Study Design

DUPIXENT enrolled a total population of 2888 uncontrolled moderate-to-severe asthma patients across 3 pivotal trials

Trial 1(N=776) 24 Weeks Trial 2(N=1902) 52 Weeks Trial 3(N=210) 24 Weeks
Randomized DUPIXENT + SOC 200 mg Q2Wa (n=150)

Placebo + SOC (n=158)


DUPIXENT + SOC 300 mg Q2Wb (n=157)

Placebo + SOC (n=158)

DUPIXENT + SOC 200 mg Q2Wa (n=631)

Placebo + SOC (n=317)


DUPIXENT + SOC 300 mg Q2Wb (n=633)

Placebo + SOC (n=321)

DUPIXENT + SOC 200 mg Q2Wb (n=103)

Placebo + SOC (n=107)

Study
population

Adults (≥18 years) with moderate-to-severe asthma on a standard of care of medium- or high-dose ICS and a long-acting beta agonist

Adolescents (12-17 years) and adults (≥18 years) with moderate-to-severe asthma on a standard of care of medium- or high-dose ICS and a minimum of 1 and up to 2 additional controller medications; subjects with baseline blood eosinophil levels >1500 cells/μL (<1.3%) were excluded

Subjects (≥12 years) with asthma who required daily OCS in addition to regular use of standard of care of high-dose ICS plus an additional controller medication; subjects with baseline blood eosinophil levels >1500 cells/μL (<1.3%) were excluded

The total population of patients in Trials 1, 2, and 3 was unrestricted by minimum baseline blood eosinophil count

Study
population

The total population of patients in Trials 1, 2, and 3 was unrestricted by minimum baseline blood eosinophil count

The total population of patients in Trials 1, 2, and 3 was unrestricted by minimum baseline blood eosinophil count

The total population of patients in Trials 1, 2, and 3 was unrestricted by minimum baseline blood eosinophil count

Subjects continued background asthma therapy throughout the duration of the studies, except in Trial 3 in which OCS dose was reduced every 4 weeks during the OCS reduction phase (Weeks 4-20), as long as asthma control was maintained

Study
population

Subjects continued background asthma therapy throughout the duration of the studies, except in Trial 3 in which OCS dose was reduced every 4 weeks during the OCS reduction phase (Weeks 4-20), as long as asthma control was maintained

Subjects continued background asthma therapy throughout the duration of the studies, except in Trial 3 in which OCS dose was reduced every 4 weeks during the OCS reduction phase (Weeks 4-20), as long as asthma control was maintained

Subjects continued background asthma therapy throughout the duration of the studies, except in Trial 3 in which OCS dose was reduced every 4 weeks during the OCS reduction phase (Weeks 4-20), as long as asthma control was maintained

Primary
endpoint(s)

Mean change from baseline to Week 12 in FEV1 in patients with baseline eosinophils ≥300 cells/μL

Annualized rate of severe exacerbation events during the 52-week treatment period in the overall population


Mean change from baseline to Week 12 in FEV1 in the overall population

Percent reduction from baseline in OCS dose at
Weeks 20-24, while maintaining asthma control, in the overall population

Other
endpoints

Annualized rate of severe exacerbation events during the 24-week treatment periodc

Annualized rate of severe exacerbation events during the 52-week treatment period in patients with different baseline levels of eosinophils


Mean change from baseline to Week 52 in FEV1 in patients with different baseline levels of eosinophils


Responder rates in patient-reported AQLQ(S) and ACQ-5 scores

Annualized rate of severe exacerbation events during the 24-week treatment period


Mean change from baseline to Week 24 in FEV1

  • 1
  • 2
  • 3
  • aWith 400 mg loading dose.
  • bWith 600 mg loading dose.
  • cResults were evaluated in the overall population and subgroups based on baseline blood eosinophil count.
  •  
  • Q2W, once every 2 weeks.

TRIAL 1 (N=776) 24 WEEKS TRIAL 2 (N=1902) 52 WEEKS TRIAL 3 (N=210) 24 WEEKS
Mean age (SD), years 49 (13) 48 (15) 51 (13)
Mean duration of asthma (±SD), years 22 (15) 21 (15) 20 (14)
Mean exacerbations in previous year (±SD) 2.2 (2.1) 2.1 (2.2) 2.1 (2.2)
High-dose ICS use, % 50 52 89
Pre-dose FEV1 at baseline (±SD), L 1.84 (0.54) 1.78 (0.60) 1.58 (0.57)
Mean percent predicted FEV1 at baseline (±SD), % 61 (11) 58 (14) 52 (15)
Percent reversibility (±SD) 27 (15) 26 (22) 19 (23)
Atopic medical history, % overall
(atopic dermatitis, %)
(nasal polyposis, %)
(allergic rhinitis, %)
73
(8)
(11)
(62)
78
(10)
(13)
(69)
72
(8)
(21)
(56)
Mean FeNO (±SD), ppb 39 (35) 35 (33) 38 (31)
Mean total IgE (±SD), IU/mL 435 (754) 432 (747) 431 (776)
Mean baseline eosinophil count (±SD), cells/µL 350 (430) 360 (370) 350 (310)
  • 1
  • 2
  • 3
  • FeNO, fractional exhaled nitric oxide.

