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DR.

ANIMESH ARYA

1
INTRODUCTION TO ALLERGIC RHINITIS

PATHOPHYSIOLOGY, DIAGNOSIS & MANAGEMENT

NEED FOR A NEW MOLECULE


nidu

NEZACT

TAKE HOME MESSAGE


INTRODUCTION TO ALLERGIC RHINITIS

PATHOPHYSIOLOGY, DIAGNOSIS & MANAGEMENT

NEED FOR A NEW MOLECULE


nidu

NEZACT

TAKE HOME MESSAGE


Allergic rhinitis: World wide prevalence

Almost 400 million people suffer from allergic rhinitis

10-30% EUROPE 17-29%


11-63% ASIA
NORTH AMERICA

13–17%
AFRICA
10-32% AUSTRALIA
LATIN AMERICA
15%
Allergic rhinitis: Indian prevalence

Indian prevalence is about


10-30%

Chandrika , D. Allergic rhinitis in India: an overview. Int J Otorhinolaryngol Head Neck Surg. 2017 January;
3(1)(1-6)..
Allergic rhinitis and asthma

19–38%
of patients with
allergic rhinitis
Prevalence of Incidence of Countries have
Asthma Allergic rhinitis concomitant
Low <5% Indonesia, Albania, Romania, asthma
prevalence Georgia and Greece
>30% 15-20% Australia, New Zealand and
the United Kingdom
had a high prevalence of
rhinitis

Ozdoganoglu T, Songu M. The burden of allergic rhinitis and asthma. Ther Adv Respir Dis. 2012 Feb;6(1):11-23.asthma
Allergic rhinitis: Common allergens

Grass pollen House dust mite

Food allergens
Pet dander
Allergic rhinitis: sizes of common allergens
Different species of grass pollen

35 14 20
microns microns microns

House Dust Pet dander Fungi mold


mite 5-10 2-100 microns
330 microns microns

15-20
microns
Natural barrier for entry of allergens

Grass pollen Pet Dander


House dust
mite

First barrier to wide range of


inhaled challenges

• Barrier function
• Mucociliary clearance
• Antimicrobial peptides
• ROS
• Reactive nitrogen species
• Range of cytokines,
chemokines and growth
factors
Tight junctions, cell–cell adhesion complexes between
epithelial cells, are important for epithelial barrier function

Tight junctions contain three


types of transmembrane
proteins:
• Occludins
• Claudins
• Junction adhesion
molecules (JAMs)
• scaffold proteins such as
zonula occludens-1

Georas SN, Rezaee F. Epithelial barrier function: at the front line of asthma immunology and allergic airway
inflammation. J Allergy Clin Immunol. 2014 Sep;134(3):509-20..
Fukuoka A, Yoshimoto T. Barrier dysfunction in the nasal allergy. Allergol Int. 2018 Jan;67(1):18-23. 10
1. Prevalence of AR in India is 10-30%
2. Prevalence of concomitant AR and asthma is
high
◦ United airway disease concept
3. Average size of the allergen is 15-20 microns
4. Mucosal layer vis a viz ‘the tight junctions’,
forms a natural protective barrier against
entry of allergens
INTRODUCTION TO ALLERGIC RHINITIS

PATHOPHYSIOLOGY, DIAGNOSIS & MANAGEMENT

NEED FOR A NEW MOLECULE


nidu

NEZACT

TAKE HOME MESSAGE


38 year old male with a history of nasal
congestion, clear nasal discharge and
episodes of itchy/watery eyes. Symptoms for
the past five years and began after moving
from Michigan to Texas six years ago.
Symptoms mostly occur during the
January/February timeframe.

Take OTC antihistamines but only


gets minor improvement. Older brother has
asthma.

