| Identification | Back Directory | [Name]
OMALIZUMAB | [CAS]
242138-07-4 | [Synonyms]
Xolair
OMALIZUMAB
Omalizumab - buffer solution
Immunoglobulin G1,anti-(human immunoglobulin E Fc region) (human-mouse monoclonal E25 clonepSVIE25 g-chain), disulfide withhuman-mouse monoclonal E25 clone pSVIE25 k-chain, dimer (9CI) | [MDL Number]
MFCD07785486 |
| Hazard Information | Back Directory | [Description]
Omalizumab is a recombinant humanized construct of murine IgG1k monoclonal
antibody introduced for the treatment of allergic asthma. It forms
complexes with free, circulating serum IgE, which results in the inhibition of binding
of IgE to the high-affinity IgE-receptor (FCeRI) on the surface of mast cells and
basophils. Reduction in surface-bound IgE on FceRI-bearing cells limits the degree
of release of mediators of the allergic response. Omalizumab is produced by a
Chinese hamster ovary cell suspension culture in a nutrient medium containing the
antibiotic gentamicin. The recommended dosage is 150–375 mg administered
subcutaneously every 2 or 4 weeks. Omalizumab has an average absolute
bioavailability of 62% and an average terminal half-life of 26 days. Following a
single SC dose, omalizumab is absorbed slowly, reaching peak serum concentrations
after 7–8 days. However, serum levels of free IgE begin to decline in a dosedependent
manner within an hour after the first injection and typically lead to ＞96%
reduction in free IgE concentrations. The omalizumab-IgE complexes have a longer half-life and are eliminated more slowly than free IgE. After 16 weeks of dosing,
total serum IgE (free plus bound IgE) is five times higher than pretreatment levels.
Clearance of the omalizumab-IgE complexes occurs via the Fcg receptors
reticuloendothelial system. The efficacy and safety of omalizumab in the treatment
of inhaled corticosteroid-dependent (ICS) asthma was evaluated in a 28-week doubleblinded,
placebo-controlled clinical study, which entailed co-administration of ICS
for 16 weeks, followed by a gradual reduction in ICS dose over 12 weeks. A
significant reduction in steroid dose with fewer exacerbations during steroid
withdrawal phase was noted and more subjects receiving omalizumab were able to
discontinue their ICS than in the placebo group (39.6 vs 19.1%, respectively;
p ＜0.001). Omalizumab was well tolerated and the most common adverse effects
were arthralgia, generalized pain, leg pain, and injection-site reactions. | [Originator]
Genentech (US) | [Uses]
Treatment of atopic disease (asthma; rhinitis) (monoclonal antibody). | [Brand name]
Xolair (Genentech). | [Mechanism of action]
Additional amino acid
sequences have been incorporated into the antibody so that a humanized product resulted that
only differs by 5% nonhuman amino acid residues.
In vitro, omalizumab has been shown to complex with free IgE, forming trimers consisting of a 2:1
complex of IgE to omalizumab or a 1:2 complex of IgE to omalizumab. In addition, larger
complexes also are formed, consisting of a 3:3 ratio of each. Omalizumab does not
bind to IgE already bound to mast cells and, therefore, does not cause the degranulation that
might be expected from such interaction. Thus, omalizumab effectively neutralizes free IgE and,
aside from the obvious decrease of available IgE, also causes the down-regulation of FcεRI
receptors on the mast cell surface, resulting in a decrease of IgE bound to the mast cell. | [Pharmacokinetics]
The bioavailability after subcutaneous administration is 62%, with slow absorption resulting in
peak serum levels in 7 to 8 days from a single dose. Steady-state plasma concentration is
reached in 14 to 29 days with multiple dosing regimens. The elimination of omalizumab is not
clearly understood; however, studies have determined that intact IgE is excreted via the bile and
that omalizumab:IgE complexes are cleared faster than uncomplexed omalizumab and slower than
free IgE. This means that over time, total IgE concentrations (free and complexed IgE) increase,
because the complex is cleared more slowly. The metabolism of omalizumab is not known, and
the clearance of the complex is similar to the liver elimination of another immunoglobulin, IgG.
The reticuloendothelial system degrades IgG, and it is believed that the same process occurs for
the omalizumab:IgE complex. | [Clinical Use]
The clinical role for omalizumab is in the treatment of allergic asthma. It is approved for the
treatment of adults and adolescents 12 years of age and older whose symptoms are not
controlled with inhaled glucocorticoids and who have a positive skin test for airborne allergens. |
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