Severe Exacerbation Results

When added to maintenance therapy
DUPIXENT significantly reduced severe exacerbation rates

EOSINOPHIL COUNTS ≥300 CELLS/µL (primary analysis population, Trial 1): Significantly reduced rate of severe exacerbations when added to SOC (secondary endpoint)a

Severe exacerbations through Week 24
BASELINE BLOOD EOS ≥300 CELLS/µL

SOC=medium- or high-dose ICS and a long-acting beta agonist.


  • Mean change from baseline to Week 12 in FEV1 in patients with baseline eosinophils ≥300 cells/μL was the primary endpoint in Trial 1.
  •  
  • aSevere exacerbations were defined as deterioration of asthma requiring the use of systemic corticosteroids for at least 3 days or hospitalization or emergency room visit due to asthma that required systemic corticosteroids.
  •  
  • EOS, eosinophils; ICS, inhaled corticosteroid; SOC, standard of care.

EOSINOPHIL COUNTS ≥300 CELLS/μL:
Significantly reduced rate of severe exacerbations when added to SOC (secondary endpoint)a

Severe exacerbations through Week 52
BASELINE BLOOD EOS ≥300 CELLS/µL

SOC=medium- or high-dose ICS and a minimum of 1 and up to 2 additional controller medications.

  •  
  • Annualized rate of severe exacerbation events during the 52-week treatment period and mean change from baseline to Week 12 in FEV1 in the overall population were primary endpoints in Trial 2.

Severe Exacerbation Results: Trial 2

When added to maintenance therapy
DUPIXENT had a significant effect on severe exacerbations in patients with baseline blood eosinophils ≥150 cells/µLa

OVERALL POPULATION (primary analysis population): Significantly reduced rate of severe exacerbations when added to SOC (primary endpoint)b,c

Trial 2
Overall Population

In subjects with baseline blood eosinophil counts <150 cells/µL, similar severe exacerbation rates were observed between DUPIXENT and placebo.



  • Mean change from baseline to Week 12 in FEV1 in the overall population was a coprimary endpoint in Trial 2.
  •  
  • aThe effect was greater with increasing baseline blood eosinophil levels.
  • bOverall population was unrestricted by minimum baseline blood eosinophil count.
  • cSevere exacerbations were defined as deterioration of asthma requiring the use of systemic corticosteroids for at least 3 days or hospitalization or emergency room visit due to asthma that required systemic corticosteroids.

Greater reduction in severe exacerbation rates with increasing baseline blood eosinophil levels in prespecified subgroup analyses

Relative risk in annualized event rate of severe exacerbations across baseline blood eosinophil counts
TRIAL 2

Lung Function Results

When added to maintenance therapy
DUPIXENT significantly improved lung function (pre-bronchodilator FEV1)

EOSINOPHIL COUNTS ≥300 CELLS/µL (primary analysis population, Trial 1): Significant improvement seen at Week 12 (primary endpoint) and at Week 24 (secondary endpoint) when added to SOC

Change in lung function through Week 24
BASELINE BLOOD EOS ≥300 CELLS/µL
At Week 12 in patients with eosinophil counts ≥300 cells/µL:
  • 430 mL improvement from baseline in pre-bronchodilator FEV1 with DUPIXENT 200 mg + SOC
    vs 180 mL improvement with placebo + SOC (LS mean difference: 260 mL [95% CI: 110, 400 mL])
  • 390 mL improvement from baseline in pre-bronchodilator FEV1 with DUPIXENT 300 mg + SOC
    vs 180 mL improvement with placebo + SOC (LS mean difference: 210 mL [95% CI: 60, 360 mL])


  • LS, least squares.

EOSINOPHIL COUNTS ≥300 CELLS/μL: Significant improvement seen at Week 12 (secondary endpoint)

Change in lung function through Week 52
BASELINE BLOOD EOS ≥300 CELLS/µL
At Week 12 in patients with eosinophil counts ≥300 cells/µL:
  • 430 mL improvement from baseline in pre-bronchodilator FEV1 with DUPIXENT 200 mg + SOC
    vs 210 mL improvement with placebo + SOC (LS mean difference: 210 mL [95% CI: 130, 290 mL])
  • 470 mL improvement from baseline in pre-bronchodilator FEV1 with DUPIXENT 300 mg + SOC
    vs 220 mL improvement with placebo + SOC (LS mean difference: 240 mL [95% CI: 160, 320 mL])

Lung Function Results: Trial 2

When added to maintenance therapy
DUPIXENT had a significant effect on lung function (pre-bronchodilator FEV1) in patients with baseline blood eosinophils ≥150 cells/μL

OVERALL POPULATION: Significant improvement seen at Week 12 (primary endpoint) and through Week 52 when added to SOCa



TRIAL 2
OVERALL POPULATION





In Trial 2, a significant difference was not observed in change in FEV1 in patients with baseline blood eosinophil levels <150 cells/μL.



