Sapelizumab
Sapelizumab Uses, Dosage, Side Effects, Food Interaction and all others data.
Sapelizumab 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. Sapelizumab 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. 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. Sapelizumab 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, is uniquely formulated with "recycling antibody technology" whereby the association of satralizumab to IL-6 receptors occurs in a pH-dependent manner - 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.
Sapelizumab was first approved for use in Canada in June 2020 for the treatment of AQP4 antibody-positive patients with NMOSD. It received subsequent approvals in Switzerland and Japan, and was approved for use by the FDA in August 2020, becoming the 3rd treatment to receive FDA approval for NMOSD (after eculizumab in June 2019 and inebilizumab in June 2020).
| Trade Name | Sapelizumab |
| Availability | Prescription only |
| Generic | Satralizumab |
| Satralizumab Other Names | Sapelizumab, Satralizumab, satralizumab-mwge |
| Related Drugs | Soliris, eculizumab, Uplizna, Enspryng |
| Type | |
| Weight | 143000.0 Da |
| Groups | Approved |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Sapelizumab is a subcutaneously injected anti-IL-6 receptor monoclonal antibody for the treatment of neuromyelitis optica spectrum disorder (NMOSD).
Sapelizumab is indicated for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adult patients who are anti-aquaporin-4 (AQP4) antibody positive. In Canada, it is also used in adolescent patients for the same indication.
Sapelizumab is also used to associated treatment for these conditions: Neuromyelitis Optica Spectrum Disorder
How Sapelizumab works
Interleukin-6 (IL-6) is a pro-inflammatory cytokine which has been implicated in the pathogenesis of NMOSD. The inflammatory cascade triggered by IL-6 signaling is thought to result in the differentiation of T-cells into pro-inflammatory TH17 cells and the differentiation of B-cells into plasmablasts producing AQP4 autoantibodies. 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.
Sapelizumab is a humanized monoclonal antibody targeted against human IL-6 receptors. 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. Patients experiencing a suspected overdose should be treated with symptomatic and supportive measures as clinically indicated.
Food Interaction
No interactions found.Volume of Distribution
Sapelizumab 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.
Elimination Route
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. Average Ctrough concentrations were approximately 19 mcg/mL. The bioavailability of satralizumab following subcutaneous injection has been reported to be between 78.5% and 85%.
Half Life
The terminal half-life of satralizumab is approximately 30 days (range 22-37 days).
Clearance
The total clearance of satralizumab is concentration-dependent and is estimated to be 0.0601-0.0679 L/day. The inter-compartmental clearance was 0.336 L/day.
Elimination Route
Monoclonal antibodies are typically eliminated via uptake into cells and subsequent catabolism via lysosomal degradation. Due to their large size, they are only eliminated renally under pathologic conditions.
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