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| Primary information |
|---|
| ID | 12910 |
| Therapeutic ID | Th1368 |
| Protein Name | Reslizumab |
| Sequence | NA
|
| Molecular Weight | 147000 |
| Chemical Formula | NA |
| Isoelectric Point | NA |
| Hydrophobicity | NA |
| Melting point | NA |
| Half-life | The half-life is approximately 24 days [FDA Label]. |
| Description | Reslizumab is a humanized interleukin-5 (IL-5) antagonist monoclonal antibody (IgG4 kappa) that is produced by recombinant DNA technology in murine myeloma non-secreting 0 (NS0) cells. IL-5 is a pro-inflammatory cytokine that is responsible for the growth and differentiation, recruitment, activation, and survival of eosinophils [FDA Label]. Elevated levels of eosinophils increase the risk for asthma exacerbations, including both allergic forms and nonallergic forms of asthma where eosinophilia is prominent. By targeting the IL-5 and disrupting its signalling pathways, reslizumab aims to inhibit eosinophil maturation and promote programmed cell death [A31578]. Asthma is a chronic respiratory disease that causes inflammation in the lungs with asthma attacks that lead to severe breathing difficulties. Patients often experience persistent or exacerbating symptoms overtime despite conventional first-line therapies available. Inflammation-predominant asthma, which is chatacterized by eosinophilic infiltration of airway mucosa and elevated levels of eosinophils in the blood, sputum and BAL fluid, is associated with an increased risk for recurrent exacerbation and asthma-related hospitalizations [A31579]. In four double-blind, randomized, placebo-controlled trials in patients with severe asthma on currently available therapies, patients receiving reslizumab had fewer asthma attacks, and a longer time to the first attack compared to patients receiving placebo [FDA Label, A31579]. In addition, a significant improvement in lung function was seen, as measured by the volume of air exhaled by patients in one second [L1133]. Studies demonstrated that reslizumab was not effective in various asthma outcomes in patients without eosinophilia [A31577]. Reslizumab was developed by Teva Pharmaceuticals. Approved by the FDA in March 2016, reslizumab is marketed under the brand name Cinqair for intravenous injection. It is injected once every four weeks via intravenous infusion. Cinqair is indicated as an add-on maintenance therapy for adults with severe asthma with an eosinophilic phenotype. It is approved for patients who have a history of severe asthma attacks (exacerbations) despite receiving their current asthma medicines. Reslizumab is marketed as Cinqaero in Europe. |
| Indication/Disease | Indicated for the add-on maintenance treatment of patients with severe asthma aged 18 years and older with an eosinophilic phenotype. |
| Pharmacodynamics | A reduction in blood eosinophil counts was observed in clinical studies following an initial infusion of 3 mg/kg reslizumab and was maintained through 52 weeks of treatment with no signs of tachyphylaxis. Greater reductions of blood eosinophils were observed in subjects with higher reslizumab serum concentrations. This effect was independent of the presence of treatment-emergent anti-reslizumab antibodies [FDA Label]. |
| Mechanism of Action | Reslizumab an interleukin-5 (IL-5) antagonist (IgG4, kappa) that binds to IL-5 with a dissociation constant of 81 pM. IL-5 is a proinflammatory cytokine responsible for the terminal maturation of eosinophils and increases chemotaxis, endothelial adhesion, activation and survival of eosinophils. Eosinophils are known to play a central role in the pathophysiology of many patients with asthma; upon activation, eosinophils release leukotrienes, platelet activation factor, major basic protein, eosinophil cationic protein, eosinophil peroxidase, eosinophil-derived neurotoxin, and other cytokines that are cytotoxic to the bronchial epithelium and lead to airway inflammation and bronchospasm [A31577]. IL-5 production is increased by upon activation of TH2 lymphocytes after antigen exposure and IL-5 stimulates the