|
| Primary information |
|---|
| ID | 10729 |
| Therapeutic ID | Th1166 |
| Protein Name | Asfotase Alfa |
| Sequence | >Th1166_Asfotase_Alfa
LVPEKEKDPKYWRDQAQETLKYALELQKLNTNVAKNVIMFLGDGMGVSTVTAARILKGQLHHNPGEETRLEMDKFPFVALSKTYNTNAQVPDSAGTATAYLCGVKANEGTVGVSAATERSRCNTTQGNEVTSILRWAKDAGKSVGIVTTTRVNHATPSAAYAHSADRDWYSDNEMPPEALSQGCKDIAYQLMHNIRDIDVIMGGGRKYMYPKNKTDVEYESDEKARGTRLDGLDLVDTWKSFKPRYKHSHFIWNRTELLTLDPHNVDYLLGLFEPGDMQYELNRNNVTDPSLSEMVVVAIQILRKNPKGFFLLVEGGRIDHGHHEGKAKQALHEAVEMDRAIGQAGSLTSSEDTLTVVTADHSHVFTFGGYTPRGNSIFGLAPMLSDTDKKPFTAILYGNGPGYKVVGGERENVSMVDYAHNNYQAQSAVPLRHETHGGEDVAVFSKGPMAHLLHGVHEQNYVPHVMAYAACIGANLGHCAPASSLKDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGKDIDDDDDDDDDD
|
| Molecular Weight | 180008 |
| Chemical Formula | C7108H11008N1968O2206S64 |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | Approximately 5 days. |
| Description | Asfotase Alfa is a first-in-class bone-targeted enzyme replacement therapy designed to address the underlying cause of hypophosphatasia (HPP)â€â€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. |
| Indication/Disease | Indicated for the treatment of patients with perinatal/infantile and juvenile onset hypophosphatasia (HPP). |
| 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. |
| 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. |
| Metabolism | NA |
| Absorption | NA |
| NA |
| Clearance | NA |
| Categories | Enzymes Alimentary Tract and Metabolism |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Pyrophosphate |
| Brand Name | Strensiq |
| Company | Alexion Pharmaceuticals Inc. |
| Brand Description | Alexion Pharmaceuticals Inc. |
| Prescribed For | STRENSIQâ„¢ is indicated for the treatment of patients with perinatal/infantile-and juvenile-onset hypophosphatasia (HPP). |
| Chemical Name | NA |
| Formulation | 40 mg/mL |
| Physical Appearance | Solution |
| Route of Administration | Subcutaneous |
| Recommended Dosage | The recommended dosage regimen of STRENSIQ for the treatment of perinatal/infantileonset HPP is 6 mg/kg per week administered subcutaneously as either: 2 mg/kg three times per week, or 1 mg/kg six times per week. Injection site reactions may limit the tolerability of the six times per week regimen |
| Contraindication | NA |
| Side Effects | Hypersensitivity Reactions; Lipodystrophy; Ectopic Calcifications. |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |