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Identification
- Summary
Abaloparatide is a parathyroid hormone-related protein (PTHrP) analog used for the treatment of osteoporosis in patients with a high risk of fracture.
- Brand Names
- Tymlos
- Generic Name
- Abaloparatide
- DrugBank Accession Number
- DB05084
- Background
Abaloparatide is an N-terminal analog of parathyroid hormone-related protein (PTHrP) 4 and an agonist at the parathyroid hormone type 1 (PTH1) receptor.7 It is a synthetic 34 amino acid peptide with 41% homology to human parathyroid hormone 1-34 and human PTHrP 1-34.7 Abaloparatide and PTHrP share the first 21 amino acids and the receptor-activating domain.4
Abaloparatide is an osteoanabolic agent that stimulates bone formation.7 It was first approved by the FDA on April 28, 2017,1 for the treatment of osteoporosis in postmenopausal women and is also used to increase bone density in men with osteoporosis.7 In October 2022, the EMA's Committee for Medicinal Products for Human Use (CHMP) recommended abaloparatide be granted marketing authorization in Europe 8 and the drug was fully authorized by the European Commission on December 19, 2022.10
- Type
- Biotech
- Groups
- Approved, Investigational
- Biologic Classification
- Protein Based Therapies
Hormones - Protein Chemical Formula
- C174H300N56O49
- Protein Average Weight
- 3961.0 Da
- Sequences
>Abaloparatide N-terminal peptide sequence AVSEHQLLHDKGKSIQDLRRRELLEKLLXKLHTA
Download FASTA FormatReferences:
- FDA Approved Drug Products: TYMLOS (abaloparatide) injection, for subcutaneous use (December 2022) [Link]
- Synonyms
- Abaloparatide
- External IDs
- BA-058
- BA058
- BIM-44058
- BIM44058
Pharmacology
- Indication
Abaloparatide is indicated for the treatment of postmenopausal women with osteoporosis at high risk for fracture (defined as a history of osteoporotic fracture or multiple risk factors for fracture) 7,9 or patients who have failed or are intolerant to other available osteoporosis therapy.7 In postmenopausal women with osteoporosis, abaloparatide reduces the risk of vertebral and nonvertebral fractures.7
Abaloparatide is also indicated to increase bone density in men with osteoporosis at high risk for fracture (defined as a history of osteoporotic fracture or multiple risk factors for fracture) or patients who have failed or are intolerant to other available osteoporosis therapy.7
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Management of Osteoporosis •••••••••••• •••• •••• •• •••••••• ••••••••• Management of Osteoporosis •••••••••••• •••••• •••••••••••• ••••••• ••••••••• Management of Osteoporosis •••••••••••• ••••••••••• •••• •••••••••••• ••••••• ••••••••• Management of Osteoporosis •••••••••••• •••••••••••••• •••• •••• •• •••••••• ••••••••• Management of Osteoporosis •••••••••••• •••••••••••••• ••••••••••• •••• •••••••••••• ••••••• ••••••••• - Contraindications & Blackbox Warnings
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Abaloparatide stimulates bone formation on periosteal, trabecular, and cortical bone surfaces.2 It increases bone mineral density and bone formation markers in a dose-dependent manner.1,7 Abaloparatide causes transient and limited increases in osteoclast bone resorption and increases bone density.2,9 In rats and monkeys, abaloparatide exerted anabolic effects, increasing bone mineral density and mineral content correlating with increases in bone strength at vertebral and nonvertebral sites.7
- Mechanism of action
Abaloparatide is an agonist at the PTH1 receptor (PTH1R), a G-protein-coupled receptor (GPCR) that regulates bone formation and bone turnover, as well as mineral ion homeostasis.6 The PTH1R couples to Gs and Gq, which stimulates adenylyl cyclase (AC), which activates the cAMP/PKA signalling cascade, and phospholipase C (PLC), which activates the IP/PKC signalling cascade.4,6 Abaloparatide binds to the PTH1R in target cells to activate the Gs-protein-mediated cAMP signalling pathway, thereby stimulating osteoblastic activity.2,7 Abaloparatide also activates Gq and β-arrestin-1 pathway downstream of PTH1R as off-targets in target cells such as the testis and epididymis, which have been associated with anti-inflammatory effects and alleviation of epididymitis and orchitis symptoms.2,4,5