production and maturation of eosinophil precursors in the bone marrow [A31577]. IL-5 promotes the growth and differentiation, recruitment, activation, and survival of eosinophils via interacting with the IL-5 receptor expressed on the eosinophil surface [FDA Label]. Increased production and activation of eosinophils is especially prominent in nonallergic forms of asthma [A31577]. Reslizumab is a humanized monoclonal antibody that occupies the region ERRR (glutamic acid, arginine, arginine, arginine) corresponding to amino acids 89–92 on IL-5, which is a region critical for its interaction with the IL-5 receptor on the eosinophil surface [A31577]. By binding to IL-5 and disrupting its binding to the alpha chain of the IL-5 receptor complex, reslizumab inhibits the bioactivity of IL-5 and attenuates IL-5 signaling. Blocking of IL-5 signalling thereby reduces the production and survival of eosinophils and inhibits eosinophilic-driven inflammation. |
| Toxicity | Single doses of up to 732 mg have been administered intravenously to subjects in clinical trials without evidence of dose-related toxicities. There is no specific treatment for an overdose with reslizumab. If the event of an overdose, the patient should be treated supportively with appropriate monitoring as necessary [FDA Label]. Based on the findings of a 6-month bioassay, reslizumab showed no evidence of carcinogenicity. In a fertility study, administration of reslizumab to parental mice at doses up to 50 mg/kg (approximately 6 times the MRHD on an AUC basis) had no effects on male or female mating or fertility. The malignancy risk of reslizumab in humans with effects on tumor growth is not yet established [FDA Label]. |
| Metabolism | Like other monoclonal antibodies, reslizumab is assumed to undergo enzymatic proteolysis into smaller peptides and amino acids. As reslizumab bind to the target, it is not expected to undergo a target-mediated clearance [FDA Label]. |
| Absorption | The peak serum concentrations of reslizumab were typically observed at the end of the infusion with the serum concentrations gradually declining from the peak in a biphasic manner. Following multiple doses, serum concentrations of reslizumab accumulated approximately 1.5 to 1.9-fold. Interindividual variability in peak and overall exposure across healthy individuals, patients with asthma, and other populations in pharmacokinetic studies was around 20-30% [FDA Label]. Systemic exposure to reslizumab appeared to be unaffected by the presence of treatment-emergent anti-reslizumab antibodies. |
| The approximate volume of distribution of reslizumab is 5L, suggesting minimal distribution to the extravascular tissues [FDA Label]. |
| Clearance | Reslizumab clearance was approximately 7 mL/hour [FDA Label]. |
| Categories | Antibodies |
| Patents Number | NA |
| Date of Issue | NA |
| Date of Expiry | NA |
| Drug Interaction | NA |
| Target | Interleukin-5 |
| Brand Name | Cinqair |
| Company | TEVA Canada Limited |
| Brand Description | TEVA Canada Limited |
| Prescribed For | Intravenous |
| Chemical Name | 10 mg / mL |
| Formulation | CINQAIR is contraindicated in patients who have known hypersensitivity to reslizumab or any of its excipients |
| Physical Appearance | mouth and throat pain. |
| Route of Administration | Cinqair is a monoclonal antibody that affects the actions of the body's immune system. Reslizumab works by reducing levels of a certain type of white blood cell that may contribute to the symptoms of asthma. Cinqair is a prescription medicin eused together with other medicines to help control severe... |
| Recommended Dosage | Cinqair is a prescription medicine used to treat the symptoms of Asthma. Cinqair may be used alone or with other medications. |
| Contraindication | NA |
| Side Effects | CINQAIR (reslizumab) is a humanized interleukin-5 antagonist monoclonal antibody (IgG4κ). Reslizumab is produced by recombinant DNA technology in murine myeloma non-secreting 0 (NS0) cells. Reslizumab has a molecular weight of approximately 147 kDa. |
| Useful Link 1 | Link |
| Useful Link 2 | Link |
| Remarks | NA |