continuous anti-fracture efficacy. Selective estrogen receptor modulators (SERMs) are synthetic non-steroidal agents which have varying estrogen agonist and antagonist activities in different tissues and antifracture efficacy. Abaloparatide, a parathyroid-hormone-related peptide (PTHrP)-analogue, approved by the FDA in April 2017, constitutes the first new anabolic osteoporosis drug in the US for nearly 15 years and has also proven its anti-fracture efficacy. Romosozumab, a sclerostin inhibitor, which induces bone formation and suppresses bone resorption, has also been developed and shown anti-fracture efficacy; however, concerns have arisen with regard to increased cardiovascular risk.

show abstract

Profile of romosozumab and its potential in the management of osteoporosis

Cited by 78 publications

References 46 publications

Osteoporosis treatment: recent developments and ongoing challenges

Osteoporosis treatment: recent developments and ongoing challenges

Osteoanabolic and dual action drugs

Current and emerging osteoporosis pharmacotherapy for women: state of the art therapies for preventing bone loss

Contact Info

Product

Resources

About