13
Allergic rhinitis: Pathophysiology
DEP (HDM) allergen impairs nasal epithelial barrier
functions
• Monolayer RPMI 2650
cells cultured in
upper wells were
treated with DEP for
24 h.
Immunostaining for
ZO-1 (A)
• Transepithelial
electric resistance
(TER) was measured
(B)
• After 24 h of DEP
treatment, RPMI 2650
cells were incubated
Immunohistochemistry analysis showed that ZO- with FITC-dextran for
1 expression in nasal epithelia was decreased by 3 h, and then culture
treatment of DEP alone for 4 days supernatants were
collected
• Fluorescence
Fukuoka A, Yoshimoto T. Barrier dysfunction in the nasal allergy. Allergol Int. 2018 Jan;67(1):18-23.
intensity in culture
Dysfunctional nasal epithelial barrier leads to increase
uptake of allergens
Mutiple disorders >> asthma,
AR, IBD, functional dyspepsia,
and atopic dermatitis have been
linked to defective or altered TJ
function
A dysfunctional epithelial
barrier might give rise to
enhanced uptake of allergens
and exogenous particles,
leading to more activation of
mast cells and nerve fibers”

Matilla P, et al. Clin and Translational Allergy 2011


Steelant B, et al. J Allergy Clin Immunol 2016; 137: 1043-
53
Vicious cycle of nasal inflammation and allergen entry
leading to dysregulation of natural protective barrier

Allergic
rhinitis

More entry of Inflammation/


allergens allergen

Damage nasal
epithelium
and impair
muco-ciliary
clearance
Allergic rhinitis: Diagnosis

SYMPTOMS DIAGNOSTIC TESTS


Rhinorrhoea
Sneezing Allergen-specific IgE in the
Nasal obstruction skin (skin tests) or
Pruritus blood specific IgE

Bousquet J, Khaltaev N, Cruz AA, Denburg J, Fokkens WJ, Togias A, et al. Allergic Rhinitis and its Impact on
Asthma (ARIA) 2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen).
Allergic rhinitis: Comprehensive management

Allergen
avoidance

Pharmacotherapy

Patient
Education Allergen
specific
immunotherapy

Bousquet J, Khaltaev N, Cruz AA, Denburg J, Fokkens WJ, Togias A, et al. Allergic Rhinitis and its Impact on Asthma
(ARIA) 2008 update (in collaboration with the World Health Organization, GA(2)LEN and AllerGen). Allergy 2008; 63(suppl
86):8-160.
Allergic rhinitis: Management
Allergen First step
avoidance

Bousquet J, Khaltaev N, Cruz AA, Denburg J, Fokkens WJ,


Togias A, et al. Allergic Rhinitis and its Impact on Asthma
(ARIA) 2008 update (in collaboration with the World Health
Organization, GA(2)LEN and AllerGen). Allergy 2008;
Summary

1. AR is an Ig E mediated disease
2. In AR there is a vicious cycle of nasal inflammation
and dysregulation of natural protective barrier
3. Allergen avoidance is the first step in the
management of allergic rhinitis
4. ARIA guidelines recommends a step wise approach
for treating AR patients
INTRODUCTION TO ALLERGIC RHINITIS

PATHOPHYSIOLOGY, DIAGNOSIS & MANAGEMENT

NEED FOR A NEW MOLECULE


nidu

NEZACT

TAKE HOME MESSAGE


23
Ratner et al. LaForce et al. Storms et al. Lumry et al.
0%
Percentage change from baseline in

-5%

-10%
-14%
1
daily TNSS

-15%
spray
-20% bid
-24%
-25%
-26%
2 2
-29%
sprays sprays
-30% 2 bid
sprays bid
-35% bid
75% of symptoms are not controlled with Azelastine
treatment
Unmet need with existing therapy
Reductions in total nasal symptom scores:
Fluticasone

US Dose ranging European grass


study pollen US Ragweed
0%
Percentage change from baseline in

-10%

-20%

-30%
daily rTNSS

-40% -46%
P < 0.001
-50%

-60% -66%
-70% P < 0.001
-80% -85%
-90% P < 0.001

25-30% of symptoms are not controlled with fluticasone


treatment
Recently recognized in
European society and ARIA
guideline

"20% of patients with


AR do not respond
properly to treatment”

Hellings and chronic rhinosinusitis: where do we stand


today? Allergy.2013 Jan;68(1):1-7
Steelant B, et al. J Allergy Clin Immunol 2016; 137: 1043-53
"20% of patients with AR do not
respond properly to treatment“

The reason for lack of response to


treatment is multifactorial, with barrier
dysfunction being one of the reasons

A dysfunctional epithelial
barrier might give rise to
enhanced uptake of allergens
and exogenous particles,
leading to more activation of
mast cells and nerve fibers”

Matilla P, et al. Clin and Translational Allergy 2011


Steelant B, et al. J Allergy Clin Immunol 2016; 137: 1043-53
………therefore, allergen
avoidance is the first and most
important step in management of
allergic rhinitis
Practical challenges with allergen avoidance measures