  • aOverall population was unrestricted by minimum baseline blood eosinophil count.

Greater improvement in lung function (pre-bronchodilator FEV1) with increasing baseline blood eosinophil levels in prespecified subgroup analyses

LS mean difference in change from baseline vs placebo to Week 12 in pre-bronchodilator FEV1 across baseline blood eosinophil counts


TRIAL 2


OCS Reduction Results: Trial 3

In OCS-dependent patients
DUPIXENT significantly reduced OCS dose while maintaining asthma control, irrespective of baseline blood eosinophil levels

OCS-DEPENDENT OVERALL POPULATION: Significantly reduced use of maintenance OCS while maintaining asthma control in Trial 3 (primary endpoint)a,b

Percent reduction from baseline of the final OCS dose at Weeks 20-24 while maintaining asthma control
OVERALL POPULATION

SOC=daily OCS in addition to regular use of high-dose ICS plus an additional controller.



OCS reduction secondary endpoints




  • aOverall population was unrestricted by minimum baseline blood eosinophil count.
  • bThe baseline mean OCS dose was 12 mg in the placebo group and 11 mg in the group receiving DUPIXENT.
  •  
  • OR, odds ratio.

Additional Secondary Endpoints

In OCS-dependent patients
DUPIXENT significantly reduced severe exacerbation rates and improved lung function, irrespective of baseline blood eosinophil levels



OCS-DEPENDENT OVERALL POPULATIONa-c


Effects on lung function and on oral steroid and exacerbation reduction were similar irrespective of baseline blood eosinophil levels.

The only biologic with an FDA approval for oral corticosteroid-dependent asthma,
regardless of phenotype

  • aOverall population was unrestricted by minimum baseline blood eosinophil count.
  • bAsthma exacerbation was defined as a temporary increase in OCS dose for at least 3 days.
  • cChange from baseline in pre-bronchodilator FEV1 at Week 24 was reported to allow time for OCS reduction to reach optimization.

ASTHMA CONTROL: ACQ-5

DUPIXENT significantly improved asthma control as measured by ACQ-5

ACQ-5 responder rates observed at Week 52 in Trial 2a,b



TRIAL 2
EOSINOPHIL COUNTS ≥300 CELLS/µL




TRIAL 2
OVERALL POPULATIONc

  • 69% of patients improved in ACQ-5 with DUPIXENT 200 mg + SOC vs
    62% of patients improved with placebo + SOC (OR: 1.37 [95% CI: 1.01, 1.86])

  • 69% of patients improved in ACQ-5 with DUPIXENT 300 mg + SOC vs
    63% of patients improved with placebo + SOC (OR: 1.28 [95% CI: 0.94, 1.73])


  • aResponder rates were defined as an improvement in score of 0.5 or more (scale ranged from 0 to 6 for ACQ-5 and 1 to 7 for AQLQ[S]).
  • bACQ-5: 5-item Asthma Control Questionnaire, a patient-reported measure of asthma control. Higher scores indicate less asthma control; a global score is calculated ranging from 0 to 6. The meaningful clinically important difference is 0.5.
  • cOverall population was unrestricted by minimum baseline blood eosinophil count.

Quality of Life AQLQ(S)

DUPIXENT significantly improved quality of life as measured by AQLQ(S)

AQLQ(S) responder rates observed at Week 52 in Trial 2a,b



TRIAL 2
EOSINOPHIL COUNTS ≥300 CELLS/µL




TRIAL 2
OVERALL POPULATIONc

  • 62% of patients improved in AQLQ(S) with DUPIXENT 200 mg + SOC vs
    54% of patients improved with placebo + SOC (OR: 1.61 [95% CI: 1.17, 2.21])

  • 62% of patients improved in AQLQ(S) with DUPIXENT 300 mg + SOC vs
    57% of patients improved with placebo + SOC (OR: 1.33 [95% CI: 0.98, 1.81])


  • aResponder rates were defined as an improvement in score of 0.5 or more (scale ranged from 0 to 6 for ACQ-5 and 1 to 7 for AQLQ[S]).
  • bAQLQ(S): Asthma Quality of Life Questionnaire, Standardized Version, a patient-reported measure of asthma-related quality of life. Higher scores indicate better quality of life; a global score is calculated ranging from 1 to 7. The meaningful clinically important difference is 0.5.
  • cOverall population was unrestricted by minimum baseline blood eosinophil count.

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Reference: DUPIXENT Prescribing Information. October 2018.