Dymista ® in 90 minutes *Carr et al. A novel intranasal therapy of azelastine with fluticasone for...

Dymista® in 90 minutes

*Carr et al. A novel intranasal therapy of azelastine with fluticasone for the treatment of allergic rhinitis. J Allergy Clin Immunol. 2012; 129(5): 1282-1289. Leung et al. MP29-02: A major advancement in the treatment of allergic rhinitis. J Allergy Clin Immunol. 2012; 129(5): 1216.

Agenda

• Introduction

• Unmet medical need in Allergic Rhinitis and the patient perspective

• Dymista®: the drug of choice for the treatment of Allergic Rhinitis

• Dymista® versus commercially available first line therapy

• Wrap-up and discussion

Unmet medical need with current Allergic Rhinitis therapy: SCUAD

• Up to 20% of Allergic Rhinitis patients receiving an optimal pharmacologic treatment (according to guidelines) still present with severe symptoms

• These patients are ascribed to Severe Chronic Upper Airway Disease (SCUAD)

Bousquet et al, 2009 & 2010

Before

Controlled

SCUAD

n=586

Med

ian

sco

re

Global Sleep Practical Eye Emotions

Unmet medical need with current allergic rhinitis (AR) therapy

• Patients use multiple therapies to achieve AR symptom control

− As many as 90% of patients in a recent survey - despite the fact that there is limited evidence to support this practice

− 60% of all AR patients are “very interested” in finding a new medication and 25% are “constantly” trying different medications to find one that “works”

There is a clear need for a new and more effective therapyThere is a clear need for a new and more effective therapy

Canonica et al, 2007; Schatz, 2007; Mullol et al, 2009; Demoly et al, 2002; Bousquet et al, 2012; Bousquet et al, 2008; Marple et al, 2007

Up to 90% of patients already take 2 or more rhinitis medications

Canonica Schatz BousquetDemolyMullol

% o

f P

atie

nts

Can Dymista® change the landscape of AR management?

• Fast relief: SABA• Sustained relief: LABA• Preventer: ICS• Unmet medical need

− Most patients were taking SABA, LABA and ICS

− Convenient treatment needed to simplify asthma management as per recommendations




• Fast relief: anti-histamines• Sustained & most effective relief:

intranasal corticosteroids• Unmet medical need

− Changing face of the disease− 20% SCUAD− 75% of patients on unproven combination

therapy− More effective therapies urgently needed





….to the same extent as that seen in asthma management

Asthma LandscapeAsthma Landscape

Many asthmatics now on LABA/ICS formulations

Dymista® a new paradigm for Allergic Rhinitis management

Rhinitis LandscapeRhinitis Landscape

SABA: short-acting beta-agonist; LABA: long-acting beta-agonist; SCUAD: severe chronic upper airway disease

Unmet medical need in Allergic Rhinitis and the patient perspective

The Allergy Epidemic

• The financial cost of allergy in Europe alone has been estimated at 100 billion euro/year

EU Summit Report, 2008

Allergies becoming more severeAnaphylaxis increased 7 foldAllergies becoming more severeAnaphylaxis increased 7 fold

Allergies arecontinuously rising,affecting 50% of allEuropeans by 2015

Allergies arecontinuously rising,affecting 50% of allEuropeans by 2015

The clinical picture of allergic rhinitis is changing

European Survey– 67.2% = moderate or severe

– 42.5% = persistent disease

SCUAD

- approx. 30% of AR patients

Shift from ‘mild’ to ‘moderate/severe’ Allergic RhinitisShift from ‘mild’ to ‘moderate/severe’ Allergic Rhinitis

Shift to mixed forms of Allergic RhinitisShift to mixed forms of Allergic Rhinitis

More patients are becoming poly-sensitizedMore patients are becoming poly-sensitized

Evolution of treatment-resistant phenotypes• Severe Chronic Upper Airway Disease

(SCUAD)

Evolution of treatment-resistant phenotypes• Severe Chronic Upper Airway Disease

(SCUAD)

