Palopegteriparatide
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Identification
- Summary
Palopegteriparatide is a parathyroid hormone analog used to treat hyperparathyroidism in adults.
- Generic Name
- Palopegteriparatide
- DrugBank Accession Number
- DB18676
- Background
Palopegteriparatide is a parathyroid hormone (PTH) analog. Palopegteriparatide is a prodrug consisting of PTH(1-34) conjugated to a methoxy polyethylene glycol carrier (mPEG) via a proprietary TransCon Linker.5 PTH(1-34) contains the N-terminal part of the endogenous PTH molecule.1 Upon administration, PTH is cleaved from palopegteriparatide in a controlled manner to achieve a continuous systemic exposure of active PTH.5 Palopegteriparatide was first approved by the EMA on November 17, 2023, for the treatment of hyperparathyroidism.5 On August 8, 2024, palopegteriparatide was also approved by the FDA.4
- Type
- Biotech
- Groups
- Approved, Investigational
- Biologic Classification
- Protein Based Therapies
Peptides - Protein Chemical Formula
- Not Available
- Protein Average Weight
- 474000.0 Da (approximate)
- Sequences
- Not Available
- Synonyms
- Human parathyroid hormone (PTH) synthetic peptide fragment (1-34), conjugated at the N-terminal amino group via a cleavable linker to O-methylpolyethylene glycol (2 x 20 kDa mPEG); 2-methylalanyl-(1-34)-peptide of parathyroid hormone (Homo sapiens parath
- Mpeg 40000-teriparatide
- Poly(oxy-1,2-ethanediyl), α-hydro-ω-methoxy-, ether with N-[[[2-[[6-[[1-[3-[[3-(2,3-dihydroxypropoxy)propyl]amino]-3-oxopropyl]-2,5-dioxo-3-pyrrolidinyl]thio]hexyl]amino]ethyl]amino]carbonyl]-2-methylalanyl-L-seryl-L-valyl-L-seryl-L-α-glutamyl-L-isole
- Transcon parathyroid hormone (1-34)
- TransCon PTH
- Transcon pth (1-34)
- External IDs
- ACP 014
- ACP-014
- ACP014
Pharmacology
- Indication
Palopegteriparatide is indicated for the treatment of hypoparathyroidism in adults.3,5
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Hypoparathyroidism •••••••••••• ••••• - Contraindications & Blackbox Warnings
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- Pharmacodynamics
Palopegteriparatide is a parathyroid hormone (PTH) analog that causes a sustained release of PTH(1-34), a synthetic PTH that contains the N-terminal part of the endogenous PTH molecule.1 Serum PTH(1-34) and serum calcium concentrations increased in a dose-related manner when palopegteriparatide was administered to healthy volunteers. Exposure-response is not established in subjects with hypoparathyroidism.3
- Mechanism of action
Secreted by the parathyroid glands, endogenous parathyroid hormone (PTH) is an 84-amino acid-long polypeptide that binds to cell-surface parathyroid hormone receptors expressed in various tissues.5 The main receptor is parathyroid hormone 1 receptor (PTH1R), which is highly expressed in osteoblasts, osteocytes, renal tubular cells, and several other tissues.3 PTH maintains extracellular calcium and phosphate homeostasis by increasing serum calcium and decreasing serum phosphate.3 PTH stimulates bone turnover to mobilize calcium and phosphate from bone, promotes renal calcium reabsorption and phosphate excretion, and facilitates active vitamin D synthesis, in turn increasing intestinal absorption of calcium and phosphate.1,3,5 PTH deficiency due to hypoparathyroidism can lead to low bone turnover and structural and dynamic skeletal defects if not addressed.2
Palopegteriparatide is a prodrug that releases PTH(1-34) via autocleavage of the TransCon linker. PTH(1-34) released from palopegteriparatide mimics the biological effects of endogenous PTH.L51124] PTH(1-34) and its active metabolite, PTH(1-33), have similar affinity to and activation of PTH1R as endogenous PTH.5
Target Actions Organism AParathyroid hormone/parathyroid hormone-related peptide receptor ligandHumans - Absorption
PTH Cmax and AUC increased proportionally over a YORVIPATH dosage range of 12 to 24 mcg/day. PTH steady state is achieved after administration of palopegteriparatide for seven days. At steady-state, administration of palopegteriparatide resulted in continuous exposure to released PTH throughout the 24-hour dosing period.3
The median (range) time to reach maximum concentrations (Tmax) of PTH is 4 (4-8) hours.3
- Volume of distribution
The estimated apparent volume of distribution (CV%) of palopegteriparatide is 4.8 (50) L.3 The apparent volume of distribution (CV%) is 8.7 L (18%) for released PTH.5
- Protein binding
Not Available
- Metabolism
Released PTH includes PTH(1-34) and the active metabolite PTH(1-33). PTH(1-33) and PTH(1-34) have comparable affinity to and activation of PTH1R.3 In the liver, most of the PTH is cleaved by cathepsins.5
- Route of elimination
PTH is renally metabolized and cleared.5 In the kidney, most of PTH is excreted by glomerular filtration.5
- Half-life
The apparent half-life of PTH released from palopegteriparatide is approximately 60 hours.3
- Clearance
The estimated clearance (CV%) of palopegteriparatide at steady-state is 0.58 (52) L/day.3
- Adverse Effects
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- Toxicity
There is no information regarding the acute toxicity (LD50) of palopegteriparatide. An accidental overdose of palopegteriparatide may cause hypercalcemia, which can be severe and require medical intervention.3 The manifestations of hypercalcemia may include dehydration, heart palpitations, ECG changes, hypotension, nausea, vomiting, dizziness, muscle weakness, and confusion.5
One subject in Study 1 accidentally received approximately 3-fold the prescribed dose of palopegteriparatide for more than seven consecutive days and developed albumin-corrected serum calcium as high as 16.1 mg/dL, requiring hospitalization.3 After withholding palopegteriparatide, calcium, and active vitamin D, the patient recovered and restarted on the correct dose.5
- 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 softwareAcalabrutinib The therapeutic efficacy of Palopegteriparatide can be decreased when used in combination with Acalabrutinib. Acebutolol The risk or severity of adverse effects can be increased when Acebutolol is combined with Palopegteriparatide. Acetohexamide The therapeutic efficacy of Acetohexamide can be decreased when used in combination with Palopegteriparatide. Afatinib The therapeutic efficacy of Palopegteriparatide can be decreased when used in combination with Afatinib. Aldesleukin The therapeutic efficacy of Palopegteriparatide can be decreased when used in combination with Aldesleukin. - Food Interactions
- No interactions found.
