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 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.

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
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Treatment ofOsteoporosis•••••••••••••••••••••••••••••••••••
Treatment ofOsteoporosis••••••••••••••••••• •• ••••• ••••••• ••• •••••••••••••••••••••
Treatment ofOsteoporosis•••••••••••••••••••••
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 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
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 bound5,6. 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 proteins5,6.

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.
DrugInteraction
AbciximabThe risk or severity of adverse effects can be increased when Abciximab is combined with Romosozumab.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Romosozumab.
AducanumabThe risk or severity of adverse effects can be increased when Romosozumab is combined with Aducanumab.
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.
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
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
EvenityInjection, solution105 mgSubcutaneousUcb Pharma S.A.2020-12-16Not applicableEU flag
EvenityInjection, solution105 mgSubcutaneousUcb Pharma S.A.2020-12-16Not applicableEU flag
EvenityInjection, solution105 mgSubcutaneousUcb Pharma S.A.2020-12-16Not applicableEU flag
EvenitySolution105 mg / 1.17 mLSubcutaneousAmgen2019-08-12Not applicableCanada flag
EvenityInjection, solution105 mgSubcutaneousUcb Pharma S.A.2020-12-16Not applicableEU flag

Categories

ATC Codes
M05BX06 — Romosozumab
Drug Categories
Chemical TaxonomyProvided by Classyfire
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
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
3VHF2ZD92J
CAS number
909395-70-6

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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  7. Romosozumab FDA Approval Announcement [Link]
  8. FDA Meeting Of The Bone, Reproductive and Urologic Drugs Advisory Committee For Rosozumab [Link]
  9. FDA Approved Drug Products: EVENITY (romosozumab-aqqg) injection, for subcutaneous use [Link]
PubChem Substance
347911253
RxNav
2123180
Wikipedia
Romosozumab
FDA label
Download (436 KB)
MSDS
Download (36 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingPreventionOsteoporosis / Spinal Cord Injuries1
4Active Not RecruitingTreatmentPostmenopausal Osteoporosis1
4CompletedTreatmentOsteoporosis caused by Glucocorticoid Treatment1
4Not Yet RecruitingTreatmentOsteoporosis Fracture / Spinal Cord Injuries1
4RecruitingPreventionOsteoporosis / Spinal Cord Injuries1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Injection, solutionSubcutaneous105 mg/1.17mL
Injection, solutionSubcutaneous105 MG
SolutionSubcutaneous105 mg / 1.17 mL
SolutionSubcutaneous105.000 mg
SolutionSubcutaneous105 MG/1.17ML
SolutionSubcutaneous90 mg
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available

Targets

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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
  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. [Article]
  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 at October 20, 2016 20:55 / Updated at June 03, 2022 07:24