Asfotase alfa

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
Db09105
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).

Pharmacology
Accelerate your drug discovery research with the industry’s only fully connected ADMET dataset, ideal for:
Machine Learning
Data Science
Drug Discovery
Accelerate your drug discovery research with our fully connected ADMET dataset
Learn more
Associated Conditions
Contraindications & Blackbox Warnings
Contraindications
Contraindications & Blackbox Warnings
With our commercial data, access important information on dangerous risks, contraindications, and adverse effects.
Learn more
Our Blackbox Warnings cover Risks, Contraindications, and Adverse Effects
Learn more
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.

TargetActionsOrganism
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
Medicalerrors
Reduce medical errors
and improve treatment outcomes with our comprehensive & structured data on drug adverse effects.
Learn more
Reduce medical errors & improve treatment outcomes with our adverse effects data
Learn more
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.
DrugInteraction
AbciximabThe risk or severity of adverse effects can be increased when Abciximab is combined with Asfotase alfa.
AdalimumabThe risk or severity of adverse effects can be increased when Adalimumab is combined with Asfotase alfa.
AlemtuzumabThe risk or severity of adverse effects can be increased when Alemtuzumab is combined with Asfotase alfa.
AlirocumabThe risk or severity of adverse effects can be increased when Asfotase alfa is combined with Alirocumab.
AnsuvimabThe risk or severity of adverse effects can be increased when Asfotase alfa is combined with Ansuvimab.
Anthrax immune globulin humanThe risk or severity of adverse effects can be increased when Anthrax immune globulin human is combined with Asfotase alfa.
Antilymphocyte immunoglobulin (horse)The risk or severity of adverse effects can be increased when Asfotase alfa is combined with Antilymphocyte immunoglobulin (horse).
Antithymocyte immunoglobulin (rabbit)The risk or severity of adverse effects can be increased when Antithymocyte immunoglobulin (rabbit) is combined with Asfotase alfa.
AtezolizumabThe risk or severity of adverse effects can be increased when Asfotase alfa is combined with Atezolizumab.
AtoltivimabThe risk or severity of adverse effects can be increased when Asfotase alfa is combined with Atoltivimab.
Interactions
Improve patient outcomes
Build effective decision support tools with the industry’s most comprehensive drug-drug interaction checker.
Learn more
Food Interactions
No interactions found.

Products

Products
Comprehensive & structured drug product info
From application numbers to product codes, connect different identifiers through our commercial datasets.
Learn more
Easily connect various identifiers back to our datasets
Learn more
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
StrensiqSolution18 mg/0.45mLSubcutaneousAlexion Pharmaceuticals, Inc.2015-10-23Not applicableUS flag
StrensiqInjection, solution40 mg/mlSubcutaneousAlexion Europe Sas2016-09-08Not applicableEU flag
StrensiqSolution40 mg / mLSubcutaneousAlexion Pharma Gmbh2016-06-07Not applicableCanada flag
StrensiqInjection, solution100 mg/mlSubcutaneousAlexion Europe Sas2016-09-08Not applicableEU flag
StrensiqInjection, solution40 mg/mlSubcutaneousAlexion Europe Sas2016-09-08Not applicableEU flag
StrensiqSolution40 mg/1mLSubcutaneousAlexion Pharmaceuticals, Inc.2015-10-23Not applicableUS flag
StrensiqSolution40 mg / mLSubcutaneousAlexion Pharma GmbhNot applicableNot applicableCanada flag
StrensiqSolution40 mg / mLSubcutaneousAlexion Pharma Gmbh2016-06-01Not applicableCanada flag
StrensiqInjection, solution40 mg/mlSubcutaneousAlexion Europe Sas2016-09-08Not applicableEU flag
StrensiqInjection, solution40 mg/mlSubcutaneousAlexion Europe Sas2016-09-08Not applicableEU flag

Categories

ATC Codes
A16AB13 — Asfotase alfa
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
Z633861EIM
CAS number
1174277-80-5

References

General References
  1. 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]
  2. 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]
  3. 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]
  4. FDA Approved Drug Products: Strensiq (Asfotase Alfa) Subcutaneous Injection [Link]
KEGG Drug
D10595
PubChem Substance
347910406
RxNav
1720259
ChEMBL
CHEMBL2108311
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Asfotase_alfa
AHFS Codes
  • 44:00.00 — Enzymes
FDA label
Download (1.25 MB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedTreatmentHypophosphatasia1
4WithdrawnTreatmentHypophosphatasia1
2CompletedTreatmentHypophosphatasia4
2CompletedTreatmentHypophosphatasia (HPP)2
2WithdrawnTreatmentHypophosphatasia1
2, 3CompletedTreatmentHypophosphatasia1
1CompletedTreatmentHypophosphatasia (HPP)1
1, 2CompletedTreatmentHypophosphatasia (HPP)1
Not AvailableApproved for MarketingNot AvailableHypophosphatasia1
Not AvailableEnrolling by InvitationNot AvailableHypophosphatasia1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
Injection, solutionSubcutaneous
Injection, solutionSubcutaneous100 mg/ml
Injection, solutionSubcutaneous40 mg/ml
SolutionSubcutaneous100 mg / mL
SolutionSubcutaneous18 mg/0.45mL
SolutionSubcutaneous28 mg/0.7mL
SolutionSubcutaneous40 mg/1mL
SolutionSubcutaneous40 mg / mL
SolutionSubcutaneous80 mg/0.8mL
Injection, solutionSubcutaneous18 mg/0.45ml
Injection, solutionSubcutaneous28 mg/0.7ml
Injection, solutionSubcutaneous40 mg/1.0ml
Injection, solutionSubcutaneous80 mg/0.8ml
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US7763712No2010-07-272026-07-15US flag

Properties

State
Liquid
Experimental Properties
Not Available

Targets

Drugtargets
Accelerate your drug discovery research
with our fully connected ADMET & drug target dataset.
Learn more
Accelerate your drug discovery research with our ADMET & drug target dataset
Learn more
Kind
Small molecule
Organism
Not Available
Pharmacological action
Yes
Actions
Ligand
References
  1. 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]
  2. FDA Approved Drug Products: Strensiq (Asfotase Alfa) Subcutaneous Injection [Link]

Drug created on September 16, 2015 22:39 / Updated on May 15, 2021 12:14