Canonica et al, 2007; Settipane, 2001; Mosges & Klimek, 2007; Bousquet et al, 2009

Pie chart: data refers to non-infectious rhinitis; AR: Allergic Rhinitis

Allergic

Non-allergic

Mixed

In Sweden, the cost of rhinitis is €2.7 billion/yr in terms of lost productivity

In Sweden, the cost of rhinitis is €2.7 billion/yr in terms of lost productivity

Valovirta et al, 2008, Hellgren et al, 2010

The patient voice allergy survey

Allergic Rhinitis impacts negatively patients’ activities

High socioeconomic costs

Intermittent (n=1257)

Pat

ien

ts w

ith

mo

der

ate

to s

ever

e im

pac

t (%

)

Sport/exercise

Visiting friends

Holiday Indoor activities

Public transport

Work Sleep Going out

Outdoor activities

Persistent (n=2305)

Allergic Rhinitis impacts patients’ sleep & emotional well-being

• Up to 52% of AR patients do not feel rested after sleep

• Up to 49% wake up during the night

• Up to 32% have difficulty getting to sleep

• AR has a significant emotional impact in 77% of persistent AR and 66% of intermittent AR patients

Valovirta et al, 2008

AR: Allergic Rhinitis

The patient voice allergy surveyPersistent (n=2305)

Intermittent (n=1257)

Pat

ien

ts w

ith

mo

der

ate

to s

ever

e im

pac

t (%

)%

o

f P

atie

nts

Severe

Moderate

Mild

Absent

Not feeling rested on waking

Disturbed sleep

Difficulty going

to sleep

Tired Irritable Poor Conc.

Self Conscious

Allergic Rhinitis impacts school performance

• Comparing adolescents’ exam performance during ‘mock’ examinations (conducted in winter) with formal exam in summer

− Current symptomatic hay fever associated with 50% increase in risk of dropping exam grade between winter and summer

− For those taking hay fever medications risk increased by 40%

− And those taking sedating medications risk increased by 70%

Walker et al, 2007

What is actually achieved?What is actually achieved?

Allergic rhinitis is commonly associated with co-morbidities

• Individuals with active rhinitis symptoms are 1.5-4.5 times more likely to suffer from co-morbid conditions including:

– Asthma– Otitis media– Sinusitis– Eczema– Food and insect bite allergies– Migraine and Depression

Up to three quarters of asthmatics have allergic rhinitis and these patients are more likely to have uncontrolled asthma

Up to three quarters of asthmatics have allergic rhinitis and these patients are more likely to have uncontrolled asthma

More patients with rhinitis have uncontrolled asthma

Derebery et al, 2008; Vandenplas et al, 2008

%

of

pat

ien

ts w

ith

u

nco

ntr

oll

ed a

sth

ma

No rhinitis

Allergic rhinitis

Non-allergic rhinitis

Patients reporting severe rhinitis exhibit the worst asthma control – on a par with current smokers

Patients reporting severe rhinitis exhibit the worst asthma control – on a par with current smokers

Based on a survey of 4,429 patients prescribed ICS in 83 UK general practices

Multiple logistic regression: predicting poor control (ACQ score >1.25)

Clatworthy J, Price D et al. Prim Care Resp J 2009ICS: inhaled corticosteroid

Rhinitis predicts poor control of asthma

The majority of patients with Allergic Rhinitis felt irritable, tired and miserable in 2006 as well as in 2010

The majority of patients with Allergic Rhinitis felt irritable, tired and miserable in 2006 as well as in 2010

AIA, Allergies in America survey; AR, Allergic Rhinitis; NASAL, Nasal Allergy Survey Assessing Limitations.

Impact of current Allergic Rhinitis therapy on real life measures have not improved

Res

po

nd

ents

(%

)

Irritable Tired Embarrased Miserable

NASAL 2010(n=400)

AIA 2006(n=2500)

Depressed

What do allergic rhinitis patients want and how do they treat their symptoms?

