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| Primary information |
|---|
| ID | 15266 |
| Therapeutic ID | Th1579 |
| Protein Name | Albutrepenonacog alfa |
| Sequence | >Th1579_Albutrepenonacog_alfa
YNSGKLEEFVQGNLERECMEEKCSFEEAREVFENTERTTEFWKQYVDGDQCESNPCLNGGSCKDDINSYECWCPFGFEGKNCELDVTCNIKNGRCEQFCKNSADNKVVCSCTEGYRLAENQKSCEPAVPFPCGRVSVSQTSKLTRAETVFPDVDYVNSTEAETILDNITQSTQSFNDFTRVVGGEDAKPGQFPWQVVLNGKVDAFCGGSIVNEKWIVTAAHCVETGVKITVVAGEHNIEETEHTEQKRNVIRIIPHHNYNAAINKYNHDIALLELDEPLVLNSYVTPICIADKEYTNIFLKFGSGYVSGWGRVFHKGRSALVLQYLRVPLVDRATCLRSTKFTIYNNMFCAGFHEGGRDSCQGDSGGPHVTEVEGTSFLTGIISWGEECAMKGKYGIYTKVSRYVNWIKEKTKLTPVSQTSKLTRAETVFPDVDAHKSEVAHRFKDLGEENFKALVLIAFAQYLQQCPFEDHVKLVNEVTEFAKTCVADESAENCDKSLHTLFGDKLCTVATLRETYGEMADCCAKQEPERNECFLQHKDDNPNLPRLVRPEVDVMCTAFHDNEETFLKKYLYEIARRHPYFYAPELLFFAKRYKAAFTECCQAADKAACLLPKLDELRDEGKASSAKQRLKCASLQKFGERAFKAWAVARLSQRFPKAEFAEVSKLVTDLTKVHTECCHGDLLECADDRADLAKYICENQDSISSKLKECCEKPLLEKSHCIAEVENDEMPADLPSLAADFVESKDVCKNYAEAKDVFLGMFLYEYARRHPDYSVVLLLRLAKTYETTLEKCCAAADPHECYAKVFDEFKPLVEEPQNLIKQNCELFEQLGEYKFQNALLVRYTKKVPQVSTPTLVEVSRNLGKVGSKCCKHPEAKRMPCAEDYLSVVLNQLCVLHEKTPVSDRVTKCCTESLVNRRPCFSALEVDETYVPKEFNAETFTFHADICTLSEKERQIKKQTALVELVKHKPKATKEQLKAVMDDFAAFVEKCCKADDKETCFAEEGKKLVAASQAALGL
|
| Molecular Weight | 125000 |
| Chemical Formula | C5077N7846O1588PS67 |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | The fusion of the rFIX with rAlbumin prolongs the elimination half-life of rIX-RFP in the circulation. The reported half-life in clinical trials is 92 hours.[A32547] |
| Description | Albutrepenonacog alfa (rIX-RFP) is a recombinant fusion protein that links a recombinant coagulation factor IX (rFIX) with a recombinant human albumin (rAlbumin).[A32547] It was developed by CSL Behring Canada, Inc and approved by Health Canada on April 26, 2017. It was also approved by FDA and EMA in 2016. It is currently marketed in the forms of 250, 500, 1000 and 2000 IU/vial.[L2305] |
| Indication/Disease | Under the EMA and FDA, rIX-RFP is indicated in the treatment of hemophilia B.[L2306] For Health Canada, rIX-FRP is also indicated to prevent or reduce bleeding episodes.[L2305] Hemophilia B is the second most common type of hemophilia. It is a rare inherited bleeding disorder caused by reduced or absent levels of factor IX (FIX). The FIX is a vitamin K-dependent plasma protease that when activated is involved in the blood coagulation cascade.[A32551] The hemophilia B is caused by mutations in the _FIX_ gene which can cause different phenotypes. The severe form is characterized by the presence of spontaneous and recurring bleeds into the joints and muscles and excessive bleeding after trauma or surgery.[A32552] |
| Pharmacodynamics | Clinical trials with rIX-RFP in patients with moderately to severe hemophilia B demonstrated a lower annualized spontaneous, total and joint bleeding rates. It was also efficient against bleeding episodes and maintenance of hemostasis in the perioperative setting when compared with on-demand treatment. The administration of rIX-RFP presented no reports of inhibitor development.[A32547] |
| Mechanism of Action | The current therapies against hemophilia B are hampered by the short half-life of the replacement FIX therapy.[A32547] Thus, to solve this problem, in rIX-RFP there is the fusion of rFIX with rAlbumin which presents a much longer half-life and it does not present interactions with the immune system.[A32547] The administration of rIX-RFP increases the plasma concentration of FIX, thus addressing the coagulation deficiency of the patient. rIX-RFP is able to circulate in the plasma as an intact zymogen thanks to the pH-dependent binding to FcRn which is a normal protection pathway from lysosomal degradation of albumin. When the FIX is needed, rAlbumin is cleaved by the same proteases that activate the FIX.[A32547] |
| Toxicity | rIX-RFP is very well tolerated.[A32547]Mutaginicity trials were performed and they confirmed an absent mutagenic potential.[L2305]Fertility studies have not been performed. Developmental studies are not of major importance as there is a very low rate of incidence of hemophilia B in females. |
| Metabolism | The metabolism of rIX-RFP is not relevant as it is a recombinant protein and it is thought to be metabolized to peptides and amino acids.[L2313] |
| Absorption | rIX-RFP absorption is very rapid as it is directly administered intravenously. In clinical trials, the maximum plasma concentration, area under the curve and mean residence time are reported to be approximately 55 IU/dL, 5500 IU.h/dL and 125 hours respectively.[A32547] |
| The reported volume of distribution for rIX-RFP according to phase I/II and III clinical trials is 95 ml/kg.[A32556] |
| Clearance | In clinical trials, the weight-adjusted clearance in children and adults is reported to be 1.1 and 0.9 ml/h/kg.[A32547] |
| Categories | Enzymes and Coenzymes |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Coagulation factor X |
| Brand Name | Idelvion |
| Company | CSL Behring Lengnau AG |
| Brand Description | CSL Behring Lengnau AG |
| Prescribed For | Intravenous |
| Chemical Name | 2000 [iU]/5mL |
| Formulation | IDELVION, Coagulation Factor IX (Recombinant), Albumin Fusion Protein (rIX-FP), is contraindicated in patients who have a known hypersensitivity to IDELVION, any of its components, excipients or hamster protein. For a complete listing, see Dosage Forms, Composition And Packaging. |
| Physical Appearance | headache, dizziness, rash, and infusion site reaction |
| Route of Administration | Idelvion is used to treat or prevent bleeding in people with hemophilia B. This medication is not for treating people with hemophilia A factor VIII deficiency. Idelvion may also be used for purposes not listed in this medication guide. Warnings Follow all directions on your medicine label and package.... |
| Recommended Dosage | Idelvion is a prescription medicine used as prophylaxis and to treat the symptoms of Hemophilia B. Idelvion may be used alone or with other medications. |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |