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)
Before
Controlled
Median score
SCUAD
n=586
Global
Sleep
Practical
Eye
Bousquet et al, 2009 & 2010
Emotions
Unmet medical need with current allergic rhinitis
(AR) therapy
• Patients use multiple therapies to
achieve AR symptom control
Up to 90% of patients already take 2 or
more rhinitis medications
− 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”
% of Patients
− As many as 90% of patients in a
recent survey - despite the fact that
there is limited evidence to support
this practice
Canonica
Schatz
Mullol
Demoly
There 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
Bousquet
Can Dymista® change the landscape of AR
management?
….to the same extent as that seen in asthma management
Asthma Landscape
•
•
•
•
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
Many asthmatics now on
LABA/ICS formulations
Rhinitis Landscape
•
•
•
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
Dymista® a new paradigm for
Allergic Rhinitis management
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
Allergies becoming more severe
Anaphylaxis increased 7 fold
Allergies are
continuously rising,
affecting 50% of all
Europeans by 2015
EU Summit Report, 2008
The clinical picture of allergic rhinitis is changing
Shift from ‘mild’ to ‘moderate/severe’
Allergic Rhinitis
European Survey
– 67.2% = moderate or severe
– 42.5% = persistent disease
Shift to mixed forms of Allergic Rhinitis
Allergic
More patients are becoming polysensitized
Non-allergic
Mixed
Evolution of treatment-resistant
phenotypes
SCUAD
• Severe Chronic Upper Airway Disease
(SCUAD)
- approx. 30% of AR patients
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 Rhinitis impacts negatively patients’
activities
The patient voice allergy survey
High socioeconomic costs
Persistent (n=2305)
Patients with moderate
to severe impact (%)
Intermittent (n=1257)
Outdoor
activities
Work
Sleep
Going
out
Sport/
exercise
Visiting
friends
Holiday
Indoor
Public
activities transport
In Sweden, the cost of rhinitis is €2.7 billion/yr in terms of
lost productivity
Valovirta et al, 2008, Hellgren et al, 2010
Allergic Rhinitis impacts patients’ sleep & emotional
well-being
The patient voice allergy survey
Patients with moderate
to severe impact (%)
Persistent
(n=2305)
• 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
Intermittent
(n=1257)
Not feeling
rested on
waking
• AR has a significant emotional
impact in 77% of persistent AR
and 66% of intermittent AR
patients
Disturbed
sleep
Difficulty
going
to sleep
Severe
% of Patients
Moderate
Mild
Absent
Tired
Valovirta et al, 2008
AR: Allergic Rhinitis
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%
What is actually achieved?
Walker et al, 2007
Allergic rhinitis is commonly associated with
co-morbidities
More patients with rhinitis have
uncontrolled asthma
–
–
–
–
–
–
Asthma
Otitis media
Sinusitis
Eczema
Food and insect bite allergies
Migraine and Depression
% of patients with
uncontrolled asthma
• Individuals with active rhinitis
symptoms are 1.5-4.5 times more
likely to suffer from co-morbid
conditions including:
No
rhinitis
Allergic
rhinitis
Non-allergic
rhinitis
Up to three quarters of asthmatics have allergic rhinitis and these
patients are more likely to have uncontrolled asthma
Derebery et al, 2008; Vandenplas et al, 2008
Rhinitis predicts poor control of asthma
Multiple logistic regression: predicting poor control
(ACQ score >1.25)
Variable
OR
95% CI
p
Compared with no
rhinitis:
reporting
severe
Patients
rhinitis exhibit the worst
Significant rhinitis
4.62current
3.71–5.77
asthma control
– on a par with
smokers<0.001
Rhinitis
Mild rhinitis
2.09
1.72–2.54
<0.001
Current smoker
4.33
3.58–5.23
<0.001
Ex smoker
1.59
1.36–1.87
<0.001
1.35
1.18–1.55
0.001
Compared with never
smoking:
Smoking
Adherence
Compared to high
adherers:
Low adherers
Based on a survey of 4,429 patients prescribed ICS in 83 UK general practices
Clatworthy J, Price D et al. Prim Care Resp J 2009
ICS: inhaled corticosteroid
Impact of current Allergic Rhinitis therapy
on real life measures have not improved
NASAL 2010
(n=400)
Respondents (%)
AIA 2006
(n=2500)
Depressed
Irritable
Tired
Embarrased
Miserable
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.