• 1,000 Allergic Rhinitis patients completed the survey− 254 mild

− 746 moderate/severe patients (total nasal symptom score [TNSS]) ≥8/12, (incl. congestion score ≥2)

− Recruited through a patient panel

• The survey included questions on respondents’ − Treatment

− Episode duration

− Impact of symptoms on productivity

− Other questions

Results from a new health survey including 1,000 patients

Pitman et al, 2012

What do Allergic Rhinitis patients want?

• Discrete choice experiments are based on the premise that any good or service can be described by its characteristics (or attributes)

• Secondly, the extent to which an individual values a good or service can be described in terms of the levels of these characteristics

• The technique involves presenting individuals with choices of scenarios described in terms of attributes and associated levels

• Participants are asked to choose their preferred scenario

Introduction to the world of Discrete Choice Experiments

What do Allergic Rhinitis patients want?

• Patients were presented with 7 product characteristics:1. Maximum symptom relief (mild, moderate, complete)

2. Time to maximum relief (3, 7, 14 days)

3. Time to first dose benefit (0.5, 3, 8 hours)

4. Risk of side effects (2%, 5%, 10%)

5. Administration method (tablet, nasal spray, both)

6. Frequency of medication (once, twice, three times/day)

7. Monthly out-of-pocket cost (£15, £30, £45). Patients were asked to imagine that they paid the full cost of this prescription medication

• Patients were presented with 19 pairs of ‘potential Allergic Rhinitis products’ (based on the above characteristics) and asked to choose between them

We asked them using a Discrete Choice Experiment (DCE)

An Example Choice Set

Patients were presented with 19 of these and asked to pick ‘A’ or ‘B’

DCE Results: moderate to severe SAR patients

• Patients want more efficacious treatments which provide complete or substantial treatment relief

• Patients where willing to pay £43 to receive such a medication

CI: confidence interval; WTP: willingness to pay

DCE: discrete choice experiment; SAR: Seasonal Allergic Rhinitis

Treatment efficacy drives patient preference for rhinitis treatmentTreatment efficacy drives patient preference for rhinitis treatment

DCE Results: mild SAR patients

• Even patients with mild AR symptoms wanted more efficacious treatments

• Patients where willing to pay £28 to receive such a medication

Treatment efficacy drives patient preference for rhinitis treatmentTreatment efficacy drives patient preference for rhinitis treatment

CI: confidence interval; WTP: willingness to pay

DCE: discrete choice experiment; SAR: Seasonal Allergic Rhinitis

Implications of Discrete Choice Experiment Results

INS: intranasal steroid; OTC: over the counter

New results from a health utilisation surveyincluding 1,000 patients

• An average symptom SAR episode lasts 12.5 days for moderate/severe patients and 9.8 days for mild patients

• Patients with mild SAR have 6 episodes per year

• Patients with moderate/severe SAR have 8 episodes per year

• Work is negatively impacted by over 90% of patients


Symptom episodes are short but occur many times during the season with a negative impact

Impact on work productivity

% o

f P

atie

nts

Productivity impacted

10%

20%

30%

40%

50%

60%

70%

80%

90%

Unabl

e to

…

No im

pact

New results from a health utilisation surveyincluding 1,000 patients

• Two thirds of all patients incl. in the survey reported using ≥ 2 AR medications

− 70.5% of moderate to severe

− 56.1% of mild patients

• The need for faster and more effective treatment was the primary reason for co-medicating

− True for both moderate/severe and mild patients

Pitman et al, 2012; AR: Allergic Rhinitis

Most patients use multiple therapies to control their symptoms

Faster and more effective reduction of nasal and ocular symptoms are the treatment targets of drug development

Faster and more effective reduction of nasal and ocular symptoms are the treatment targets of drug development

% moderate/severe patients on 2 ≥ AR medications

Total Increased nasal

efficacy

Increased ocular

efficacy

Faster nasal

response

Faster ocular

response

Other

% o

f P

atie

nts

Conclusions

• The clinical picture of Allergic Rhinitis is changing to more severe and mixed forms