Washing bed sheets


Washing carpets

HEPA filter

Removal of carpets
Washing
Practical issues with allergen avoidance

Disadvantag
Advantages
es
Challenges because of outdoor allergens…….
Solution…….?
1. There are practical challenges in
implementing allergen avoidance measures
2. Outdoor allergens also remains a challenge
3. With existing therapies, reduction in
symptoms
• 25% with intra-nasal anti-histamines
• 70% with intra-nasal corticosteroids is nearly
4. Nearly 20% of the patients have uncontrolled
allergic rhinitis
5. Dysfunctional barrier with increased allergen
penetration is one of the cause
There is a need to re-inforce
and protect the natural nasal
mucosal barrier

34
INTRODUCTION TO ALLERGIC RHINITIS

PATHOPHYSIOLOGY, DIAGNOSIS & MANAGEMENT

NEED FOR A NEW MOLECULE


nidu

NEZACT

TAKE HOME MESSAGE


Nezact

Contains
• Proprietary grade of
micronized cellulose powder
of HPMC (98.5%)-active
ingredient
• Peppermint powder (1.5%)

Product characteristics:

White or pale white cellulose


powder made of vegetable
origin

36
Innovator: Registered as a Medical Device in over 50
countries

United
Kingdom
Canada
class I Russia
device
Denmark
Germany
Greece
class II N America Finland
Norway
device Belgium China
Switzerland
Spain

Bahrain
UAE
Qatar Hong Kong
Uruguay Saudi Singapore
Arabia Thailand
Brazil South
Africa

Peru
Australia

New
Zealand
Delivery system
Delivered via a bespoke puffer bottle
made of materials compliant with
③ The nozzle
pharmaceutical industry use
delivers a
fine mist of
powder All components tested for
biocompatibility meeting ISO 10993
standards
The air and
② powder
travel up
the hollow
delivery
tube to the
nozzle
When the
bottle is
squeezed,
air forces
① Nezact Intra-nasal delivery
powder up
the hollow
Chemistry

Hydroxypropylmethylcellulos
e

Semisynthetic, inert, water soluble, viscoelastic


polymers derived from cellulose

• Nezact contains HPMC of a special


grade
• Other grades of HPMC don’t produce the same 39
Mechanism of action
Extra barrier that prevents
pollen or allergens from
reaching the mucosa

Cellulose absorbs moisture


within nasal airway to form a
protective

Gel like
barrier
Airborne allergens can be
entrapped and therefore be
prevented from reacting with
receptors

BEFORE-Nezact AFTER-Nezact Emberlin JC, et al. Curr Med Res Opin 2006;
powder powder 22(2): 275-85
Andersson M. et al. Curr Med Res Opin
Mechanism of action

41
Mechanism of action

Allergic
rhinitis

More entry of Inflammation/


allergens allergen

Damage nasal
epithelium
and impair
muco-ciiliary
clearance
Mechanism of action

100x
magnification
Pharmacokinetics/pharmacodynamics

Distribution
Time to onset of Cellulose gel is
considered inert and
action
does not penetrate the
3 mins
dermal layer of the skin.
There is no systemic
absorption

Duration of action Drug interactions


4-6 hours Cellulose is inert.
Hence, there will be no
drug interaction

44
Safety

GENERALLY
GRA RECOGNIZE
D AS SAFE
S
There are no contraindications
for use
Usage in special population

Pregnancy Breast feeding


SAFE TO USE

Has been studied in children Elderly


above 18 months of age 46
All forms of allergic rhinitis

In symptomatic patients (intermittent and persistent):


• Mild disease
• As a monotherapy to achieve optimal symptom
control
• Moderate-severe
• As an add-on to INCS and/or Intra-nasal anti-
histamine/oral anti-histamine

In asymptomatic patients (intermittent and persistent):


As a prophylactic monotherapy to prevent patients from
developing symptoms

47
1. Proof of concept study
2. Pilot study
3. Clinical efficacy study
4. Proof of gel like barrier concept
5. Studies in persistent perennial rhinitis
6. Monotherapy
7. Studies as on add-on therapy
8. Studies as on add-on to nasal sprays
9. Studies in paediatric population