What do allergic rhinitis patients want and how do
they treat their symptoms?
Results from a new health survey including 1,000 patients
• 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
Pitman et al, 2012
What do Allergic Rhinitis patients want?
Introduction to the world of Discrete Choice Experiments
• 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
What do Allergic Rhinitis patients want?
We asked them using a Discrete Choice Experiment (DCE)
• 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
An Example Choice Set
Patients were presented with 19 of these and asked
to pick ‘A’ or ‘B’
LEVELS
Attribute
Treatment A
Treatment B
Maximum treatment symptom relief
Complete relief
Mild improvement
Time to achieve maximum treatment
symptom relief
7 days
14 days
Time to feel a benefit after first dose
3 hours
8 hours
10 in 100
2 in 100
Tablet
Nasal spray
Twice a day
Three times a day
£15 per month
£30 per month
Side effects
Administration method
Frequency of medication
Cost per month
Which treatment do you prefer?
A.
B.
DCE Results: moderate to severe SAR patients
Attribute
Odds Ratio
P Value
WTP
6.63
<0.01
£43.81
2.31
<0.01
£19.37
0.97
<0.01
-£0.62
0.96
<0.01
-£0.98
Side effects: per 1%
0.98
<0.01
-£0.40
Administration: tablets
vs. nasal spray
1.08
0.04
£1.80
Administration: tablets &
nasal spray vs. nasal spray
1.07
<0.01
£1.64
Frequency of
medication: times /day
0.87
<0.01
-£3.18
Cost: £1 / month increase
0.96
<0.01
Treatment relief: complete
vs. mild
Treatment relief:
moderate vs. mild
Time to maximum relief:
per day
Time to first dose
benefit: per hour
• Patients want
more
efficacious
treatments
which provide
complete or
substantial
treatment relief
• Patients where
willing to pay £43
to receive such a
medication
Treatment efficacy drives patient preference for rhinitis treatment
CI: confidence interval; WTP: willingness to pay
DCE: discrete choice experiment; SAR: Seasonal Allergic Rhinitis
DCE Results: mild SAR patients
Attribute
Odds Ratio
P Value
WTP
3.97
<0.001
£28.46
1.79
<0.001
£12.00
0.97
<0.001
-£0.60
0.97
<0.001
-£0.69
Side effects: per 1%
0.97
<0.001
£-0.55
Administration: tablets
vs. nasal spray
1.10
0.18
£1.91
Administration: tablets &
nasal spray vs. nasal spray
0.99
0.97
-£0.03
Frequency of
medication: times /day
0.87
<0.001
-£2.96
Cost: £1 / month increase
0.95
<0.001
Treatment relief: complete
vs. mild
Treatment relief:
moderate vs. mild
Time to maximum relief:
per day
Time to first dose
benefit: per hour
•
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 treatment
CI: confidence interval; WTP: willingness to pay
DCE: discrete choice experiment; SAR: Seasonal Allergic Rhinitis
Implications of Discrete Choice Experiment Results
Severity
Moderate to severe
Patients Want…
Complete or substantial
treatment relief
Implication(s)
• Current therapy is insufficient
• Patients are staying on oral
antihistamines too long
Mild
Complete or substantial
treatment relief
• Patients are resistant to taking INS
• Disease severity is under-estimated
• Patients are not visiting GP but selfmedicating with OTC treatments
INS: intranasal steroid; OTC: over the counter
New results from a health utilisation survey
including 1,000 patients
Symptom episodes are short but occur many times during the
season with a negative impact
Impact on work productivity
% of Patients
Productivity impacted
AR: Allergic Rhinitis
• 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
New results from a health utilisation survey
including 1,000 patients
Most patients use multiple therapies to control their symptoms
% moderate/severe patients on 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
% of Patients
• Two thirds of all patients incl. in the
survey reported using ≥ 2 AR
medications
Total
Increased
nasal
efficacy