• Allergic rhinitis has a negative impact on virtually every aspect of patients’ lives

• Most patients use multiple therapies in an attempt to achieve faster and better symptom control

• Patients with Allergic Rhinitis want more efficacious treatments which provide complete or substantial treatment relief

Faster and more effective nasal and ocular symptom control are the future drug development targets

Faster and more effective nasal and ocular symptom control are the future drug development targets

Dymista®: the drug of choice for the treatment of Allergic Rhinitis

The ARIA guidelines

Bousquet et al, 2008; Brozek et al, 2010; Carr et al, 2012; Hampel et al, 2010ARIA: allergic rhinitis and its impact on asthma

MEDA’s Clinical Development Programme represents to date the largest body of evidence directly comparing first-line therapies for

Allergic Rhinitis

MEDA’s Clinical Development Programme represents to date the largest body of evidence directly comparing first-line therapies for

Allergic Rhinitis

Dymista®: A snapshot

• What is it?− Dymista® is a novel intranasal formulation of Azelastine hydrochloride and

Fluticasone propionate in one nasal spray (total daily dose: 548/200 µg)

• Where is it approved?

− Dymista® has been approved by the FDA in May 2012

− Dymista® has been approved by the EU in January 2013

− Licensing authority registration conditions differ from country to country

Dymista®: a novel intranasal formulation of intranasal Fluticasone propionate and Azelastine hydrochloride

• 4 phase III, multi-centre, randomised, double-blind, placebo-controlled, parallel group trials (SAR trials)

• One long-term open-label safety study (chronic rhinitis trial)

• In all, 4,617 patients

• Objectives: − To directly compare the efficacy and safety of Dymista® with Azelastine and

Fluticasone propionate nasal sprays in patients with moderate-to-severe SAR

− To assess the long-term safety of Dymista® in patients with chronic rhinitis

Overview of Clinical Development programme

Hampel et al, 2010; Carr et al, 2012; ; Price et al, 2012;

SAR: seasonal allergic rhinitis

Dymista® clinical programme summary

Hampel et al, 2010; Carr et al, 2012; Price et al, EAACI , 2012FP: fluticasone propionate; ITT: intent to treat

The largest body of evidence directly comparing the effectiveness of anti-rhinitis medications

Dymista® study design: Seasonal Allergic Rhinitis Studies

NS: nasal spray; TNSS: Total Nasal Symptom Score; TOSS: Total Ocular Symptom Score; bid: twice daily

Hampel et al, 2010; Carr et al, 2012

Dymista® NS

Fluticasone propionate NS

Azelastine NS

Placebo

Day 7Screening

Day 1Randomisation

Day 7Visit

Day 14Visit

Symptom qualification period

Daily TNSS/TOSS Daily Assessment(AM & PM)

Placebo run-inPlacebo run-in

1 spray/nostril bid

Dymista® trial patients

• ≥ 12 years old with a ≥ 2-year history of Seasonal Allergic Rhinitis (SAR)

• Positive skin prick test to relevant pollen

• Moderate-to-severe SAR− Defined by ARIA guidelines

− Defined by baseline rTNSS, nasal congestion scores and rTOSS

• At randomisation patients demonstrated:− Baseline rTNSS of 18-19 (max =24)

− Baseline rTOSS of 11-12 (max =18)

Patients had moderate to severe Seasonal Allergic Rhinitis

ARIA: Allergic Rhinitis and its impact on asthma; rTNSS: reflective total nasal symptom score; rTOSS: reflective Total Ocular Symptom Score;

Hampel et al, 2010; Hampel et al, 2010; Carr et al, J Allergy Clin

The majority of randomized patients with Allergic Rhinitis have moderate-to-severe disease

The majority of randomized patients with Allergic Rhinitis have moderate-to-severe disease