The PTH1R has two conformations with distinct ligand binding profiles. The R0 conformation is a G protein–independent high-affinity conformation, and upon binding, the ligand induces a longer-lasting signalling response that gradually increases cAMP. Due to the prolonged signalling response, ligands selectively binding to the R0 conformation are associated with a risk for increased calcium mobilization and hypercalcemia.3 Conversely, the RG conformation is G-protein–dependent (GTPγS-sensitive) with a shorter signalling response.3,4 Abaloparatide binds to the RG conformation with greater selectivity:3,2 it induces more transient signalling responses and favours net bone formation over bone resorption. The drug's relatively low risk for hypercalcemia and osteoclast resorption compared to teriparatide is attributed to the preferential binding of abaloparatide to the RG conformation.1,2
Target Actions Organism AParathyroid hormone/parathyroid hormone-related peptide receptor agonistHumans - Absorption
The absolute bioavailability of abaloparatide in healthy women after subcutaneous administration of an 80 mcg dose was 36%. Following subcutaneous administration of 80 mcg abaloparatide in postmenopausal women with osteoporosis for seven days, the mean (SD) Cmax was 812 (118) pg/mL and the AUC0-24 was 1622 (641) pgxhr/mL. The median Tmax was 0.51 hours, with a range from 0.25 to 0.52 hours.7
- Volume of distribution
The volume of distribution was approximately 50 L.7
- Protein binding
In vitro, abaloparatide was approximately 70% bound to plasma proteins.7
- Metabolism
Abaloparatide is metabolized into smaller peptide fragments via non-specific proteolytic degradation.7
- Route of elimination
The peptide fragments of abaloparatide are primarily eliminated through renal excretion.7
- Half-life
The mean half-life of abaloparatide is approximately one hour.7
- Clearance
The mean apparent total plasma clearance for subcutaneous administration is 168 L/h in healthy subjects.9
- Adverse Effects
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The LD50 in rats and mice following intravenous or subcutaneous administration was 42 mg/kg.11
One clinical study reported an accidental overdose in a patient who received 400 mcg in one day, which is five times the recommended clinical dose. This patient experienced asthenia, headache, nausea, and vertigo. Serum calcium was not assessed on the day of the overdose, but on the following day, the patient’s serum calcium was within the normal range. Other symptoms of overdose may include hypercalcemia, nausea, vomiting, dizziness, tachycardia, orthostatic hypotension, and headache. Since there is no specific antidote for abaloparatide overdose, it is recommended that overdose is managed with drug discontinuation, monitoring of serum calcium and phosphorus, and implementation of appropriate supportive measures, such as hydration. Based on the molecular weight, plasma protein binding and volume of distribution, abaloparatide is not expected to be dialyzable.7
- 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 Integrate drug-drug
interactions in your softwareAcebutolol The risk or severity of adverse effects can be increased when Acebutolol is combined with Abaloparatide. Aldesleukin The risk or severity of adverse effects can be increased when Aldesleukin is combined with Abaloparatide. Aliskiren The risk or severity of adverse effects can be increased when Abaloparatide is combined with Aliskiren. Ambrisentan Abaloparatide may increase the hypotensive activities of Ambrisentan. Amifostine The risk or severity of adverse effects can be increased when Amifostine is combined with Abaloparatide. - Food Interactions
- Administer vitamin supplements. If dietary intake is inadequate, patients should receive supplemental calcium and vitamin D.
- Take at the same time every day.
- Take with or without food.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Eladynos Injection, solution 80 μg/dose Subcutaneous Radius International Ltd 2024-07-10 2024-10-01 EU 
Eladynos Injection, solution 80 mcg/40mcl Subcutaneous Radius International Ltd 2023-02-08 2024-10-01 EU Tymlos Injection, solution 3.12 mg/1.56mL Subcutaneous Radius Health, Inc. 2017-05-01 Not applicable US 
Categories
- ATC Codes
- H05AA04 — Abaloparatide
- Drug Categories
- Amino Acids, Peptides, and Proteins
- Analogs/Derivatives
- Biological Factors
- Bone Density Conservation Agents
- Calcium Homeostasis
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Hypotensive Agents
- Intercellular Signaling Peptides and Proteins
- Parathyroid Hormone-Related Protein
- Parathyroid Hormones and Analogues
- Peptide Hormones
- Peptides
- Proteins
- Systemic Hormonal Preparations, Excl. Sex Hormones and Insulins
- Thyroid Products
- 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
- AVK0I6HY2U
- CAS number
- 247062-33-5
References
- General References
