Most asthmatic patients have elevated circulating IgE
concentrations when levels are adjusted for age
IgE is produced by B lymphocytes
Omalizumab is a recombinant
humanized antibody of IgG1k
subclass targeted against IgE.
Approved by FDA on June 2003 for
moderate to severe asthma.
1) inhibits the binding of IgE to mast cells and
2) inhibits the activation of IgE already bound to mast
cells and thus prevent their degranulation.
3) down-regulates Fc€R-1 receptor present on mast
cells and basophils.
Slowly absorbed, Bioavailability = 60 %
Peak serum concentration is reached in 7 to 8 days
Volume of Distribution = 78 +/- 32ml/kg
Elimination of Omalizumab - IgE complexes occur in liver
and reticuloendothelial system and primarily excreted via
Elimination half-life is 26 days
A/E – Injection site reactions, headache, URTI,
Indications – Moderate to severe allergic asthma
Pts with severe concomitant allergic rhinitis
Considered as an add-on therapy to reduce or
discontinue treatment with oral corticosteroids .
Reduce asthma exacerbations.
Can’t be used as a rescue medication
Dose of 150 to 375 mg subcutaneously every 2 to 4 weeks
Dose determined by levels of serum IgE
Should be treated for a minimum of 12 weeks
Pregnancy - Category B
Lactation - caution should be exercised
PATIENT’S SELECTION FOR OMALIZUMAB THERAPY
Multiple documented severe asthma exacerbations.
Symptomatic despite high dose ICS and LABA therapy.
Frequent daytime symptoms or night-time awakenings.
Reduced lung function (FEV1 < 80%)
Body weight between 20-150 Kg and total IgE 30-1500 IU/ml
Trials are in progress for
- Peanut allergy, Latex allergy
- Atopic dermatits
Chronic idiopathic urticaria…
CONTRAINDICATIONS: Hypersensitivity reaction
Can be safely used in conjunction with inhaled
corticosteroids, inhaled beta agonists and oral
No formal drug interaction studies have been
performed with omalizumab.
Other MONOCLONAL ANTIBODIES
In Asthma Therapy
Anti TNF-α MAb
AntiTGF-β MAb − Fresolimumab
MEPOLIZUMAB (Anti IL -5Ab)
IL -5 -- cytokine in eosinophil function at sites of
Recent studies confirm that in patients with
eosinophilic asthma, mepolizumab therapy had
some clinical benefit.
However, many patients with asthma do not have
eosinophilia, and even in patients with eosinophilic
asthma, mepolizumab had no effect on other
physiological and clinical factors.
Anti TNF- alpha in Asthma Therapy
Infliximab - occurrence of neutralizing antibodies
against is a common event,
may compromise drug efficacy.
Incidence of anti-TNF induced tuberculosis in treated
Studies with golimumab did not demonstrate a
favorable risk– benefit profile
Anti-TGF beta MAb
Neutralisation of TGF-b1 with specific antibody had
no significant effect on airway inflammation and
It suppressed pulmonary fibrosis.
A mutated interleukin- -4
binds to IL -4Rα and blocks the effects of both IL- 4 and
A phase II trial in mild to moderate asthmatics
showed that inhaled pitrakinra reduced the late phase
decline in lung function.
Other potential Mabs in Asthma
A phase 1 study evaluating the pharmacokinetics,
safety and tolerability of a human IL -13 antibody
(CAT- 354) revealed an acceptable safety profile.
Specific inhibition of tissue kallikrein 1 with a human
monoclonal antibody(DX- 2300 ) revealed a potential
in vitro and in vivo role in airway diseases.
Other potential Mabs in Asthma
A Mab against TIM- 1 (Tcell Immunoglobulin Mucin
gene) protein influenced activated T cells and
blocked the development of disease in a humanized
mouse model of allergic asthma suggesting that it
may provide potent therapeutic benefit in asthma.
Limitations of Use of MAbs in Asthma
Host anti-drug responses limiting ongoing therapy
Limitations in current concepts of molecular
pathogenesis of disease
Omalizumab is the only monoclonal
antibody to date that has been found to be
effective and approved by both the FDA and
European Medicines Agency (EMEA) for the
treatment of difficult allergic asthma.
Bousquet J,et al. Expert Opin Biol Ther 2012;8(12):1921- 8