Increased
ocular
efficacy
Faster
nasal
response
Faster
ocular
response
Faster and more effective reduction of nasal and ocular symptoms
are the treatment targets of drug development
Pitman et al, 2012; AR: Allergic Rhinitis
Other
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
Dymista®: the drug of choice for the treatment of
Allergic Rhinitis
The ARIA guidelines
• Intranasal corticosteroids are considered the most
effective treatment for Allergic Rhinitis
• There is a need for high-quality, direct head-to-head
comparison studies to further substantiate current
treatment recommendations (European Medicines
Agency)
MEDA’s Clinical Development Programme represents to date the largest
body of evidence directly comparing first-line therapies for
Allergic Rhinitis
Bousquet et al, 2008; Brozek et al, 2010; Carr et al, 2012; Hampel et al, 2010
ARIA: allergic rhinitis and its impact on asthma
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
Overview of Clinical Development programme
• 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
Hampel et al, 2010; Carr et al, 2012; ; Price et al, 2012;
SAR: seasonal allergic rhinitis
Dymista® clinical programme summary
The largest body of evidence directly comparing the effectiveness
of anti-rhinitis medications
Study number
Season
N (ITT)
MP-4001
2007/2008 Texas
Cedar
607
MP-4002
2008 spring
MP-4004
2008 fall
MP-4006
2009 spring and
summer
MP-4000
Chronic rhinitis – 1 yr
study in India
831
776
1791
612
Hampel et al, 2010; Carr et al, 2012; Price et al, EAACI , 2012
FP: fluticasone propionate; ITT: intent to treat
Comparators
Marketed
Comparators
Astelin® and generic
Fluticasone
Regulatory studies
Azelastine and
Fluticasone
formulated in
Dymista® vehicle and
applied in same
device
Marketed FP
(Safety Study)
Dymista® study design:
Seasonal Allergic Rhinitis Studies
1 spray/nostril bid
Dymista® NS
Fluticasone propionate NS
Placebo run-in
Azelastine NS
Placebo
Day 7
Screening
Day 1
Randomisation
Symptom qualification
period
Day 7
Visit
Daily TNSS/TOSS Daily Assessment
(AM & PM)
NS: nasal spray; TNSS: Total Nasal Symptom Score; TOSS: Total Ocular Symptom Score; bid: twice daily
Hampel et al, 2010; Carr et al, 2012
Day 14
Visit
Dymista® trial patients
Patients had moderate to severe Seasonal Allergic Rhinitis
• ≥ 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)
The majority of randomized patients with Allergic Rhinitis have
moderate-to-severe disease
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
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
Consistent benefit of Dymista® across
“ALL SEASONS”
Spring
Autumn
LS Mean Change from
Baseline in rTNSS
Spring & Summer
MP4002
Dymista®
MP4004
MP4006
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
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
Significantly greater baseline rTNSS reduction
∆ Placebo LS Mean
Change from
Baseline rTNSS
MP4004 (n=776)
∆ Placebo LS Mean
Change from
Baseline rTNSS
MP4002 (n=831)
FP
AZE
† p=0.034 vs Dymista®; ‡ p=0.002 vs Dymista ®
FP
AZE
† p=0.038 vs Dymista®; ‡ p=0.032 vs Dymista ®
rTNSS: reflective Total Nasal Symptom Score; FP: Fluticasone propionate; AZE: Azelastine; PLA: placebo
Carr et al, J Allergy Clin
Significantly greater baseline rTNSS reduction
Meta-analysis (n=3398)
∆ Placebo LS Mean
Change from
Baseline rTNSS
∆ Placebo LS Mean
Change from
Baseline rTNSS
MP4006 (n=1971)
FP
AZE
† p=0.029 vs Dymista®; ‡ p<0.016 vs Dymista ®
FP
AZE
† p=0.001 vs Dymista®; ‡ p<0.001 vs Dymista ®
rTNSS: reflective Total Nasal Symptom Score; FP: Fluticasone propionate; AZE: Azelastine; PLA: placebo
Carr et al, J Allergy Clin
Better clinical benefit was observed from the first
day of assessment and was sustained
rTNSS (LS Mean Change from Baseline)
FP
AZE
PLA
Start
Day
