Asfotase alfa
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Identification
- Summary
Asfotase alfa is an enzyme replacement therapy used for the treatment of perinatal/infantile and juvenile onset hypophosphatasia (HPP).
- Brand Names
- Strensiq
- Generic Name
- Asfotase alfa
- DrugBank Accession Number
- DB09105
- Background
Asfotase alfa is a first-in-class bone-targeted enzyme replacement therapy designed to address the underlying cause of hypophosphatasia (HPP)—deficient alkaline phosphatase (ALP). Hypophosphatasia is almost always fatal when severe skeletal disease is obvious at birth. By replacing deficient ALP, treatment with Asfotase Alfa aims to improve the elevated enzyme substrate levels and improve the body's ability to mineralize bone, thereby preventing serious skeletal and systemic patient morbidity and premature death. Asfotase alfa was first approved by Pharmaceuticals and Medicals Devices Agency of Japan (PMDA) on July 3, 2015, then approved by the European Medicine Agency (EMA) on August 28, 2015, and was approved by the U.S. Food and Drug Administration (FDA) on October 23, 2015. Asfotase Alfa is marketed under the brand name Strensiq® by Alexion Pharmaceuticals, Inc. The annual average price of Asfotase Alfa treatment is $285,000.
- Type
- Biotech
- Groups
- Approved, Investigational
- Biologic Classification
- Protein Based Therapies
Fusion proteins - Protein Structure
- Protein Chemical Formula
- C7108H11008N1968O2206S56
- Protein Average Weight
- 180000.0 Da (Approximate)
- Sequences
> Asfotase Alfa Sequence LVPEKEKDPKYWRDQAQETLKYALELQKLNTNVAKNVIMFLGDGMGVSTVTAARILKGQL HHNPGEETRLEMDKFPFVALSKTYNTNAQVPDSAGTATAYLCGVKANEGTVGVSAATERS RCNTTQGNEVTSILRWAKDAGKSVGIVTTTRVNHATPSAAYAHSADRDWYSDNEMPPEAL SQGCKDIAYQLMHNIRDIDVIMGGGRKYMYPKNKTDVEYESDEKARGTRLDGLDLVDTWK SFKPRYKHSHFIWNRTELLTLDPHNVDYLLGLFEPGDMQYELNRNNVTDPSLSEMVVVAI QILRKNPKGFFLLVEGGRIDHGHHEGKAKQALHEAVEMDRAIGQAGSLTSSEDTLTVVTA DHSHVFTFGGYTPRGNSIFGLAPMLSDTDKKPFTAILYGNGPGYKVVGGERENVSMVDYA HNNYQAQSAVPLRHETHGGEDVAVFSKGPMAHLLHGVHEQNYVPHVMAYAACIGANLGHC APASSLKDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIE KTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKDIDDDD DDDDDD
Download FASTA Format- Synonyms
- Asfotase alfa
- External IDs
- ALXN-1215
- ALXN1215
- ENB-0040
- sALP-FcD10
Pharmacology
- Indication
Indicated for the treatment of patients with perinatal/infantile and juvenile onset hypophosphatasia (HPP).
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Infantile-onset hypophosphatasia •••••••••••• Treatment of Juvenile-onset hypophosphatasia •••••••••••• Treatment of Perinatal-onset hypophosphatasia •••••••••••• - Contraindications & Blackbox Warnings
- Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API
- Pharmacodynamics
Perinatal/infantile- and juvenile-onset HPP patients treated with Asfotase alfa had reductions in plasma TNSALP (tissue non-specific alkaline phosphatase) substrates, PPi and pyridoxal 5'-phosphate (PLP) within 6 to 12 weeks of treatment. Reductions in plasma PPi and PLP levels did not correlate with clinical outcomes. Bone biopsy data from perinatal/infantile-onset and juvenile-onset HPP patients treated with Asfotase alfa demonstrated decreases in osteoid volume and thickness indicating improved bone mineralization.
- Mechanism of action
HPP is caused by a deficiency in TNSALP (tissue non-specific alkaline phosphatase) enzyme activity, which leads to elevations in several TNSALP substrates, including inorganic pyrophosphate (PPi). Elevated extracellular levels of PPi block hydroxyapatite crystal growth which inhibits bone mineralization and causes an accumulation of unmineralized bone matrix which manifests as rickets and bone deformation in infants and children and as osteomalacia (softening of bones) once growth plates close, along with muscle weakness. Replacement of the TNSALP enzyme upon Asfotase alfa treatment reduces the enzyme substrate levels.
Target Actions Organism APyrophosphate ligand- Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
Not Available
- Half-life
Approximately 5 days.
- Clearance
Not Available
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
There are no available human data on Asfotase Alfa use in pregnant women to inform a drug associated risk. In animal reproduction studies, Asfotase Alfa administered intravenously to pregnant rats and rabbits during the period of organogenesis showed no evidence of fetotoxicity, embryolethality or teratogenicity at doses causing plasma exposures up to 21 and 24 times, respectively, the exposure at the recommended human dose.