48
1. Proof of concept study
2. Pilot study
3. Clinical efficacy study
4. Proof of gel like barrier concept
5. Studies in persistent perennial rhinitis
6. Monotherapy
7. Studies as on add-on therapy
8. Studies as on add-on to nasal sprays
9. Studies in paediatric population

49
During pollen season

Design: Open label, HPMC powder (1 puff/nostril x 3 times)


single arm study

Day 0 6 weeks
Population:102
volunteers (36 M; 66
F) suffering from
seasonal AR in UK
• Effectiveness of pharmaceutical treatment 5-
Evaluation: point scale
• Day/time for recovery
Proof of concept study: Results
Use of cellulose powder for the treatment of seasonal allergic rhinitis.
Josling, Steadman. Adv Ther. 2003;20(4):213–219.

Treatment Male Female


Volunteer Volunteers
s

Beconase® (steroid nasal inhaler) Glaxo Smith 3.0 3.1


Kline, UK
Sodium cromoglycate (antihistamine nasal inhaler) 1.3 2.1
-Various
generic manufacturers
Opticrom® (eyedrops) Aventis Pharma, UK 1.5 2.0
Clarityn® (oral tablets) Schering Plough, UK 2.0 2.2
Zirtek® (oral tablets) Glazo Smith Kline, UK 1.1 1.8
1 = not
Pinion® (oral tablets and liquid) Stafford Miller, UK 1.3 1.8 effective
Telfast® (oral caplet) HMR, UK 2.0 1.8 5 = very
Assessment of pharmaceutical treatment
Natural cellulose powder 3.8 3.9 effective

Score represents 77% reduction in


symptoms

Time to onset of action- 6 mins


1. Proof of concept study
2. Pilot study
3. Clinical efficacy study
4. Proof of gel like barrier concept
5. Studies in persistent perennial rhinitis
6. Monotherapy
7. Studies as on add-on therapy
8. Studies as on add-on to nasal sprays
9. Studies in paediatric population

52
Study done during
Gp A pollen season
Design: Double blind HPMC powder (N=47)
randomized placebo
controlled study in UK
Age and gender
Gp B matched

Population: 97 adults Placebo (N=50)


with 2 year history of
SAR (2004).
Conventional Day 0 2 7 weeks
medication used for 1
rescue only

Evaluation : • Difference in amount and type of rescue


medication
Pilot study: Usage of rescue medication
A double blind, placebo controlled trial of inert cellulose powder for the relief of
symptoms of hay fever in adults
Emberlin JC, Lewis RA. Curr Med Res Opin. 2006;22(2):275–285

60

50 HPMC powder Placebo

40
Percentage of participants

30 Significant differences in
57% of the
20
the amount of rescue subjects
10
medication usage controlled
(P<0.05) with HPMC
0
alone

Rescue medication usage during study period


Pilot study: Usage of rescue medication
A double blind, placebo controlled trial of inert cellulose powder for the relief of
symptoms of hay fever in adults
Emberlin JC, Lewis RA. Curr Med Res Opin. 2006;22(2):275–285

Rescue medication usage during study period

Conclusions:
Cellulose powder reduces the need to take
rescue medication for the symptoms of
hay fever
1. Proof of concept study
2. Pilot study
3. Clinical efficacy study
4. Proof of gel like barrier concept
5. Studies in persistent perennial rhinitis
6. Monotherapy
7. Studies as on add-on therapy
8. Studies as on add-on to nasal sprays
9. Studies in paediatric population

57
Study done during
Gp A spring season
Design: Double blind HPMC powder (N=54)
randomized placebo
controlled study in
Ukraine
Gp B

Placebo (N=53)
Population: 107 adults
with grass pollen
allergy. Conventional Day 0 2 4
medication used for 1 weeks
rescue only
Daily symptom score (scale 1-6)
• Nasal
Evaluation : • Ocular
• Bronchial
Clinical efficacy study: Results
A nasally applied cellulose powder in seasonal allergic rhinitis in adults with
grass pollen allergy: a double-blind, randomized, placebo-controlled, parallel-
group study
Aberg N, Ospanova ST, Nikitin NP Emberlin J, Dahl Å. Int Arch Allergy Immunol. 2014;163 (4):313–318..