Endpoints

• Reflective total nasal symptom score [rTNSS] (AM + PM) − Maximum score = 24

• Reflective total ocular symptom score [rTOSS] (AM + PM)− Maximum score = 18

• Individual nasal and ocular symptoms− Nasal: congestion; itching; rhinorrhoea; sneezing

− Ocular: itching, redness, watering

• rTNSS by patient baseline severity

• Substantial treatment response (requested by EMA)− 50% reduction from baseline in rTNSS

− ≤ 1 point remaining for EACH nasal symptom (i.e. complete/almost complete symptom relief)

Hampel et al, 2010; Carr et al, J Allergy Clin

rTNSS baseline ranges were: MP4002: 18.19-18.61; MP4004: 18.22-18.59; MP4006: 19.37-19.51

MP4002: † p=0.034 vs Dymista®; ‡ p=0.001 vs Dymista®; * p<0.001 vs Dymista®; MP4004: † p=0.038 vs Dymista®;

‡ p=0.032 vs Dymista®; * p<0.001 vs Dymista®; MP4006: † p=0.029 vs Dymista®; ‡ p=0.001 vs Dymista®; * p<0.001 vs Dymista®

AZE: Azelastine; FP: Fluticasone propionate; rTNSS: reflective Total Nasal Symptom Score

Carr et al, J Allergy Clin

Consistent benefit of Dymista® across “ALL SEASONS”

Dymista® 5.61 5.54 5.53

FP 4.71 4.55 4.89

AZE 4.23 4.54 4.82

PLA 2.92 3.03 3.4

Spring Autumn Spring & Summer

LS

Mea

n C

han

ge

fro

m

Bas

elin

e in

rT

NS

S

MP4002 MP4004 MP4006

Significantly greater baseline rTNSS reduction

rTNSS: reflective Total Nasal Symptom Score; FP: Fluticasone propionate; AZE: Azelastine; PLA: placebo


MP4002 (n=831) MP4004 (n=776)

† p=0.034 vs Dymista®; ‡ p=0.002 vs Dymista ® † p=0.038 vs Dymista®; ‡ p=0.032 vs Dymista ®

AZEFP AZEFP

∆ P

lace

bo

LS

Mea

n

Ch

ang

e fr

om

B

asel

ine

rTN

SS

∆ P

lace

bo

LS

Mea

n

Ch

ang

e fr

om

B

asel

ine

rTN

SS

Significantly greater baseline rTNSS reduction

rTNSS: reflective Total Nasal Symptom Score; FP: Fluticasone propionate; AZE: Azelastine; PLA: placebo


MP4006 (n=1971) Meta-analysis (n=3398)

† p=0.029 vs Dymista®; ‡ p<0.016 vs Dymista ® † p=0.001 vs Dymista®; ‡ p<0.001 vs Dymista ®

AZEFP AZEFP

∆ P

lace

bo

LS

Mea

n

Ch

ang

e fr

om

B

asel

ine

rTN

SS

∆ P

lace

bo

LS

Mea

n

Ch

ang

e fr

om

B

asel

ine

rTN

SS

Better clinical benefit was observed from the first day of assessment and was sustained

* p <0.001 vs all active treatments; † p ≤ 0.015 vs Dymista®; ‡ p ≤ 0.050 vs Dymista®

Dymista® (n=848) ;AZE: Azelastine (n=847); FP: Fluticasone propionate (n= 846); Placebo (n= 857); rTNSS: reflective Total Nasal Symptom Score


FP

PLA

rTN

SS

(L

S M

ean

Ch

ang

e fr

om

Bas

elin

e)

Day

AZE

Start

* p≤0.0008 vs Dymista®; † p≤0.0047 vs Dymista®; ‡ p=0.0125 vs Dymista®

Dymista® (n=848) ;AZE: Azelastine (n=847); FP: Fluticasone propionate (n= 846); Placebo (n= 857)