* 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
∆ Placebo LS Mean Change from
Baseline: individual symptom score
Dymista® targets all the different nasal symptoms of
Allergic Rhinitis
FP
AZE
Itch
Congestion
Rhinorrhea
Sneezing
* 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
∆ Placebo LS Mean Change from
Baseline: individual symptom score
Dymista® targets all the different ocular symptoms of
Allergic Rhinitis
FP
AZE
Itch
Dymista®
Watery
Redness
† p=0.0073 vs Dymista®; ‡ p=0.0379 vs Dymista®
(n=848) ;AZE: Azelastine (n=847); FP: Fluticasone propionate (n= 846); Placebo (n= 857)
Carr et al, J Allergy Clin
Effective even in more severe patients
rTNSS (LS mean change from baseline)
FP
AZE
PLA
rTNSS ≤ 18.9
rTNSS > 18.9
RQLQ ≤ 3.9
RQLQ > 3.9
* 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
Substantial treatment response with Dymista®
rTNSS 50% response
Responder Rate (%)
FP
AZE
PLA
Start
Day
AZE: Azelastine; FP: Fluticasone propionate ; PLA: placebo
Carr et al, 2012. Responder rate = % of patients who achieved the specified response
Complete treatment response with Dymista®
rTNSS (≤1 point for all symptom scores)
Responder Rate (%)
FP
AZE
PLA
Start
Day
AZE: Azelastine; FP: Fluticasone propionate ; PLA: placebo
Carr et al, 2012. Responder rate = % of patients who achieved the specified response
These results have been published in JACI
Take home messages
• ‘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’
Carr et al, 2012
JACI: 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
Dymista® versus commercially first line therapy
Dymista® versus commercially available 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 importance of Study MP4001
Study number
MP-4001
MP-4002
Season
2007/2008 Texas
Cedar
2008 spring
MP-4004
2008 fall
MP-4006
2009 spring and
summer
MP-4000
Chronic rhinitis – 1 yr
study in India
N (ITT)
607
831
776
1791
612
Hampel et al, 2010; Carr et al, 2012; Price et al, EAACI , 2012
FP: fluticasone propionate; ITT: intent to treat
Comparators
Marketed
Comparators
Astelin® and generic
Fluticasone
Regulatory studies
Azelastine and
Fluticasone
formulated in
Dymista® vehicle and
applied in same
device
Marketed FP
(Safety Study)
Dymista® is more effective in reducing nasal AR
symptoms compared to commercially available first-line
therapy
LS Mean Change
from Baseline in rTNSS
(Delta placebo)
Commercially available
first line therapy
Not commercial available
first line therapy
FP
AZE
† p<0.0001 vs Dymista®; ‡ p=0.0031 vs Dymista®
Hampel et al, 2010; Carr et al, 2012
AZE: azelastine; FP: fluticasone propionatel; rTNSS: reflective total nasal symptom socre;
Data presented as LS mean change from baseline delta placebo with 95% CI
Patients treated with Dymista® experience significant
relief from all their nasal symptoms
Better than intranasal Fluticasone or Azelastine
LS Mean Change
from Baseline
(Delta placebo)
Nasal Itch
LS Mean Change
from Baseline
(Delta placebo)
Nasal Congestion
FP
AZE
† p=0.0034 vs Dymista®; ‡ p=0.0001 vs Dymista®
FP
AZE
† p=0.0240 vs Dymista®; ‡ p=0.0033 vs Dymista®
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
Patients treated with Dymista® experience significant
relief from all their nasal symptoms
Better than intranasal Fluticasone and Azelastine
Sneezing
LS Mean Change
from Baseline
(Delta placebo)
LS Mean Change
from Baseline
(Delta placebo)
Rhinorrhea
FP
AZE
† p=0.0678 vs Dymista®; ‡ p<0.0001 vs Dymista®
FP
AZE
† p=0.0009 vs Dymista®; ‡ p<0.0001 vs Dymista®
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
Dymista® is also more effective than intranasal
steroids in treating the symptoms of conjunctivitis
LS Mean Change
from Baseline in rTOSS
(Delta placebo)
• 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%
FP
AZE
† p=0.0022 vs Dymista®; ‡ p=0.0706
