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| Primary information |
|---|
| ID | 16383 |
| Therapeutic ID | Th1893 |
| Protein Name | Sutimlimab |
| Sequence | >Th1893_Sutimlimab
EVQLVESGGGLVKPGGSLRLSCAASGFTFSNYAMSWVRQAPGKGLEWVATISSGGSHTYYLDSVKGRFTISRDNSKNTLYLQMNSLRAEDTALYYCARLFTGYAMDYWGQGTLVTVSSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK
|
| Molecular Weight | 147000.0 Da |
| Chemical Formula | C6436H9934O2012N1700S46 |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | ,At the approved recommended dosage, the terminal elimination half-life of sutimlimab is 21 days. |
| Description | Cold agglutinin disease (CAD) is a type of autoimmune hemolytic anemia (AIHA) in which autoantibodies directed against red blood cell surface antigens cause hemolysis at low (3-4°C) temperatures.2,5 This cold subtype accounts for approximately 15-25% of all AIHA and is more common in the elderly.3,5 In approximately 90% of cases, patients develop immunoglobulin M (IgM) autoantibodies towards the I antigen on erythrocytes - these antibodies react optimally at 4°C and are therefore referred to as "cold agglutinin".1 Hemolysis in patients with CAD is driven by complement activation, which initiates a cascade that ultimately leads to both intra- and extravascular hemolysis.3 The most common presenting symptoms in patients with CAD are chronic anemia, acrocyanosis, and Raynaud phenomenon. |
| Indication/Disease | Sutimlimab is indicated to decrease the need for red blood cell transfusion due to hemolysis in adult patients with cold agglutinin disease. |
| Pharmacodynamics | Following a single sutimlimab injection, >90% inhibition of the complement pathway was observed, and this inhibition was sustained when concentrations of sutimlimab were ≥100 mcg/mL. As sutimlimab can impair the complement-mediated immune response, patients requiring therapy should receive all appropriate vaccinations against encapsulated bacteria at least 2 weeks prior to its initiation.4 Patients undergoing treatment with sutimlimab are at a higher risk of serious infections, especially those caused by encapsulated bacteria such as Neisseria meningitides or Streptococcus pneumoniae, and should be monitored closely throughout therapy for evidence of developing or ongoing infections. |
| Mechanism of Action | Hemolysis associated with cold agglutinin disease is driven by the activation of the complement system. Cold agglutinins transiently bind erythrocytes as they circulate through cooler parts of the body (e.g. the extremities) - as they circulate back to warmer areas, C1q esterase activates C4 and C2, which generates C3 convertase, an enzyme which cleaves C3 into C3a and C3b.3 At this stage, the erythrocytes tagged with C3b can be sequestered by macrophages in the reticuloendothelial system, ultimately leading to extravascular hemolysis.Alternatively, C3b may be further cleaved into C3c and C3d - if complement activation continues past the C3 step, the membrane attack complex with C5b-C9 may form, which causes intravascular hemolysis. |
| Toxicity | Not Available |
| Metabolism | As with other therapeutic proteins, sutimlimab likely undergoes catabolism to smaller peptides and amino acids. |
| Absorption | When administered at the approved weight-based recommended dosage, the exposure to sutimlimab increases proportionately with increasing dosage.4 Steady-state concentrations are achieved by week 7 of therapy. |
| At steady-state, the volume of distribution of sutimlimab in patients with cold agglutinin disease was approximately 5.8 L. |
| Clearance | At the approved recommended dosage, the clearance of sutimlimab is 0.14 L/day.4 The clearance of sutimlimab varies at different doses due to target-mediated drug disposition at lower concentrations |
| Categories | Amino Acids, Peptides, and Proteins,Antibodies,Antibodies, Monoclonal,Blood Proteins,Classical Complement Pathway Inhibitor,Globulins,Immunoglobulins,Immunoproteins,Proteins,Serum Globulins |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Complement C1s subcomponent |
| Brand Name | Enjaymo |
| Company | Bioverativ U.S. LLC. |
| Brand Description | Bioverativ U.S. LLC. |
| Prescribed For | Intravenous |
| Chemical Name | 50 mg/1mL |
| Formulation | ENJAYMO is contraindicated in patients with known hypersensitivity to sutimlimab-jome or any of the inactive ingredients |
| Physical Appearance | hives, difficulty breathing, swelling of your face, lips, tongue, or throat, muscle aches, flu-like symptoms, severe swelling, pain and redness around the injection site or a wound, joint pain or swelling, fever, shortness of breath, rapid heartbeat, and rash |
| Route of Administration | Sutimlimab-jome, a classical complement inhibitor, is a humanized monoclonal antibody expressed by recombinant in Chinese hamster ovary (CHO) cells and produced in vitro using standard mammalian cell culture methods. Sutimlimab-jome is composed of two heterodimers. Each heterodimer is composed of a heavy and a light polypeptide chain. Each heavy chain (H-chain) is composed of 445 amino acids and each light chain (L-chain) contains 216 amino acids. Sutimlimab-jome has a molecular weight of approximately 147 kDa. |
| Recommended Dosage | Enjaymo is a prescription medicine used to treat the symptoms of Cold Agglutinin Disease. |
| Contraindication | NA |
| Side Effects | ENJAYMO (sutimlimab-jome) injection is a sterile, clear to slightly opalescent, colorless to slightly yellow, preservative-free solution for intravenous use. Each single-dose vial contains 1,100 mg sutimlimab-jome at a concentration of 50 mg/mL with a pH of 6.1. Each mL contains 50 mg of sutimlimab-jome and also contains polysorbate 80 (0.2 mg), sodium chloride (8.18 mg), sodium phosphate dibasic heptahydrate (0.48 mg), sodium phosphate monobasic monohydrate (1.13 mg), and Water for Injection, USP. |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |