Romosozumab

Identification

Summary

Romosozumab is a monoclonal antibody used to treat osteoporosis in postmenopausal women at high risk of fracture, patients who are intolerant of other treatments, or patients who have failed other treatments.

Brand Names

Evenity 210 Mg Dose

Generic Name

Romosozumab

DrugBank Accession Number

DB11866

Background

Romosozumab is a humanized monoclonal antibody indicated for the treatment of osteoperosis in postmenopausal women at high risk of fracture and patients who have failed in other treatments or are intolerant to other osteoperosis therapies⁹. Romosozumab prevents bone resorption and induces the formation of bone though it is associated with an increased risk of cardiac death, heart attack, and stroke in one study^7,8. In a comparison study of post menopausal women with osteoporosis and a past fracture, romosozumab for 12 months followed by alendronic acid for 12 months was superior to alendronic acid alone for 24 months³. Romosozumab also demonstrates a faster and larger increase in bone density than teriparatide⁴. Romosozumab is marketed in the United States by Amgen under the brand name Evinity⁷. Romosozumab was granted FDA approval on April 9,2019⁷.

Type

Biotech

Groups

Approved, Investigational

Biologic Classification

Protein Based Therapies
Monoclonal antibody (mAb)

Protein Chemical Formula

Not Available

Protein Average Weight

145805.0 Da

Sequences

Not Available

Synonyms

Romosozumab
romosozumab-aqqg

External IDs

Amg 785

Pharmacology

Indication

Romosozumab is indicated for the treatment of osteoporosis in post menopausal women at high risk of fractures and also in patients with osteoperosis who are intolerant to other treatments or who have failed in other treatments⁹.

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Associated Conditions

Osteoporosis

Contraindications & Blackbox Warnings

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Pharmacodynamics

Romosozumab is a subcutaneously injected humanized monoclonal antibody that inhibits the secreted protein sclerostin⁹. Inhibition of this protein allows Wnt signalling in osteoblasts to promote bone formation and allows for the inhibition of receptor activator of nuclear factor kappa-beta-ligand (RANKL) mediated bone resorption by osteoclasts^1,2.

Mechanism of action

Osteocytes secrete sclerostin which inhibits bone formation by binding to low-density lipoprotein (LDL) receptor-related proteins 5 and 6 of osteoblasts, inhibiting the Wnt signal pathway¹.

Romosozumab targets and inhibits the protein sclerostin, thereby preventing inhibition of bone formation by allowing Wnt to bind to LDL receptor-related proteins 5 and 6^1,2. Activation of the Wnt pathways leads to downstream signalling, translocation of beta catenin to the osteoblast nucleus where it promotes survival and proliferation of osteoblasts².

Sclerostin also promotes bone resorption through increasing production of receptor activator of nuclear factor kappa-beta-ligand (RANKL)².

Romosozumab's inhibition of sclerostin also inhibits the increase in RANKL dependant increases in osteoclast activity and bone resorption^1,2. Both effects from the same therapy have not been seen in other osteoporosis treatments to date¹.

Target	Actions	Organism
ASclerostin	inhibitor	Humans

Absorption

Romosozumab reaches peak concentration within 2 to 7 days with a median time of 5 days⁹. Subcutaneous bioavailability is 50 to 70%^1,2.

Volume of distribution

3.92L⁹.

Protein binding

Monoclonal antibodies are generally not protein bound^5,6. In about 10%² to 18.1%⁹ of cases patients develop antibodies against romosozumab. 4.7% of the patients developed neutralizing antibodies⁹. The presence of antibodies against romosozumab can reduce the availability of romosozumab by 22%, and 63% in the case of neutralizing antibodies⁹.

Metabolism

The metabolism of romosozumab has not been clarified, however it is expected to be degraded into small peptides and amino acids like other protein drugs⁹.

Route of elimination

Monoclonal antibodies are eventually phagocytosed and broken down to smaller peptides and amino acids⁹ which are eliminated in a similar fashion to other proteins^5,6.

Half-life

12.8 days⁹.

Clearance

0.38mL/hr/kg⁹.

Adverse Effects

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Toxicity

There are no significant differences in pharmacokinetics cross age, sex, race, progression of osteoporosis, past history of alendronic acid prescribing, and all stages of renal impairment⁹. However, patients with severe renal impairment or who are on dialysis are at an increased risk of hypocalcemia⁹. A patient's weight will affect their level of romosozumab exposure⁹.