Dymista® targets all the different nasal symptoms of Allergic Rhinitis

AZE

∆ P

lace

bo

LS

Mea

n C

han

ge

fro

m

Bas

elin

e: i

nd

ivid

ual

sym

pto

m s

core

FP

Congestion Rhinorrhea SneezingItch

† p=0.0073 vs Dymista®; ‡ p=0.0379 vs Dymista®

Dymista® (n=848) ;AZE: Azelastine (n=847); FP: Fluticasone propionate (n= 846); Placebo (n= 857)


Dymista® targets all the different ocular symptoms of Allergic Rhinitis

AZE

FP

∆ P

lace

bo

LS

Mea

n C

han

ge

fro

m

Bas

elin

e: i

nd

ivid

ual

sym

pto

m s

core

Itch Watery Redness

Effective even in more severe patients

* p ≤0.0001 vs all active treatments; † p <0.04 vs Dymista®; ‡ p< 0.01 vs Dymista®

rTNSS: reflective Total Nasal Symptom Score; RQLQ: Rhinitis Quality of Life Questionnaire; FP: Fluticasone propionate; AZE: Azelastine; PLA: placebo


AZE

FP

PLA

rTN

SS

(L

S m

ean

ch

ang

e fr

om

bas

elin

e)

rTNSS ≤ 18.9 rTNSS > 18.9 RQLQ ≤ 3.9 RQLQ > 3.9

Substantial treatment response with Dymista®

AZE: Azelastine; FP: Fluticasone propionate ; PLA: placebo

Carr et al, 2012. Responder rate = % of patients who achieved the specified response

Day

rTNSS 50% responseR

esp

on

der

Rat

e (%

) AZE

FP

PLA

Start

Complete treatment response with Dymista®

AZE: Azelastine; FP: Fluticasone propionate ; PLA: placebo

Carr et al, 2012. Responder rate = % of patients who achieved the specified response

rTNSS (≤1 point for all symptom scores)

Day

Res

po

nd

er R

ate

(%)

AZE

FP

PLA

Start

These results have been published in JACI

• ‘Prior to MP29-02 [Dymista®], no clinical development program has demonstrated additional benefit over two currently recommended first-line AR therapies in moderate-to-severe patients’

• ‘Patients with moderate-to-severe SAR achieved better control and were controlled earlier with MP29-02 [Dymista®] than with recommended medications according to guidelines’

• ‘The results are consistent among different parameters, including ocular symptoms, and across various allergy seasons’

• ‘’MP29-02 [Dymista®]provided benefits for all patients, providing significantly greater symptom relief than Fluticasone propionate or Azelastine monotherapy regardless of disease severity’

Take home messages

Carr et al, 2012JACI: Journal of Allergy & Clinical Immunology; AR: Allergic Rhinitis; SAR: Seasonal Allergic Rhinitis

Editors’ choice J Allergy Clin Immunol

• ‘MP29-02 [Dymista®]: A major advancement in the treatment of Allergic Rhinitis’• ‘MP29-02 [Dymista®]: can be considered the drug of choice for the treatment of

Allergic Rhinitis’


Dymista® versus commercially first line therapy

The treatment effect of Dymista® becomes even more striking when comparing it to commercially-available FP – the Meda Fluticasone propionate

preparation masks the ‘real world’ effects of Dymista®

The treatment effect of Dymista® becomes even more striking when comparing it to commercially-available FP – the Meda Fluticasone propionate

preparation masks the ‘real world’ effects of Dymista®

Dymista® versus commercially available first line therapy

The importance of Study MP4001

Hampel et al, 2010; Carr et al, 2012; Price et al, EAACI , 2012FP: fluticasone propionate; ITT: intent to treat

Hampel et al, 2010; Carr et al, 2012AZE: azelastine; FP: fluticasone propionatel; rTNSS: reflective total nasal symptom socre;

Data presented as LS mean change from baseline delta placebo with 95% CI

Dymista® is more effective in reducing nasal AR symptoms compared to commercially available first-line therapy

Not commercial available first line therapy

Commercially available first line therapy

FP AZE

LS

Mea

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ine

in r

TN

SS

(Del

ta p

lace

bo)