- Shirley M: Abaloparatide: First Global Approval. Drugs. 2017 Aug;77(12):1363-1368. doi: 10.1007/s40265-017-0780-7. [Article]
- Akel M, Parmar M: Abaloparatide. . [Article]
- Hattersley G, Dean T, Corbin BA, Bahar H, Gardella TJ: Binding Selectivity of Abaloparatide for PTH-Type-1-Receptor Conformations and Effects on Downstream Signaling. Endocrinology. 2016 Jan;157(1):141-9. doi: 10.1210/en.2015-1726. Epub 2015 Nov 12. [Article]
- Bhattacharyya S, Pal S, Chattopadhyay N: Abaloparatide, the second generation osteoanabolic drug: Molecular mechanisms underlying its advantages over the first-in-class teriparatide. Biochem Pharmacol. 2019 Aug;166:185-191. doi: 10.1016/j.bcp.2019.05.024. Epub 2019 May 25. [Article]
- Wang MW, Yang Z, Chen X, Zhou SH, Huang GL, Sun JN, Jiang H, Xu WM, Lin HC, Yu X, Sun JP: Activation of PTH1R alleviates epididymitis and orchitis through Gq and beta-arrestin-1 pathways. Proc Natl Acad Sci U S A. 2021 Nov 9;118(45):e2107363118. doi: 10.1073/pnas.2107363118. [Article]
- Bastepe M, Turan S, He Q: Heterotrimeric G proteins in the control of parathyroid hormone actions. J Mol Endocrinol. 2017 May;58(4):R203-R224. doi: 10.1530/JME-16-0221. [Article]
- FDA Approved Drug Products: Tymlos (abaloparatide) for subcutaneous injection [Link]
- EMA Summary of Opinion: Eladynos (abaloparatide) [Link]
- EMA Approved Drug Products: Eladynos (abaloparatide) Subcutaneous Injection [Link]
- Radius Health: European Commission Approves ELADYNOS (Abaloparatide) for the Treatment of Osteoporosis in Postmenopausal Women at Increased Risk of Fracture [Link]
- The Center for Drug Evaluation and Research: Abaloparatide Pharmacology Review [Link]
- External Links
- PubChem Substance
- 347909937
- ChemSpider
- 34443170
- BindingDB
- 50246337
- 1921069
- ChEMBL
- CHEMBL4084894
- Wikipedia
- Abaloparatide
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available Completed Not Available Postmenopausal Osteoporosis 1 somestatus stop reason just information to hide 4 Active Not Recruiting Treatment Arthroplasties, Replacement, Knee / Osteoporosis 1 somestatus stop reason just information to hide 4 Recruiting Treatment Postmenopausal Osteoporosis 1 somestatus stop reason just information to hide 4 Withdrawn Treatment Femoral Fractures 1 somestatus stop reason just information to hide 3 Completed Treatment Osteoporosis / Osteoporosis (Senile) / Osteoporosis Fracture / Osteoporosis Localized to Spine / Osteoporosis of Vertebrae / Osteoporosis Risk / Osteoporosis, Age Related / Postmenopausal Osteoporosis 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection Subcutaneous 80 mcg Injection, solution Subcutaneous 80 μg/dose Injection, solution Subcutaneous 80 mcg/40mcl Injection, solution Subcutaneous 3.12 mg/1.56mL - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US8148333 No 2012-04-03 2027-11-08 US US7803770 No 2010-09-28 2028-03-26 US US8748382 No 2014-06-10 2027-10-03 US US10996208 No 2021-05-04 2038-04-30 US US11255842 No 2020-01-10 2040-01-10 US USRE49444 No 2011-04-28 2031-04-28 US US11680942 No 2020-01-10 2040-01-10 US US11782041 No 2018-04-30 2038-04-30 US US11977067 No 2018-04-30 2038-04-30 US
Properties
- State
- Solid
- Experimental Properties
Property Value Source water solubility Soluble Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General Function
- Receptor for parathyroid hormone and for parathyroid hormone-related peptide. The activity of this receptor is mediated by G proteins which activate adenylyl cyclase and also a phosphatidylinositol-calcium second messenger system
- Specific Function
- G protein-coupled peptide receptor activity
- Gene Name
- PTH1R
- Uniprot ID
- Q03431
- Uniprot Name
- Parathyroid hormone/parathyroid hormone-related peptide receptor
- Molecular Weight
- 66359.98 Da
References
- Jolette J, Attalla B, Varela A, Long GG, Mellal N, Trimm S, Smith SY, Ominsky MS, Hattersley G: Comparing the incidence of bone tumors in rats chronically exposed to the selective PTH type 1 receptor agonist abaloparatide or PTH(1-34). Regul Toxicol Pharmacol. 2017 Apr 4;86:356-365. doi: 10.1016/j.yrtph.2017.04.001. [Article]
- Hattersley G, Dean T, Corbin BA, Bahar H, Gardella TJ: Binding Selectivity of Abaloparatide for PTH-Type-1-Receptor Conformations and Effects on Downstream Signaling. Endocrinology. 2016 Jan;157(1):141-9. doi: 10.1210/en.2015-1726. Epub 2015 Nov 12. [Article]
- FDA Approved Drug Products: Tymlos (abaloparatide) for subcutaneous injection [Link]
- EMA Approved Drug Products: Eladynos (abaloparatide) Subcutaneous Injection [Link]
Drug created at October 21, 2007 22:23 / Updated at February 02, 2023 07:21