Total of symptom scores for 4 weeks


Question Placebo (n = Active (n = p value
Sum of nasal symptoms day by day
53) 54)
Sneezing 2.31 1.65 <0.001

Runny nose 2.37 1.75 <0.001

Blocked nose 2.32 1.76 <0.001

Eye symptoms 2.18 1.59 <0.001

Lower airways 1.92 1.44 <0.001

Sum of nasal 6.99 5.16 <0.001


symptoms
Sum of all 11.1 8.19 <0.001
symptoms

Global opinion about the effect of treatment

Scoring Opinion Placebo, n Active, n


1 = no trouble; 6 = very much trouble No effect 28 (52.8%) 4 (7.4%)

• ~50%
Good effect 12 (22.6%) 32 (59.3%)

Very good effect 1 (1.9%) 15 (27.8%)

reduction :
Don’t know 12 (22.6%)

Group differences, p < 0.001.


3 (5.6%)

• Nasal (p<0.001)
1. Proof of concept study
2. Pilot study
3. Clinical efficacy study
4. Proof of gel like barrier concept
5. Studies in persistent perennial rhinitis
6. Monotherapy
7. Studies as on add-on therapy
8. Studies as on add-on to nasal sprays
9. Studies in paediatric population

60
Proof of gel like barrier concept
Study Proof of concept that HPMC gel delays Der p1 diffusion in vitro
Diethart B, et al. Natural Science 2010: 2: 79-84

Allergen
151 ng/ml Der
P1

AGA AGA
R R

HPMC CONTRO
AGAR: Simulates the nasal Measure: L
mucosa Amount of allergen penetrating
through the AGAR gel at
different time points by ELISA
technique
Proof of gel like barrier concept
Study Proof of concept that HPMC gel delays Der p1 diffusion in vitro
Diethart B, et al. Natural Science 2010: 2: 79-84

Time 15 min 30 min 60 min 180 min 360 min


(min)
Control 72.2% No 100%
value
HPMC 0.76% 1.04% 5.94% 8.72% 14.1%

Conclusions:
• Diffusion of allergen through Nezact showed a significant reduction
at all time points
• After 360 mins only 14% had diffused through
• Nezact forms a gel barrier which prevents allergens from diffusion
Clinical studies

1. Proof of concept study


2. Pilot study
3. Clinical efficacy study
4. Proof of gel like barrier concept
5. Studies in persistent perennial rhinitis
6. Monotherapy
7. Studies as on add-on therapy
8. Studies as on add-on to nasal sprays
9. Studies in paediatric population

63
Period 1 Period 2

HPMC powder HPMC powder

N=15

Placebo Placebo

Wash
with 2.5 Drug Same procedure
ml saline applicati Within 7
on days
• Der p1 Skin Baseline Allergen
24 hrs
test challeng
positive e Evaluation:
• Persistent
symptoms Total symptoms score
for last 2 Peak nasal inspiratory flow
yrs
Peak nasal expiratory flow
Effectiveness against persistent perennial rhinitis:
Results
A double blind, placebo-controlled crossover trial of cellulose powder by nasal
provocation with Der p1 and Der f1
Emberlin JC, et al. Curr Med Res Opin 2007; 23(10): 2423-2431

0 = absent Total symptom


5 = very severe score
Mean difference of
8.8 vs 15 (P≤
0.05)

PNIF an PEF:
Mean
difference in
favour of
Nezact(P≤
0.05)

Conclusions:
Nezact significantly reduces persistent perennial rhinitis
1. Proof of concept study
2. Pilot study
3. Clinical efficacy study
4. Proof of gel like barrier concept
5. Studies in persistent perennial rhinitis
6. Monotherapy
7. Studies as on add-on therapy
8. Studies as on add-on to nasal sprays
9. Studies in paediatric population

66
Design: Open label,
single arm study

HPMC powder (1 puff/nostril once in the


morning)
Population:40
volunteers suffering
Day 1
from perennial AR 3 weeks 6 weeks
Discontinue
current
medication
5-point symptom relief
Evaluation: score
50%
42.50%  5 – complete relief,
40% 35%  4 – major relief,
Decongestan
 3 – light, but noticeable
ts
30% allergy symptoms
20%  2 – allergy symptoms
20%
Corticosteroi apparent with periodic
10% ds flare ups
2.50%  1 – allergic rhinitis with
0% complete symptoms
Baseline medication
Scale 1 Scale 2 Scale 3 Scale 4 Scale 5 % scoring
complete
or major relief
(4,5)
Baseline - 4 (10%) 16 (40%) 14 (35%) 6 (15%) 0 (0%) 15%
before
treatment
3 weeks 1 (2.5%) 5 (12.5%) 16 (40%) 13 (32.5%) 5 (12.5%) 45%

