dymista ® in 90 minutes *carr et al. a novel intranasal therapy of azelastine with fluticasone for...
TRANSCRIPT
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: 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
• 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
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)
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
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
AR: Allergic Rhinitis
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
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
Carr et al, J Allergy Clin
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
Carr et al, J Allergy Clin
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
Carr et al, J Allergy Clin
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)
Carr et al, J Allergy Clin
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)
Carr et al, J Allergy Clin
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
Carr et al, J Allergy Clin
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’
AR: Allergic Rhinitis
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
n C
han
ge
fro
m B
asel
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
n C
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
ean
Ch
ang
e fr
om
Bas
elin
e (D
elta
pla
cebo
)
LS
Mea
n C
han
ge
fro
m B
asel
ine
(Del
ta p
lace
bo)
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
ge
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
Better than intranasal Fluticasone or Azelastine
Patients treated with Dymista® experience significant relief from all their ocular symptoms
† p=0.0001 vs Dymista®
‡ p=0.0127 vs Dymista®
† p=0.0218 vs Dymista®
‡ p=0.2923 vs Dymista®
† p=0.0044 vs Dymista®
‡ p=0.0372 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
Better than intranasal Fluticasone or Azelastine
Dymista® most effectively treats the entire rhinitis symptom complex (both nasal & ocular symptoms)
AZEFP
rT7S
S L
S M
ean
Ch
ang
e fr
om
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
Mea
n C
han
ge
fro
m B
asel
ine
In r
TN
SS
(Del
ta p
lace
bo)
AZEFP AZEFP
† p=0.0436 vs Dymista®; ‡ p=0.0035 vs Dymista®
Dymista® (n=77); FP (n=64); AZE (n=68)
† p=0.0188 vs Dymista®; ‡ p=0.0002 vs Dymista®
Dymista® (n=76); FP (n=87); AZE (n=84)
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
† p=0.0022 vs Dymista®; ‡ p=0.0706 vs Dymista®
Dymista® (n=153); FP (n=151); AZE (n=152)
† p=0.0012 vs Dymista®; ‡ p=0.0456 vs Dymista®
Dymista® (n=128); FP (n=125); AZE (n=118)
LS
Mea
n C
han
ge
fro
m B
asel
ine
In r
TO
SS
(Del
ta p
lace
bo)
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
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: 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
• 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