† p<0.0001 vs Dymista®; ‡ p=0.0031 vs Dymista®

Patients treated with Dymista® experience significant relief from all their nasal symptoms

Better than intranasal Fluticasone or Azelastine

Dymista® (n=153); FP: Fluticasone propionate (n=151); AZE: azelastine (n=152)

Hampel et al, 2010. Results expressed as LS mean change from baseline (delta placebo) with 95% CI

† p=0.0034 vs Dymista®; ‡ p=0.0001 vs Dymista® † p=0.0240 vs Dymista®; ‡ p=0.0033 vs Dymista®

Nasal Congestion Nasal Itch

LS

Mea

n C

han

ge

fro

m B

asel

ine

(Del

ta p

lace

bo)

AZEFP AZEFP

LS

Mea

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han

ge

fro

m B

asel

ine

(Del

ta p

lace

bo)

Patients treated with Dymista® experience significant relief from all their nasal symptoms

Dymista® (n=153) FP: Fluticasone propionate (n=151); AZE: azelastine (n=152) ; Hampel et al, 2010. Results expressed as LS mean change from baseline (delta placebo) with 95% CI

Better than intranasal Fluticasone and Azelastine

† p=0.0678 vs Dymista®; ‡ p<0.0001 vs Dymista® † p=0.0009 vs Dymista®; ‡ p<0.0001 vs Dymista®

Rhinorrhea Sneezing

AZEFP AZEFPL

S M

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e (D

elta

pla

cebo

)

LS

Mea

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(Del

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Dymista® (n=153); FP: Fluticasone propionate (n=151); AZE: azelastine (n=152); rTOSS: reflective Total Ocular Symptom Score; SAR: Seasonal Allergic Rhinitis; Hampel et al, 2010; Data presented as LS mean change from baseline delta placebo with 95% CI

Dymista® is also more effective than intranasal steroids in treating the symptoms of conjunctivitis

• Approx 90% of SAR patients also experience eye symptoms during the season• Patients treated with Dymista® experienced significantly better ocular symptom

relief than those treated with fluticasone with a relative difference of 58%

† p=0.0022 vs Dymista®; ‡ p=0.0706

AZEFP

LS

Mea

n C

han

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fro

m B

asel

ine

in r

TO

SS

(D

elta

pla

cebo

)

Hampel et al, 20120Dymista® (n=153); FP: Fluticasone propionate (n=151); AZE: azelastine (n=152); Data presented as LS mean change from baseline delta placebo with 95% CI


Patients treated with Dymista® experience significant relief from all their ocular symptoms

† p=0.0001 vs Dymista®

‡ p=0.0127 vs Dymista®





Watering Itching Redness

AZEFP AZEFP AZEFP

LS

Mea

n C

han

ge

fro

m B

asel

ine

(Del

ta p

lace

bo)

† p=0.0013 vs Dymista®; ‡ p=0.0004 vs Dymista®;

Dymista® (n=153); FP: Fluticasone propionate (n=151); AZE: azelastine (n=152); Data on file

rT7SS: Total of 7 symptom scores (All nasal pluis all ocular symptoms); Data on file; Results expressed as LS mean change from baseline (delta placebo) with 95% CI


Dymista® most effectively treats the entire rhinitis symptom complex (both nasal & ocular symptoms)

AZEFP

rT7S

S L

S M

ean

Ch

ang

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Bas

elin

e(D

elta

pla

cebo

)

AR: allergic rhinitis; AZE: Azelastine; FP: Fluticasone propionate; rTNSS: reflective Total Nasal Symptom ScoreData on file; Results expressed as LS mean change from baseline (delta placebo) with 95% CI

Most AR patients have moderate-to-severe disease

Dymista®: the most effective option regardless of severity

Most severe patients Moderate/ severe patients

LS

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SS

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AZEFP AZEFP


Dymista® (n=77); FP (n=64); AZE (n=68)



Dymista® is also more effective for those patients with moderate/severe ocular symptoms

rTOSS: reflective total ocular symptom score; ITT: intent to treat; AZE: Azelastine; FP: Fluticasone propionate; BL: baseline.