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
Patients treated with Dymista® experience significant
relief from all their ocular symptoms
Better than intranasal Fluticasone or Azelastine
Watering
Redness
LS Mean Change
from Baseline
(Delta placebo)
Itching
FP
AZE
† p=0.0001 vs Dymista®
‡ p=0.0127 vs Dymista®
FP
AZE
† p=0.0218 vs Dymista®
‡ p=0.2923 vs Dymista®
Hampel et al, 20120
Dymista® (n=153); FP: Fluticasone propionate (n=151); AZE: azelastine (n=152)
; Data presented as LS mean change from baseline delta placebo with 95% CI
FP
AZE
† p=0.0044 vs Dymista®
‡ p=0.0372 vs Dymista®
Dymista® most effectively treats the entire rhinitis
symptom complex (both nasal & ocular symptoms)
rT7SS LS Mean Change
from Baseline
(Delta placebo)
Better than intranasal Fluticasone or Azelastine
FP
AZE
† 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®: the most effective option regardless of
severity
Most AR patients have moderate-to-severe disease
Moderate/ severe patients
LS Mean Change
from Baseline In rTNSS
(Delta placebo)
Most severe patients
FP
AZE
† p=0.0436 vs Dymista®; ‡ p=0.0035 vs Dymista®
Dymista® (n=77); FP (n=64); AZE (n=68)
FP
AZE
† p=0.0188 vs Dymista®; ‡ p=0.0002 vs Dymista®
Dymista® (n=76); FP (n=87); AZE (n=84)
AR: allergic rhinitis; AZE: Azelastine; FP: Fluticasone propionate; rTNSS: reflective Total Nasal Symptom Score
Data on file; Results expressed as LS mean change from baseline (delta placebo) with 95% CI
Dymista® is also more effective for those patients
with moderate/severe ocular symptoms
More severe patients
ITT
LS Mean Change
from Baseline In rTOSS
(Delta placebo)
BI TOSS ≥ 8
FP
AZE
† p=0.0022 vs Dymista®; ‡ p=0.0706 vs Dymista®
Dymista® (n=153); FP (n=151); AZE (n=152)
FP
AZE
† p=0.0012 vs Dymista®; ‡ p=0.0456 vs Dymista®
Dymista® (n=128); FP (n=125); AZE (n=118)
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
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)
Responders rate (%)
FP
AZE
PLA
6 days
Day
• 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
Bachert et al. EAACI 2011, AZE: Azelastine; FP: Fluticasone propionate; PLA: placebo; AR: allergic rhinitis
Responder rate = % of patients with a 50% or more reduction in Total Nasal Symptom Score
Dymista®: More patients will be symptom-free than
first-line therapy
Responders rate (%)
• 1 out of 6 Dymista®
patients achieve
complete or near-tocomplete symptom relief
FP
AZE
PLA
• Relevance:
Complete symptom
relief is what patients
want
Day
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
Dymista® is the drug that patients want
Results of the health survey
• Patients want more effective
therapy and are willing to pay
£43 to receive such medication
(DCE results)
− Faster and more effective
reduction of nasal and ocular
symptoms was the primary
reason for co-medication
% of Patients
• Two thirds of all patients incl. in
the survey reported using ≥ 2 AR
medications
% moderate/severe patients
on ≥ 2 AR medications
Total
Increased
nasal
efficacy
Increased
ocular
efficacy
Dymista® represents the drug which patients want
AR: Allergic Rhinitis; DCE: discrete choice experiment
Pitman et al, 2012
Faster
nasal
response
Faster
ocular
response
Other
MP4001 Conclusions
Dymista® versus marketed comparators
• The efficacy of Dymista® is more apparent compared to commerciallyavailable 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”
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 Landscape
•
•
•
•
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
Many asthmatics now on
LABA/ICS formulations
Rhinitis Landscape
•
•
•
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
Dymista® a new paradigm for
Allergic Rhinitis management
SABA: short-acting beta-agonist; LABA: long-acting beta-agonist; SCUAD: severe chronic upper airway disease