- 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 softwareAbciximab The risk or severity of adverse effects can be increased when Abciximab is combined with Asfotase alfa. Adalimumab The risk or severity of adverse effects can be increased when Adalimumab is combined with Asfotase alfa. Aducanumab The risk or severity of adverse effects can be increased when Asfotase alfa is combined with Aducanumab. Alemtuzumab The risk or severity of adverse effects can be increased when Alemtuzumab is combined with Asfotase alfa. Alirocumab The risk or severity of adverse effects can be increased when Asfotase alfa is combined with Alirocumab. - 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 Strensiq Injection, solution 40 mg/ml Subcutaneous Alexion Europe Sas 2016-09-08 Not applicable EU Strensiq Injection, solution 40 mg/ml Subcutaneous Alexion Europe Sas 2016-09-08 Not applicable EU Strensiq Injection, solution 40 mg/ml Subcutaneous Alexion Europe Sas 2016-09-08 Not applicable EU Strensiq Solution 40 mg / mL Subcutaneous Alexion Pharma Gmbh 2015-10-20 Not applicable Canada Strensiq Solution 40 mg / mL Subcutaneous Alexion Pharma Gmbh Not applicable Not applicable Canada
Categories
- ATC Codes
- A16AB13 — Asfotase alfa
- Drug Categories
- Alimentary Tract and Metabolism
- Amino Acids, Peptides, and Proteins
- Antibodies
- Blood Proteins
- Enzyme Replacement Therapy
- Enzymes
- Enzymes and Coenzymes
- Esterases
- Globulins
- Hydrolases
- Immunoglobulin Isotypes
- Immunoglobulins
- Immunoproteins
- Phosphoric Monoester Hydrolases
- Proteins
- Recombinant Proteins
- Serum Globulins
- Tissue-nonspecific Alkaline Phosphatase
- 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
- Z633861EIM
- CAS number
- 1174277-80-5
References
- General References
- Whyte MP: Hypophosphatasia - aetiology, nosology, pathogenesis, diagnosis and treatment. Nat Rev Endocrinol. 2016 Apr;12(4):233-46. doi: 10.1038/nrendo.2016.14. Epub 2016 Feb 19. [Article]
- Whyte MP, Rockman-Greenberg C, Ozono K, Riese R, Moseley S, Melian A, Thompson DD, Bishop N, Hofmann C: Asfotase Alfa Treatment Improves Survival for Perinatal and Infantile Hypophosphatasia. J Clin Endocrinol Metab. 2016 Jan;101(1):334-42. doi: 10.1210/jc.2015-3462. Epub 2015 Nov 3. [Article]
- Whyte MP, Greenberg CR, Salman NJ, Bober MB, McAlister WH, Wenkert D, Van Sickle BJ, Simmons JH, Edgar TS, Bauer ML, Hamdan MA, Bishop N, Lutz RE, McGinn M, Craig S, Moore JN, Taylor JW, Cleveland RH, Cranley WR, Lim R, Thacher TD, Mayhew JE, Downs M, Millan JL, Skrinar AM, Crine P, Landy H: Enzyme-replacement therapy in life-threatening hypophosphatasia. N Engl J Med. 2012 Mar 8;366(10):904-13. doi: 10.1056/NEJMoa1106173. [Article]
- FDA Approved Drug Products: Strensiq (Asfotase Alfa) Subcutaneous Injection [Link]
- External Links
- KEGG Drug
- D10595
- PubChem Substance
- 347910406
- 1720259
- ChEMBL
- CHEMBL2108311
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Asfotase_alfa
- FDA label
- Download (1.25 MB)
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 Approved for Marketing Not Available Hypophosphatasia (HPP) 1 somestatus stop reason just information to hide Not Available Completed Not Available Hypophosphatasia (HPP) 1 somestatus stop reason just information to hide Not Available Recruiting Not Available Hypophosphatasia (HPP) 1 somestatus stop reason just information to hide 4 Completed Treatment Hypophosphatasia (HPP) 1 somestatus stop reason just information to hide 4 Withdrawn Treatment Hypophosphatasia (HPP) 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, solution Subcutaneous 100 MG/ML Injection, solution Subcutaneous 40 MG/ML Solution Subcutaneous 100 mg / mL Solution Subcutaneous 18 mg/0.45mL Solution Subcutaneous 28 mg/0.7mL Solution Subcutaneous 40 mg/1mL Solution Subcutaneous 40 mg / mL Solution Subcutaneous 80 mg/0.8mL Injection, solution Subcutaneous 18 mg/0.45ml Injection, solution Subcutaneous 28 mg/0.7ml Injection, solution Subcutaneous 40 mg/1.0ml Injection, solution Subcutaneous 80 mg/0.8ml - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US7763712 No 2010-07-27 2026-07-15 US
Properties
- State
- Liquid
- Experimental Properties
- Not Available
Targets
References
- Whyte MP, Greenberg CR, Salman NJ, Bober MB, McAlister WH, Wenkert D, Van Sickle BJ, Simmons JH, Edgar TS, Bauer ML, Hamdan MA, Bishop N, Lutz RE, McGinn M, Craig S, Moore JN, Taylor JW, Cleveland RH, Cranley WR, Lim R, Thacher TD, Mayhew JE, Downs M, Millan JL, Skrinar AM, Crine P, Landy H: Enzyme-replacement therapy in life-threatening hypophosphatasia. N Engl J Med. 2012 Mar 8;366(10):904-13. doi: 10.1056/NEJMoa1106173. [Article]
- FDA Approved Drug Products: Strensiq (Asfotase Alfa) Subcutaneous Injection [Link]
Drug created at September 16, 2015 22:39 / Updated at June 03, 2022 07:24