Romosozumab has not been shown to be associated with carcinogenicity or impairment of fertility, and is not expected to be mutagenic⁹.

Romosozumab is not indicated in pregnancy, lactation, or pedatric patients⁹. Romosozumab is associated with skeletal defects in the offspring of rats given romosozumab and is detected in the excreted milk⁹.

Romosozumab is currently undergoing post marketing surveillance to ensure the risk of major adverse cardiac events is not being underestimated⁸. There is currently an expected hazard ratio of 1.30 compared to current treatments for osteoporosis, though hip and vertebral fractures may have an equal impact on overall quality of life⁸.

Pathways

Not Available

Pharmacogenomic Effects/ADRs

Not Available

Interactions

Drug Interactions

This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

Drug	Interaction
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Abciximab	The risk or severity of adverse effects can be increased when Abciximab is combined with Romosozumab.
Adalimumab	The risk or severity of adverse effects can be increased when Adalimumab is combined with Romosozumab.
Aducanumab	The risk or severity of adverse effects can be increased when Romosozumab is combined with Aducanumab.
Alemtuzumab	The risk or severity of adverse effects can be increased when Alemtuzumab is combined with Romosozumab.
Alirocumab	The risk or severity of adverse effects can be increased when Alirocumab is combined with Romosozumab.
Amivantamab	The risk or severity of adverse effects can be increased when Romosozumab is combined with Amivantamab.
Anifrolumab	The risk or severity of adverse effects can be increased when Romosozumab is combined with Anifrolumab.
Ansuvimab	The risk or severity of adverse effects can be increased when Romosozumab is combined with Ansuvimab.
Anthrax immune globulin human	The risk or severity of adverse effects can be increased when Anthrax immune globulin human is combined with Romosozumab.
Antilymphocyte immunoglobulin (horse)	The risk or severity of adverse effects can be increased when Antilymphocyte immunoglobulin (horse) is combined with Romosozumab.

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Food Interactions

Administer calcium supplement. Ensure adequate calcium supplementation.
Administer vitamin supplements. Ensure adequate vitamin D supplementation.

Products

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Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End
Evenity	Injection, solution	105 mg	Subcutaneous	Ucb Pharma S.A.	2020-12-16	Not applicable
Evenity	Injection, solution	105 mg	Subcutaneous	Ucb Pharma S.A.	2020-12-16	Not applicable
Evenity	Solution	105 mg / 1.17 mL	Subcutaneous	Amgen	2019-08-12	Not applicable
Evenity	Injection, solution	105 mg	Subcutaneous	Ucb Pharma S.A.	2020-12-16	Not applicable
Evenity	Injection, solution	105 mg	Subcutaneous	Ucb Pharma S.A.	2020-12-16	Not applicable
Evenity	Injection, solution	105 mg/1.17mL	Subcutaneous	AMGEN INC	2019-04-09	Not applicable

Chemical Identifiers

UNII: 3VHF2ZD92J
CAS number: 909395-70-6

References

General References

Padhi D, Jang G, Stouch B, Fang L, Posvar E: Single-dose, placebo-controlled, randomized study of AMG 785, a sclerostin monoclonal antibody. J Bone Miner Res. 2011 Jan;26(1):19-26. doi: 10.1002/jbmr.173. [Article]
Solling ASK, Harslof T, Langdahl B: The clinical potential of romosozumab for the prevention of fractures in postmenopausal women with osteoporosis. Ther Adv Musculoskelet Dis. 2018 Jun;10(5-6):105-115. doi: 10.1177/1759720X18775936. Epub 2018 Jun 7. [Article]
Saag KG, Petersen J, Brandi ML, Karaplis AC, Lorentzon M, Thomas T, Maddox J, Fan M, Meisner PD, Grauer A: Romosozumab or Alendronate for Fracture Prevention in Women with Osteoporosis. N Engl J Med. 2017 Oct 12;377(15):1417-1427. doi: 10.1056/NEJMoa1708322. Epub 2017 Sep 11. [Article]
Langdahl BL, Libanati C, Crittenden DB, Bolognese MA, Brown JP, Daizadeh NS, Dokoupilova E, Engelke K, Finkelstein JS, Genant HK, Goemaere S, Hyldstrup L, Jodar-Gimeno E, Keaveny TM, Kendler D, Lakatos P, Maddox J, Malouf J, Massari FE, Molina JF, Ulla MR, Grauer A: Romosozumab (sclerostin monoclonal antibody) versus teriparatide in postmenopausal women with osteoporosis transitioning from oral bisphosphonate therapy: a randomised, open-label, phase 3 trial. Lancet. 2017 Sep 30;390(10102):1585-1594. doi: 10.1016/S0140-6736(17)31613-6. Epub 2017 Jul 26. [Article]
Tabrizi MA, Tseng CM, Roskos LK: Elimination mechanisms of therapeutic monoclonal antibodies. Drug Discov Today. 2006 Jan;11(1-2):81-8. doi: 10.1016/S1359-6446(05)03638-X. [Article]
Lobo ED, Hansen RJ, Balthasar JP: Antibody pharmacokinetics and pharmacodynamics. J Pharm Sci. 2004 Nov;93(11):2645-68. doi: 10.1002/jps.20178. [Article]
Romosozumab FDA Approval Announcement [Link]
FDA Meeting Of The Bone, Reproductive and Urologic Drugs Advisory Committee For Rosozumab [Link]
FDA Approved Drug Products: EVENITY (romosozumab-aqqg) injection, for subcutaneous use [Link]

