Pharmacology
Mechanism of action
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. Pharmacokinetics
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 five days. Chemistry
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 at the carboxy terminus. The two chains are linked by two disulfide bridges. Each chain also contains four internal disulfide bridges.The complete peptide sequence of one chain is
LVPEKEKDPK YWRDQAQETL KYALELQKLN TNVAKNVIMF LGDGMGVSTV TAARILKGQL
HHNPGEETRL EMDKFPFVAL SKTYNTNAQV PDSAGTATAY LCGVKANEGT VGVSAATERS
RCNTTQGNEV TSILRWAKDA GKSVGIVTTT RVNHATPSAA YAHSADRDWY SDNEMPPEAL
SQGCKDIAYQ LMHNIRDIDV IMGGGRKYMY PKNKTDVEYE SDEKARGTRL DGLDLVDTWK
SFKPRYKHSH FIWNRTELLT LDPHNVDYLL GLFEPGDMQY ELNRNNVTDP SLSEMVVVAI
QILRKNPKGF FLLVEGGRID HGHHEGKAKQ ALHEAVEMDR AIGQAGSLTS SEDTLTVVTA
DHSHVFTFGG YTPRGNSIFG LAPMLSDTDK KPFTAILYGN GPGYKVVGGE RENVSMVDYA
HNNYQAQSAV PLRHETHGGE DVAVFSKGPM AHLLHGVHEQ NYVPHVMAYA ACIGANLGHC
APASSLKDKT HTCPPCPAPE LLGGPSVFLF PPKPKDTLMI SRTPEVTCVV VDVSHEDPEV
KFNWYVDGVE VHNAKTKPRE EQYNSTYRVV SVLTVLHQDW LNGKEYKCKV SNKALPAPIE
KTISKAKGQP REPQVYTLPP SREEMTKNQV SLTCLVKGFY PSDIAVEWES NGQPENNYKT
TPPVLDSDGS FFLYSKLTVD KSRWQQGNVF SCSVMHEALH NHYTQKSLSL SPGKDIDDDD
DDDDDD 

Asfotase alfa is produced in Chinese hamster ovary cells.
Asfotase alfa, sold under the brand name Strensiq, is a medication used in the treatment of people with perinatal/infantile- and juvenile-onset hypophosphatasia.The most common side effects include injection site reactions, hypersensitivity reactions (such as difficulty breathing, nausea, dizziness and fever), lipodystrophy (a loss of fat tissue resulting in an indentation in the skin or a thickening of fat tissue resulting in a lump under the skin) at the injection site, and ectopic calcifications of the eyes and kidney.The enzyme tissue non-specific alkaline phosphatase (ALP) plays a key role in creating and maintaining healthy bones, and managing calcium and phosphate in the body. People with hypophosphatasia cannot make enough working ALP, which leads to weak bones. Asfotase alfa is a version of the human ALP enzyme and serves as a replacement, thereby increasing levels of working ALP. Medical uses
In the United States, asfotase alfa is indicated for the treatment of people with perinatal/infantile- and juvenile-onset hypophosphatasia (HPP).In the European Union, asfotase alfa is indicated for long-term enzyme replacement therapy in people with paediatric-onset hypophosphatasia to treat the bone manifestations of the disease. Adverse effects
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. Interactions
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.