Romosozumab

Identification

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Name
Romosozumab
Accession Number
DB11866
Type
Biotech
Groups
Approved, Investigational
Biologic Classification
Protein Based Therapies
Monoclonal antibody (mAb)
Description

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 therapiesLabel. 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 study7,8. 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.

Protein chemical formula
Not Available
Protein average weight
145805.0 Da
Sequences
Not Available
Synonyms
  • romosozumab-aqqg
External IDs
Amg 785
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
EvenitySolution105 mgSubcutaneousAmgenNot applicableNot applicableCanada
EvenityInjection, solution105 mg/1.17mLSubcutaneousAMGEN INC2019-04-09Not applicableUs
Additional Data Available
  • Application Number
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  • Product Code
    Product Code

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Categories
UNII
3VHF2ZD92J
CAS number
909395-70-6

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 treatmentsLabel.

Associated Conditions
Pharmacodynamics

Romosozumab is a subcutaneously injected humanized monoclonal antibody that inhibits the secreted protein sclerostinLabel. 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 osteoclasts1,2.

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 61,2. 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 resorption1,2. Both effects from the same therapy have not been seen in other osteoporosis treatments to date1.

TargetActionsOrganism
ASclerostin
inhibitor
Humans
Additional Data Available
Adverse Effects

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Contraindications

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Blackbox Warnings

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Absorption

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

Volume of distribution

3.92LLabel.

Protein binding

Monoclonal antibodies are generally not protein bound5,6. In about 10%2 to 18.1%Label of cases patients develop antibodies against romosozumab. 4.7% of the patients developed neutralizing antibodiesLabel. The presence of antibodies against romosozumab can reduce the availability of romosozumab by 22%, and 63% in the case of neutralizing antibodiesLabel.

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 drugsLabel.

Route of elimination

Monoclonal antibodies are eventually phagocytosed and broken down to smaller peptides and amino acidsLabel which are eliminated in a similar fashion to other proteins5,6.

Half life

12.8 daysLabel.

Clearance

0.38mL/hr/kgLabel.

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 impairmentLabel. However, patients with severe renal impairment or who are on dialysis are at an increased risk of hypocalcemiaLabel. A patient's weight will affect their level of romosozumab exposureLabel.

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

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

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.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AbciximabThe risk or severity of adverse effects can be increased when Abciximab is combined with Romosozumab.
AbituzumabThe risk or severity of adverse effects can be increased when Romosozumab is combined with Abituzumab.
AbrilumabThe risk or severity of adverse effects can be increased when Romosozumab is combined with Abrilumab.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Romosozumab.
AdecatumumabThe risk or severity of adverse effects can be increased when Adecatumumab is combined with Romosozumab.
AducanumabThe risk or severity of adverse effects can be increased when Romosozumab is combined with Aducanumab.
AfelimomabThe risk or severity of adverse effects can be increased when Afelimomab is combined with Romosozumab.
AlemtuzumabThe risk or severity of adverse effects can be increased when Alemtuzumab is combined with Romosozumab.
AlirocumabThe risk or severity of adverse effects can be increased when Alirocumab is combined with Romosozumab.
AmatuximabThe risk or severity of adverse effects can be increased when Romosozumab is combined with Amatuximab.
Additional Data Available
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  • Severity
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  • Action
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Food Interactions
Not Available

References

General References
  1. 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. [PubMed:20593411]
  2. 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. [PubMed:29942362]
  3. 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. [PubMed:28892457]
  4. 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. [PubMed:28755782]
  5. 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. [PubMed:16478695]
  6. Lobo ED, Hansen RJ, Balthasar JP: Antibody pharmacokinetics and pharmacodynamics. J Pharm Sci. 2004 Nov;93(11):2645-68. doi: 10.1002/jps.20178. [PubMed:15389672]
  7. Romosozumab FDA Approval Announcement [Link]
  8. FDA Meeting Of The Bone, Reproductive and Urologic Drugs Advisory Committee For Rosozumab [Link]
External Links
PubChem Substance
347911253
Wikipedia
Romosozumab
ATC Codes
M05BX06 — Romosozumab
FDA label
Download (436 KB)
MSDS
Download (36 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentOsteopenia3
1CompletedTreatmentOne to five years postmenopausal / Osteopenia1
1CompletedTreatmentOsteoporosis1
1CompletedTreatmentOsteoporosis / Postmenopausal Osteoporosis (PMO)1
2CompletedTreatmentFracture Healing2
2CompletedTreatmentLow Bone Mineral Density / Postmenopausal Osteoporosis (PMO)1
2CompletedTreatmentPostmenopausal Osteoporosis (PMO)1
3CompletedTreatmentOsteoporosis in Men1
3CompletedTreatmentPostmenopausal Osteoporosis (PMO)4
3CompletedTreatmentPostmenopausal Women With Osteoporosis1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Injection, solutionSubcutaneous105 mg/1.17mL
SolutionSubcutaneous105 mg
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available

Taxonomy

Description
Not Available
Kingdom
Organic Compounds
Super Class
Organic Acids
Class
Carboxylic Acids and Derivatives
Sub Class
Amino Acids, Peptides, and Analogues
Direct Parent
Peptides
Alternative Parents
Not Available
Substituents
Not Available
Molecular Framework
Not Available
External Descriptors
Not Available

Targets

1. Sclerostin
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
References
  1. 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. [PubMed:28755782]
  2. FDA Meeting Of The Bone, Reproductive and Urologic Drugs Advisory Committee For Rosozumab [Link]
  3. Romosozumab FDA Approval Announcement [Link]
  4. Romosozumab FDA Label [File]

Drug created on October 20, 2016 14:55 / Updated on July 13, 2019 00:57