6 weeks 1 (2.5%) 2 (5%) 6 (15%) 20 (50%) 11 (27.5%) 77.5%


Table 1 shows number of patients during each time period and their reported score (percent of total participants in
parenthesis). 3 scale 2 scale 1 scale 0 scale Mean
improvement improvement improvement improvement improvement

3 weeks 0% 5% 80% 15% 0.9 scales


6 weeks 7.5% 35% 47.5% 10% 1.4 scales
Table 2 shows the percent of participants that experienced improvement.

Conclusions
• After 3 weeks of use, 85% of participants realized
improvement in their allergy symptoms
• After 6 weeks of use, 90% of participants realized
improvement in their symptoms
1. Proof of concept study
2. Pilot study
3. Clinical efficacy study
4. Proof of gel like barrier concept
5. Studies in persistent perennial rhinitis
6. Monotherapy
7. Studies as on add-on therapy
8. Studies as on add-on to nasal sprays
9. Studies in paediatric population

69
Design: comparator HPMC powder + standard therapy (N=20)
study, 2:1 study
design

Population: 30 adults Placebo + standard therapy (10)


with moderate
intermittent AR
patients.
Pollen, ragweed and Day 0 4
weeks
sunflower allergy

Standard therapy:
cetririzine, topical
glucocorticoids
Evaluation : Symptom score
Quality of life
HPMC as an add-on to conventional therapy:
Results
The efficiency of cellulose powder extract in complex therapy of patients
with pollen allergic rhinitis.
Penechko EM, Sizyakina LP. Rossiyskiy Allergologicheskiy J. 2011;(3):101–104.

Symptom Standard Standard therapy Standard therapy Standard therapy


(points) therapy after treatment + Nezact before + Nasaleze after
before treatment treatment
treatment
Runny nose 3.1±0.3 1.7±0.5* 3.2±0.7 ***0.7±0.1**

Sneezing 2.7±0.9 1.7±0.6 2.8±0.5 ***0.7±0.3**

Itchy nose 1.5±0.1 0.8±0.1 1.9±0.2 ***0.4±0.1**

Stuffy nose 3.5±0.8 1.5±0.3* 3.3±0.5 ***0.6±0.3**

Itchy eyes 1.7±0.5 1.5±0.4 1.5±0.2 1.4±0.1

Tickle in throat 1.4±0.2 0.9±0.3 1.4±0.1 0.9±0.3

0 - Absent (no symptoms),


1 - Mild (symptoms are present, but do not affect normal life),
2 - Moderate (symptom causes discomfort but does not interfere with normal daily activity or sleep),
3 - Medium severity (symptom causes significant discomfort, interferes with normal daily activity or
sleep),
4 - Severe (symptom occurs so strongly that it is necessary to change the course of treatment and
use stronger
medications).

71
HPMC as an add-on to conventional therapy:
Results
The efficiency of cellulose powder extract in complex therapy of patients
with pollen allergic rhinitis.
Penechko EM, Sizyakina LP. Rossiyskiy Allergologicheskiy J. 2011;(3):101–104. 0 - No adverse effects,
Standard therapy 1 - Almost no adverse effects
3 2 - Mild adverse effects,
2.5 3 - Moderate adverse effects,
4 - Strong adverse effects,
2 5 - Very strong adverse
effects,
1.5 6 - Severe adverse effects,
both before and after
1 treatment.
0.5
0
Statistically
significant
difference in
favour of HPMC
(P<0.05)

Quality of life assessment

Conclusions
• Nezact as part of the complex treatment for intermittent allergic rhinitis
is beneficial
Study done during
Gp A pollen season
Design: Open label HPMC powder+ oral cetirizine
trial
N=74
Gp B
Population: 74
subjects with mild SAR Placebo + oral cetirizine

