Asfotase alfa

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Asfotase alfa
Clinical data
Trade namesStrensiq
AHFS/Drugs.comstrensiq
License data
Pregnancy
category
  • Insufficient data
Routes of
administration
Subcutaneous injection
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability46–98%
Elimination half-life2.3±0.6 days
Identifiers
CAS Number
DrugBank
ChemSpider
  • none
UNII
KEGG
Chemical and physical data
FormulaC7108H11008N1968O2206S56 (protein part)
Molar mass~160 kDa (protein part)
~180 kDa (including sugars)

Asfotase alfa (trade name Strensiq) is a drug used in the treatment of patients with perinatal/infantile- and juvenile-onset hypophosphatasia.[1]

Asfotase alfa is manufactured by Alexion Pharmaceuticals and It was granted breakthrough therapy designation by the US Food and Drug Administration in 2015.[2] It was approved in October 2015 in the US[1] and in August 2015 in Europe.[3]

Adverse effects[edit]

The most common adverse effects in studies included injection site reactions (pain, itching, erythema, etc.), headache, limb pain, and haematoma. Possible rare side effects could not be assessed because of the low number of patients.[4][5]

Interactions[edit]

Asfotase alfa interferes with alkaline phosphatase measurements. As asfotase alfa is a glycoprotein (as opposed to a small molecule), no relevant interactions via the cytochrome P450 liver enzymes are expected.[4]

Pharmacology[edit]

Mechanism of action[edit]

Hypophosphatasia is caused by a genetic defect of tissue-nonspecific alkaline phosphatase (TNSALP), an enzyme that plays a role in bone mineralization. Asfotase alfa is a recombinant glycoprotein that contains the catalytic domain (the active site) of TNSALP. It is thus a form of enzyme replacement therapy.[4][5]

Pharmacokinetics[edit]

After subcutaneous injection, asfotase alfa has a bioavailability of 46–98% and reaches highest blood plasma concentrations after 24 to 48 hours. Elimination half life is 2.3±0.6 days on average.[4]

Chemistry[edit]

The peptide part of the glycoprotein asfotase alfa consists of two identical chains of 726 amino acids each, containing (1) the catalytic domain of TNSALP, (2) the Fc region of human immunoglobulin G1, and (3) a sequence of ten L-aspartate residues. The two chains are linked by two disulfide bridges. Each chain also contains four internal disulfide bridges.[4][5]

The complete peptide sequence of one chain is[6]

LVPEKEKDPKYWRDQAQETLKYALELQKLNTNVAKNVIMFLGDGMGVSTVTAARILKGQL
HHNPGEETRLEMDKFPFVALSKTYNTNAQVPDSAGTATAYLCGVKANEGTVGVSAATERS
RCNTTQGNEVTSILRWAKDAGKSVGIVTTTRVNHATPSAAYAHSADRDWYSDNEMPPEAL
SQGCKDIAYQLMHNIRDIDVIMGGGRKYMYPKNKTDVEYESDEKARGTRLDGLDLVDTWK
SFKPRYKHSHFIWNRTELLTLDPHNVDYLLGLFEPGDMQYELNRNNVTDPSLSEMVVVAI
QILRKNPKGFFLLVEGGRIDHGHHEGKAKQALHEAVEMDRAIGQAGSLTSSEDTLTVVTA
DHSHVFTFGGYTPRGNSIFGLAPMLSDTDKKPFTAILYGNGPGYKVVGGERENVSMVDYA
HNNYQAQSAVPLRHETHGGEDVAVFSKGPMAHLLHGVHEQNYVPHVMAYAACIGANLGHC
APASSLKDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEV
KFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIE
KTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKT
TPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKDIDDDD
DDDDDD

(the ten "D"s representing the aspartate residues).

Asfotase alfa is produced in Chinese hamster ovary cells.[4]

References[edit]

  1. ^ a b FDA approves new treatment for rare metabolic disorder.
  2. ^ CDER Breakthrough Therapy Designation Approvals.
  3. ^ European Medicines Agency: Strensiq authorisation details.
  4. ^ a b c d e f Haberfeld, H, ed. (2015). Austria-Codex (in German). Vienna: Österreichischer Apothekerverlag. Strensiq Injektionslösung.
  5. ^ a b c FDA Professional Drug Information for Strensiq.
  6. ^ DrugBank: Asfotase Alfa.

External links[edit]