Data on file; Results expressed as LS mean change from baseline (delta placebo) with 95% CI

More severe patients

BI TOSS ≥ 8

ITT





LS

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AZEFP AZEFP

Dymista®: superior in providing faster and substantial symptom relief (≥ 50% reduction in nasal symptoms)

• More Dymista® patients achieve substantial symptom relief (1 in every 2 patients)

• And achieve this level of control up to 6 days faster than either FP or AZE

• Relevance:

A substantial response with up to 6 day’s time advantage over first-line therapy is relevant since an AR episode lasts 12.5 days on average

Substantial nasal symptom reduction is achieved by more Dymista® patients and up to 6 days earlier than existing first-line therapy

Substantial nasal symptom reduction is achieved by more Dymista® patients and up to 6 days earlier than existing first-line therapy

Bachert et al. EAACI 2011, AZE: Azelastine; FP: Fluticasone propionate; PLA: placebo; AR: allergic rhinitisResponder rate = % of patients with a 50% or more reduction in Total Nasal Symptom Score

Res

po

nd

ers

rate

(%

)

PLA

Day

6 days

AZEFP

Dymista®: More patients will be symptom-free than first-line therapy

• 1 out of 6 Dymista®

patients achieve complete or near-to-complete symptom relief

• Relevance:

Complete symptom relief is what patients want

80 million allergic rhinitis sufferers around the world could become symptom-free with Dymista®

80 million allergic rhinitis sufferers around the world could become symptom-free with Dymista®

AZE: Azelastine; FP: Fluticasone propionate; PLA: placebo

Data on file; Responder Rate = % of patients with a score of ≤ 1 for every nasal symptom

AZEFP

PLA

Res

po

nd

ers

rate

(%

)

Day

Dymista® is the drug that patients want

• Patients want more effective therapy and are willing to pay £43 to receive such medication (DCE results)

• Two thirds of all patients incl. in the survey reported using ≥ 2 AR medications

− Faster and more effective reduction of nasal and ocular symptoms was the primary reason for co-medication

Results of the health survey

Dymista® represents the drug which patients wantDymista® represents the drug which patients want

AR: Allergic Rhinitis; DCE: discrete choice experimentPitman et al, 2012

% moderate/severe patients on ≥ 2 AR medications

Total Increased nasal

efficacy

Increased ocular

efficacy

Faster nasal

response

Faster ocular

response

Other

% o

f P

atie

nts

MP4001 Conclusions

• The efficacy of Dymista® is more apparent compared to commercially-available first line therapy (than not commercially available comparators used in studies MP4002, MP4004 and MP4006 [i.e. the JACI publication])

• Dymista® is more effective than commercially first-line therapies in combating overall nasal symptoms (rTNSS), overall ocular symptoms (rTOSS) as well as each of the individual symptoms

• Dymista® provides benefits for all patients, providing significantly greater symptom relief vs FP or AZE regardless of disease severity

• More Dymista® patients achieved substantial nasal relief and achieved it earlier.

• 250 million patients will experience substantial symptom relief while 80 million patients will have no symptoms and feel themselves “cured”

Dymista® versus marketed comparators

AR: Allergic Rhinitis; rTNSS: reflective Total Nasal Symptom Score; rTOSS: reflective total ocular symptom score; FP: Fluticasone propionate; AZE: Azelastine

Wrap up and Discussion

Can Dymista® change the landscape of AR management?















….to the same extent as that seen in asthma management

Asthma LandscapeAsthma Landscape

Many asthmatics now on LABA/ICS formulations

Dymista® a new paradigm for Allergic Rhinitis management

Rhinitis LandscapeRhinitis Landscape

SABA: short-acting beta-agonist; LABA: long-acting beta-agonist; SCUAD: severe chronic upper airway disease

Dymista ® in 90 minutes *Carr et al. A novel intranasal therapy of azelastine with fluticasone for...

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