Evaluation : 5-point
symptom
scale Day 0 5 10 days
Conclusion
s:
Percentage of subjects on cetirizine+ HPMC
scoring ‘major’ or ‘complete relief’ was more
when compared to cetirizine alone
1. Proof of concept study
2. Pilot study
3. Clinical efficacy study
4. Proof of gel like barrier concept
5. Studies in persistent perennial rhinitis
6. Monotherapy
7. Studies as on add-on therapy
8. Studies as on add-on to nasal sprays
9. Studies in paediatric population

74
Concept of muco-adhesion leading to
synergism

Conventiona
l nasal spray

75
Concept of muco-adhesion leading to
synergism

Application of
Nezact

‘Sealing ’ effect of
the intra-nasal
spray to the nasal
mucosa will create a
synergism

More drug is
available at the site
of action

76
Gp A
1 puff of
Design: Double blind Oxymetazoline rescue
oxymetazoline+ 1
randomized placebo medication only
puff of HPMC powder
controlled study
Population: 40 adults
with perennial Gp B
1 puff of
persistent AR Oxymetazoline rescue
oxymetazoline+ 1
medication only
puff of placebo

Day 1 7 15 days

Evaluation : PNIF after 360 mins on Day 1 and 8; Day 15


Symptom score using visual analog scale

77
P= P=
0.042 0.006

- - - Placebo - - - Placebo Nezact


Nezact

Changes in PNIF: Day Changes in PNIF: Day


1 8

78
- - - Placebo
Nezact
- - - Placebo
Nezact

Baseline PNIF at each visit


Baseline PNIF at each visit

Conclusions
• HPMCenhances the decongestant effect of nasal oxymetazoline
in patients with allergic rhinitis.
• The effect carries over for another week after its discontinuation
1. Proof of concept study
2. Pilot study
3. Clinical efficacy study
4. Proof of gel like barrier concept
5. Studies in persistent perennial rhinitis
6. Monotherapy
7. Studies as on add-on therapy
8. Studies as on add-on to nasal sprays
9. Studies in paediatric population

80
Pediatric population
A nasally applied cellulose powder in seasonal allergic rhinitis
(SAR) in children and adolescents; reduction of symptoms and
relation to pollen load.
Design: Double blind randomized placebo controlled study in Sweeden
Aberg N, Dahl A, Benson M. Pediatr Allergy Immunol. 2011;22(6):594–599

(2009) for 4 weeks Significant difference in favour


Population: of Nezact (P=0.033)
53 children (8-18
yrs) with birch
pollen allergy
Sneezing
running nose
Treatment arms: blocked nose
• 25 children in
Nezact group+
Desloratidine
• 28 children in Scoring
1 = no trouble;
control group+ 6 = very much
Desloratidine trouble
Sum of Nasal scores

Conclusions:
HPMC significantly reduces nasal symptoms in
Allergic conjunctivitis 50% 53% 48% 57%
Х Х

Pediatric population
efficacy of the Inert Cellulose Powder in children with AR during the first two weeks (р<0,05)
Х Х Family history of allergic illnesses 20 (66,7%) 22 (73,3%) 15 (75,5%) 20 (66,7%)

Intranasal Results:
inert   cellulose powder in prevention 1.8and
  management of SAR in
Blocked B
within 6nasal
weekspassages 0.7   Powder).
children
oms of allergic rhinitis in scores in Group 1 (the Inert Cellulose
Efficacy of the Inert Cellulose Powder in children with seasonal s Is
Geppe NA, et al. Poster presentation at European Academy of
Itching in the nose 1.1Allergy
  and Clinical Immunology Meet, London 2010
Rhinorrhea
0.5   in the nose
Itching Sneezing

Sneezing
Sneezing
1.5  
0.5  
N = 110 (Itchingmeanin the nose 2
a
age 8.5 yr) Blocked nasal passages Rhinorrhea
0.8  
1.8  
children* Р <with
0,05

positive history
V isit 4

of SAR
y of the Inert Cellulose Powder in children with AR during the first two weeks (р<0,05)

HPMC grouppassages =
1.8  
• Blocked nasal 0.7  
Inert Cellulose Montelukast Sodium
Powder Cromoglicate
Budesonide Before Inert Cellulose Montelukast Sodium
Issiue Powder Cromoglicate
Budesonide

Powder 30in children


Itching in the nosewith seasonal
0.5  
1.1   symptoms AR within 6 weeks compared with other variants of treatment
• Montelukast 5
Sneezing 1.5   Rhinorrhea Blocked nasal passages
mg = 30
Sneezing 0.5   2 weeks
after Issue
• SC 100 mg BD = 0.8  
Rhinorrhea 1.8  

