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| Primary information |
|---|
| ID | 15916 |
| Therapeutic ID | Th1643 |
| Protein Name | Satralizumab |
| Sequence | >Th1643_Satralizumab
QVQLQESGPGLVKPSETLSLTCAVSGHSISHDHAWSWVRQPPGEGLEWIGFISYSGITNYNPSLQGRVTISRDNSKNTLYLQMNSLRAEDTAVYYCARSLARTTAMDYWGEGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVERKSCVECPPCPAPPVAGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKGLPAPIEKTISKTKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPMLDSDGSFFLYSKLTVDKSRWQEGNVFSCSVMHEALHAHYTQKSLSLSP
|
| Molecular Weight | 143000 |
| Chemical Formula | NA |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | The terminal half-life of satralizumab is approximately 30 days (range 22-37 days).[L15536] |
| Description | Satralizumab is a recombinant humanized monoclonal antibody targeted against human interleukin-6 (IL-6) receptors, similar to [tocilizumab], which is produced in Chinese hamster ovary cells and based on an IgG2 framework.[L15536] Satralizumab is used in the treatment of neuromyelitis optica spectrum disorder (NMOSD), a rare autoimmune inflammatory disorder of the central nervous system (CNS) involving demyelinating lesions in the optic nerve, spinal cord, brainstem, and cerebrum.[A218551] Some of the pro-inflammatory mechanisms involved in NMOSD are thought to be mediated, at least in part, by IL-6, including increased production of anti-aquaporin-4 (AQP4) autoantibodies and increased permeability of the blood-brain barrier, which allows for the passage of pro-inflammatory mediators into the CNS.[A218546,A218551] Satralizumab is thought to exert its therapeutic benefits by blocking IL-6 receptors and, subsequently, these inflammatory responses. Enspryng®, a satralizumab formulation developed by Chugai Pharmaceutical and Roche,[L15536] is uniquely formulated with "recycling antibody technology" whereby the association of satralizumab to IL-6 receptors occurs in a pH-dependent manner[A218551] - this allows satralizumab to bind an IL-6 receptor until it reaches an endosome, after which the drug may dissociate from the receptor and move back into the plasma to act again. This novel mechanism effectively increases the duration of action of satralizumab, as it allows for single drug molecules to interact with multiple endogenous IL-6 receptors prior to elimination. Satralizumab was first approved for use in Canada in June 2020 for the treatment of AQP4 antibody-positive patients with NMOSD.[A218551] It received subsequent approvals in Switzerland and Japan,[A218551] and was approved for use by the FDA in August 2020,[L15566] becoming the 3rd treatment to receive FDA approval for NMOSD (after [eculizumab] in June 2019 and [inebilizumab] in June 2020). |
| Indication/Disease | Satralizumab is indicated for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adult patients who are anti-aquaporin-4 (AQP4) antibody positive.[L15536] In Canada, it is also used in adolescent patients for the same indication.[L15546] |
| Pharmacodynamics | Enspryng®, a satralizumab formulation developed by Chugai Pharmaceutical and Roche,[L15536] utilizes a novel "recycling antibody technology" whereby the association of satralizumab to IL-6 receptors occurs in a pH-dependent manner.[A218551] Satralizumab-bound IL-6 receptors are taken up into cells and transported into endosomes, a relatively acidic environment in comparison to plasma (pH 5.5-6.0 vs. pH 7.4) - this decrease in pH allows satralizumab to dissociate from the IL-6 receptor and be recycled back into the plasma, where it can bind to another IL-6 receptor and repeat the process.[A218551] Satralizumab has been associated with an increased risk of infection, including serious and potentially fatal infections. It should not be administered to patients with active infections, including localized infections, until the infection resolves, and is contraindicated for use in patients with active hepatitis B or tuberculosis.[L15536] |
| Mechanism of Action | Interleukin-6 (IL-6) is a pro-inflammatory cytokine[A218546] which has been implicated in the pathogenesis of NMOSD.[A218551] The inflammatory cascade triggered by IL-6 signaling is thought to result in the differentiation of T-cells into pro-inflammatory TH17 cells[A218551] and the differentiation of B-cells into plasmablasts producing AQP4 autoantibodies.[A218551,A218546] IL-6 may also play a role in increasing the permeability of the blood-brain barrier, thereby allowing penetration of autoantibodies and pro-inflammatory mediators into the central nervous system.[A218551,A218546] Satralizumab is a humanized monoclonal antibody targeted against human IL-6 receptors.[L15536] It binds to soluble and membrane-bound IL-6 receptors and prevents the signaling cascade, and subsequent pro-inflammatory effects, associated with its binding to endogenous IL-6. |
| Toxicity | There is no data regarding overdose of satralizumab. No serious adverse effects were noted in healthy adults receiving a single dose of 240mg subcutaneously in clinical trials.[L15546] Patients experiencing a suspected overdose should be treated with symptomatic and supportive measures as clinically indicated. |
| Metabolism | While the metabolism of satralizumab has not been studied directly,[L15536] monoclonal antibodies as a class are principally cleared by catabolism.[L15536,A216712] |
| Absorption | The Cmax and AUC at steady-state, achieved after an 8-week loading period, were approximately 31.5 mcg/mL and 737 mcg.mL/day, respectively.[L15536] Average Ctrough concentrations were approximately 19 mcg/mL.[L15546] The bioavailability of satralizumab following subcutaneous injection has been reported to be between 78.5% and 85%.[L15536,L15546] |
| Satralizumab is subject to biphasic distribution - the estimated volume of distribution for the central and peripheral compartments are 3.46 L and 2.07 L, respectively.[L15546] |
| Clearance | The total clearance of satralizumab is concentration-dependent and is estimated to be 0.0601-0.0679 L/day.[L15536,L15546] The inter-compartmental clearance was 0.336 L/day.[L15536] |
| Categories | Proteins |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Interleukin-6 receptor subunit alpha |
| Brand Name | NA |
| Company | NA |
| Brand Description | NA |
| Prescribed For | NA |
| Chemical Name | NA |
| Formulation | NA |
| Physical Appearance | NA |
| Route of Administration | NA |
| Recommended Dosage | NA |
| Contraindication | NA |
| Side Effects | NA |
| Useful Link 1 | Link |
| Useful Link 2 | NA |
| Remarks | NA |