External Links

PubChem Substance: 347911253
RxNav: 2123180
Wikipedia: Romosozumab

FDA label

Download (436 KB)

MSDS

Download (36 KB)

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
4	Active Not Recruiting	Treatment	Osteoporosis caused by Glucocorticoid Treatment	1
4	Active Not Recruiting	Treatment	Postmenopausal Osteoporosis	1
4	Not Yet Recruiting	Treatment	Osteoporosis Fracture / Spinal Cord Injuries	1
4	Recruiting	Prevention	Osteoporosis / Spinal Cord Injuries	2
4	Recruiting	Treatment	Osteoporosis / Osteoporosis Fracture / Postmenopausal Osteoporosis	1
3	Active Not Recruiting	Treatment	Osteoporosis	1
3	Completed	Treatment	Male Osteoporosis	1
3	Completed	Treatment	Postmenopausal Osteoporosis	6
3	Recruiting	Treatment	Anorexia Nervosa (AN) / Bone Loss / Eating Disorders / Low Bone Density	1
2	Active Not Recruiting	Treatment	Bone Loss / Chronic Spinal Paralysis / Osteoporosis / Osteoporosis, Osteopenia / Spinal Cord Injuries	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage Forms

Form	Route	Strength
Injection, solution	Subcutaneous	105 mg/1.17mL
Injection, solution	Subcutaneous	105 MG
Solution	Subcutaneous	105 mg / 1.17 mL
Solution	Subcutaneous	105 MG/1.17ML
Solution	Subcutaneous	90 mg

Prices

Not Available

Patents

Not Available

Properties

State: Solid
Experimental Properties: Not Available

Targets

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Details1. Sclerostin

Kind: Protein
Organism: Humans
Pharmacological action: Yes
Actions: Inhibitor

General Function: Negative regulator of bone growth that acts through inhibition of Wnt signaling and bone formation.
Specific Function: Heparin binding
Gene Name: SOST
Uniprot ID: Q9BQB4
Uniprot Name: Sclerostin
Molecular Weight: 24030.31 Da

References

Langdahl BL, Libanati C, Crittenden DB, Bolognese MA, Brown JP, Daizadeh NS, Dokoupilova E, Engelke K, Finkelstein JS, Genant HK, Goemaere S, Hyldstrup L, Jodar-Gimeno E, Keaveny TM, Kendler D, Lakatos P, Maddox J, Malouf J, Massari FE, Molina JF, Ulla MR, Grauer A: Romosozumab (sclerostin monoclonal antibody) versus teriparatide in postmenopausal women with osteoporosis transitioning from oral bisphosphonate therapy: a randomised, open-label, phase 3 trial. Lancet. 2017 Sep 30;390(10102):1585-1594. doi: 10.1016/S0140-6736(17)31613-6. Epub 2017 Jul 26. [Article]
FDA Meeting Of The Bone, Reproductive and Urologic Drugs Advisory Committee For Rosozumab [Link]
Romosozumab FDA Approval Announcement [Link]
Romosozumab FDA Label [File]

Drug created at October 20, 2016 20:55 / Updated at June 03, 2022 07:24

Romosozumab

Identification

Pharmacology

Interactions

Products

Categories

Chemical Identifiers

References

Clinical Trials

Pharmacoeconomics

Properties

Targets

References