20
• Budesonide 50
mcg TID/QID =
30with seasonal symptoms AR within 6 weeks compared with other variants of treatment.
r in children
Sneezing
Conclusion:
Rhinorrhea Blocked nasal passages

FU visits @ 2, 4,
Visit 1

wder
and
Cellulose 6 weeks
Montelukast Sodium
Cromoglicate
Budesonide Inert Cellulose Montelukast Sodium
Powder Cromoglicate
Budesonide
After 6
Inert Cellulose Montelukast Sodium Budesonide
Powder Cromoglicate
weeks
Pediatric population
Study of mucociliary clearance in children with allergic rhinitis, before and after a
6-week therapy with natural cellulose powder
Aivazis V, et al. Poster presented at World Allergy Congress, Munich, June 2005 Published: Nea Pediatrica Chronica 2005

Results
N = 100 (mean age 7.9 yr) children with
positive history of AR Mucocilary clearance
Before After
78/93 children (83.8%) had high total
IgE titres, specific IgE ABs, or positive 39 min 18.5 min
skin tests
51 children with prolonged clearance
Mucociliary clearance determined by Mucocilary clearance
non-invasive dye method before and
Before After
after therapy for 6 weeks
55.2 min 21.1 min

Conclusions:
• Significant decrease in mucociliary clearance is due to effect of
cellulose, as no other therapy was used
• Cellulose enhances nasal mucus which allows filtration of
allergens, allowing only clean air to reach the lungs
Nezact
Evidence from clinical trials
Paediatric Adult
Reviews 20 successful clinical
population population trials conducted on
Nezact
• Aivazis, et al (2005) • Josling, et al (2003) • Prof Patrick, et al
• Aberg, et al (2010) • Vlahtis, et al (2004) (2008) Showing statistically
Emberlin, et al (2004) • Popov et al (2017)
Geppe, et al (2009) significant symptom relief
• •
• Emberlin, et al (2006)
• Emberlin, et al (2007) and published in quality
• Zakharzhevskaya, et al journals
(2009)
• Ilina, et al (2011) Research carried out in
• Diethart, et al (2010) UK, China, Sweden,
• Penechko, et al (2011) Ukraine, Russia, Bulgaria
Angotoyeva, et al
and Greece

(2011)
• Aberg, et al (2014)
• Valerieva, et al (2015) Proven efficacy in children
• Popov, et al (2016) and adults against pollen
• Lanlan, et al (2015) and house dust mite
allergen

Total studies population


almost 1,000 people;
children, teenagers and
adults
Any guideline
recommendation
?
2016, VOL. 17, NO 5, 657-669

“Other relatively new treatments for PAR or PER


include H3-antihistamines, toll-like receptor (TLR)
agonists, cellulose powders and micro-emulsions,
novel biomolecular formulations and omalizumab.”
86
1. Nezact contains HPMC
2. HPMC forms a gel like barrier thereby
◦ Blocking the allergens
◦ Providing protection and re-enforcing the natural barrier
3. Nezact is given the GRAS status by the USFDA
4. Well designed randomized double blind control available with Nezact
5. Studies as:
◦ Monotherapy
◦ Add-on to conventional medication (both oral and nasal spray)
◦ All forms of allergic rhinitis
◦ Paediatric age group
6. Concept of muco-adhesion will lead to synergism when used with intra
nasal sprays
7. Recommended by BSACI guideline-2017
INTRODUCTION TO ALLERGIC RHINITIS

PATHOPHYSIOLOGY, DIAGNOSIS & MANAGEMENT

NEED FOR A NEW MOLECULE


nidu

NEZACT

TAKE HOME MESSAGE


1. AR is a common condition in India
2. AR is an Ig E mediated inflammatory disease
3. In AR there is a vicious cycle of nasal inflammation
and dysregulation of natural protective barrier
4. Allergen avoidance is the first step in the
management of AR
5. Nezact contains HPMC- an inert material which acts
as physical barrier, protecting and reinforcing the
natural barrier
6. Nezact can be used in all forms of allergic rhinitis
7. Nezact is given the ‘GRAS’ status by the USFDA
8. More than 1000 patients, 20 clinical trials and
guideline recommendation are available for Nezact
BLANK SLIDE

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