may edition file

improved response to omalizumab.
A 2003 analysis of pooled clinical
trial data reported a malignancy risk of
0.5% in omalizumab-treated patients.
Ligelizumab
Currently in development, ligelizumab
is a humanized anti-IgE monoclonal
antibody that binds circulating IgE. In
a phase 1 study, ligelizumab has been
shown to be more potent at suppressing
free IgE and IgE bound to mast cells and
basophils than omalizumab.
In a phase 2 double-blind parallelgroup
trial in 37 adults with mild allergic
asthma, ligelizumab elicited a 3-fold
greater provocative concentration of
allergen, causing a 15% decrease in
FEV1 compared with omalizumab and
16-fold greater than placebo at 12
weeks. Ligelizumab was administered
subcutaneously every 2 weeks. So far,
no studies have been done in children
or adolescents, and there is no data on
phenotypic response.
Mepolizumab
Mepolizumab targets IL5, a cytokine
that promotes both the activation
and longevity of eosinophils. The
Mepolizumab as Adjunctive Therapy in
Patients with Severe Asthma (MENSA)
study randomised 576 adolescents and
adults with severe eosinophilic asthma
found that asthma exacerbations
requiring oral corticosteroids (OCS) were
reduced 47% and 53% with IV and SC
mepolizumab compared with placebo,
respectively. Asthma exacerbations
requiring an ED visit were reduced 32%
and 61% with intravenous (IV) and
subcutaneous (SC) mepolizumab.
The 3 randomized controlled trials
included only patients with eosinophilic
asthma on the basis that an antibody
that reduces eosinophil levels would be
most effective in eosinophilic asthma.
Mepolizumab has been shown to
decrease eosinophil counts in both
serum and sputum.
There are no studies on children
above 12 years old, as of now, although
many studies included adolescents.
Mepolizumab is approved by USFDA
as add-on maintenance therapy in
patients who are 12 years and older
with eosinophilic asthma.
Reslizumab
Two randomised, double-blind, placebocontrolled
trials (RDBPCT) have been
conducted on reslizumab in adolescents
and adults with eosinophilic asthma.
A phase 3 trial of 374 adolescents
and adults aged 12–75 years with
inadequately controlled eosinophilic
asthma. This study noted improved
asthma control compared with placebo.
However, the quality of life measure
trended to improve in the 0.3mg/
kg dose of reslizumab but was only
significant for the higher dose.
Two duplicate RDBPCTs (phase
3) in adolescents and adults with
uncontrolled eosinophilic asthma with
serum eosinophils =400 cells/µL on
medium-to-high dose ICS therapy
noted a significant reduction in asthma
exacerbation frequency as well as
improvements in time to exacerbation,
asthma control, and quality of life
As with mepolizumab, the presence
of eosinophilia as a biomarker for
reslizumab efficacy was demonstrated
in an RDBPCT of reslizumab in adult
asthmatics, which demonstrated no
clinically significant effect on either lung
function or symptom control in patients
unselected for baseline eosinophil levels.
Reslizumab has been shown to
decrease blood eosinophil counts,
but studies are not available to show
differentiation between responders and
One of these phenotypic pathways is thought to be type 2
pathway — T helper 2 (Th2). About half of the individuals with
severe asthma exhibit the type 2 phenotype, with increase in
Th2 cells. There is an increase in the number of CD4+ T cells,
predominantly TH2 cells, in the airways of asthmatic patients,
whereas in normal airways, TH1 cells predominate. TH2 cells
have a central role in asthmatic inflammation. Also called the
“atopic” pathway, it refers to a hypersensitive reaction to an
allergen. Patients with typ2 phenotype release cytokines such
as interleukin [IL]-4, IL-5, IL-13, which drive immunoglobulin E
(IgE) production.
Targeting the cause
The majority of asthma patients are also allergic. IgE, the
antibody intimately involved in allergic responses, is the target
of omalizumab, the first approved monoclonal antibody
treatment for asthma.
“Since omalizumab was first introduced to the United
States market in 2003, it, and other more recent biologics
for asthma, have made a tremendous difference in the lives
of many asthmatics. Their impact can be likened to the
introduction of the combination of inhaled steroids and longacting
beta agonists in the 1990s, which allowed a number
of asthmatics to attain greater control of their asthma and a
number of severe asthmatics to get off of systemic steroids,”
says Dr Andy Nish, MD Fellow of American Academy of
Allergy, Asthma & Immunology (FAAAAI), USA.
The asthma biologic drug research pipeline today contains
12% monoclonal and 17% non-monoclonal antibodies.
Some groups of white blood cells, such as eosinophils,
May 2019 / FUTURE MEDICINE / 19