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 Yorvipath Injection, solution 168 μg/0.56ml Subcutaneous Ascendis Pharma Bone Diseases A/s 2024-07-10 Not applicable EU Yorvipath Injection, solution 168 ug/0.56mL Subcutaneous Ascendis Pharma, Endocrinology, Inc. 2024-08-09 Not applicable US Yorvipath Injection, solution 420 μg/1.4ml Subcutaneous Ascendis Pharma Bone Diseases A/s 2024-07-10 Not applicable EU Yorvipath Injection, solution 420 ug/1.4mL Subcutaneous Ascendis Pharma, Endocrinology, Inc. 2024-08-09 Not applicable US Yorvipath Injection, solution 294 μg/0.98ml Subcutaneous Ascendis Pharma Bone Diseases A/s 2024-07-10 Not applicable EU
Categories
- ATC Codes
- H05AA05 — Palopegteriparatide
- 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
- Not Available
Chemical Identifiers
- UNII
- G2N64C3385
- CAS number
- 2222514-07-8
References
- General References
- Rejnmark L: Treatment of Hypoparathyroidism by Re-Establishing the Effects of Parathyroid Hormone. Endocrinol Metab (Seoul). 2024 Apr;39(2):262-266. doi: 10.3803/EnM.2024.1916. Epub 2024 Apr 4. [Article]
- Ish-Shalom S, Caraco Y, Khazen NS, Gershinsky M, Szalat A, Schwartz P, Arbit E, Galitzer H, Tang JC, Burshtein G, Rothner A, Raskin A, Blum M, Fraser WD: Safety and Efficacy of Oral Human Parathyroid Hormone (1-34) in Hypoparathyroidism: An Open-Label Study. J Bone Miner Res. 2021 Jun;36(6):1060-1068. doi: 10.1002/jbmr.4274. Epub 2021 Mar 5. [Article]
- FDA Approved Drug Products: YORVIPATH (palopegteriparatide) injection, for subcutaneous use [Link]
- FDA News Release: FDA approves new drug for hypoparathyroidism, a rare disorder [Link]
- EMA Approved Drug Products: Yorvipath (palopegteriparatide) Subcutaneous Injection [Link]
- External Links
- 2693635
- Wikipedia
- Palopegteriparatide
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 Available Not Available Hypoparathyroidism 1 somestatus stop reason just information to hide 3 Active Not Recruiting Treatment Endocrine System Diseases / Hypoparathyroidism / Parathyroid Diseases 1 somestatus stop reason just information to hide 3 Recruiting Treatment Endocrine System Diseases / Hypoparathyroidism / Parathyroid Diseases / Parathyroid Hormone Deficiency 1 somestatus stop reason just information to hide 2 Active Not Recruiting Treatment Endocrine System Diseases / Hypoparathyroidism / Parathyroid Diseases 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, solution Subcutaneous 168 ug/0.56mL Injection, solution Subcutaneous 168 μg/0.56ml Injection, solution Subcutaneous 168 g/0.56ml Injection, solution Subcutaneous 294 μg/0.98ml Injection, solution Subcutaneous 294 g/0.98ml Injection, solution Subcutaneous 294 ug/0.98mL Injection, solution Subcutaneous 420 g/1.4ml Injection, solution Subcutaneous 420 ug/1.4mL Injection, solution Subcutaneous 420 μg/1.4ml - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Liquid
- Experimental Properties
- Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Ligand
- Curator comments
- Palopegteriparatide is a prodrug that releases PTH(1-34), which binds to its main receptor, parathyroid hormone 1 receptor (PTH1R).
- 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
- FDA Approved Drug Products: YORVIPATH (palopegteriparatide) injection, for subcutaneous use [Link]
Drug created at October 13, 2023 17:15 / Updated at August 23, 2024 02:37