DUPIXENT +
SOC
200 mg Q2Wa (n=150)
Placebo + SOC (n=158)
DUPIXENT + SOC
300 mg Q2Wb (n=157)
Placebo + SOC (n=158)
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
Subjects enrolled in DRI12544 were required to have, within 1 year of trial enrollment, treatment with systemic corticosteroids for worsening asthma at least once, or ED visit or hospitalization for worsening asthma
Subjects continued background asthma therapy throughout the duration of the studies, except in VENTURE in which OCS dose was reduced every 4 weeks during the OCS reduction phase (Weeks 4-20), as long as asthma control was maintained
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 24-week treatment periodc
DUPIXENT +
SOC
200 mg Q2Wa (n=631)
Placebo + SOC (n=317)
DUPIXENT + SOC
300 mg Q2Wb (n=633)
Placebo + SOC (n=321)
Pediatric subjects (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 were excluded
Subjects enrolled in QUEST were required to have, within 1 year of trial enrollment, treatment with systemic corticosteroids for worsening asthma at least once, or ED visit or hospitalization for worsening asthma
Subjects continued background asthma therapy throughout the duration of the studies, except in VENTURE in which OCS dose was reduced every 4 weeks during the OCS reduction phase (Weeks 4-20), as long as asthma control was maintained
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
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 ACQ‑5 and AQLQ(S) scores
Mean change from baseline to
Week 12 in
FEV1 in patients with FeNO ≥25 ppb and in patients with IgE
≥30 IU/mL and baseline blood eosinophil levels ≥300 cells/μL
Annualized rate of severe exacerbation events during the
52‑week treatment period in patients with FeNO ≥25 ppb
and in patients with IgE
≥30 IU/mL and baseline blood eosinophil levels ≥300 cells/μL
DUPIXENT + SOC +
OCS
300 mg Q2Wb (n=103)
Placebo + SOC + OCS (n=107)
Subjects (≥12 years) with
asthma who required daily
OCS in addition to regular
use of standard of care of
high-dose ICS and a minimum of 1
and up to 2 additional controller
medications; subjects with
baseline blood eosinophil
levels >1500 cells/μL were excluded
Subjects continued background asthma therapy throughout the duration of the studies, except in VENTURE in which OCS dose was reduced every 4 weeks during the OCS reduction phase (Weeks 4-20), as long as asthma control was maintained
Percent reduction from baseline in OCS dose at Week 24, while maintaining asthma control, in the overall population
Annualized rate of severe exacerbation events during the 24-week treatment period
Mean change from baseline to
Week 24 in FEV1
aWith 400 mg loading dose.1
bWith 600 mg loading dose.1
cResults were evaluated in the overall population and subgroups based on baseline blood eosinophil count.1
ACQ-5, Asthma Control Questionnaire, 5-item version; AQLQ(S), Asthma Quality of Life Questionnaire, Standardized Version; ED, emergency department; EOS, eosinophil; FeNO, fractional exhaled nitric oxide; FEV1, forced expiratory volume in 1 second; ICS, inhaled corticosteroid; LABA, long-acting beta agonist; LSM, least squares mean; OCS, oral corticosteroid; Q2W, once every 2 weeks; SCS, systemic corticosteroid; SOC, standard of care.
DUPIXENT 300 mg group (n=72) and placebo group (n=37), respectively: mean ages 51 ± 13 and 49 ± 12 years; 64% and 59% female; mean FeNO 63 ppb ± 40 and 53 ppb ± 25; mucus plug score 7.2 ± 5.1 and 6.9 ± 5.0; pre-bronchodilator FEV1 1900 mL ± 700 mL and 1900 mL ± 700 mL.
Background therapy: medium-to-high dose ICS + second controller ± third controller
dCT scans.5
Primary endpoints: Proportion of patients achieving FeNO <25 ppb at Week 24, and percent change from baseline to Week 24 in (s)iVaw at TLC.5
Select secondary and other endpoints: Change from baseline in pre-bronchodilator FEV1 at Week 24, and change from baseline in mucus plug score at Week 24 and CT scans of mucus plug volume (exploratory).5
The primary imaging endpoint ([s]iVaw at TLC) did not reach statistical significance (P>0.05); therefore all subsequent endpoints are descriptive; definitive conclusions cannot be made.5
What is functional respiratory imaging (FRI)?
ACQ-5, Asthma Control Questionnaire, 5-item version; CT, computed tomography; EOS, eosinophil; EOT, end of treatment; FeNO, fractional exhaled nitric oxide; FEV1, forced expiratory volume in 1 second; ICS, inhaled corticosteroid; OLE, open-label extension; Q2W, once every 2 weeks; (s)iVaw, specific image-based airway volume; TLC, total lung capacity.
TRAVERSE (N=2284), 48 to 96 weeks
| Treatment |
DUPIXENT + SOC
|
DUPIXENT + SOC
|
Subjects were initially enrolled for a 96-week treatment period;
however, an amendment was issued to shorten the treatment period
to |
| Study population |
|
||
| Primary endpoint |
Proportion of patients experiencing any TEAEs up to Week 96 of the OLE in populations from DRI12544, QUEST, EXPEDITION, and VENTURE |
||
| Select other endpoints |
|
||
| Exclusion criteria |
Subjects who developed a new medical condition, suffered a change in status of an established medical condition, developed a laboratory abnormality, or required a new treatment or medication during the screening period that would adversely affect participation in the study or require discontinuation of study medicationg |
||
There are limitations associated with open-label study design, including lack of comparator arm, decreasing sample size, and potential continued involvement of responders and attrition of nonresponders.
e Total number of subjects enrolled and exposed to treatment in OLE.7
f Total number of subjects who continued to be exposed to treatment beyond 48 weeks.7
g Exclusion criteria of
parent studies also applied, including pregnant/breastfeeding women, alcohol/drug abuse,
clinically significant comorbidity/lung disease other than asthma, smoking, and lung disease
that would impair lung function tests (eg, COPD).7
Patients enrolled from DRI12544 and QUEST (n=2062): Mean duration of asthma: 21 years; never smoked: 80%; mean exacerbations in previous year: 2.2; high-dose ICS use: 55%; pre-dose FEV1 at baseline: 1.79 L; percent reversibility: 26%; atopic medical history, overall: 82%; atopic dermatitis: 10%; nasal polyposis: 13%; allergic rhinitis: 67%; mean FeNO: 36 ppb; mean total IgE: 438 IU/mL; and mean baseline blood eosinophil count: 360 cells/μL.
Patients enrolled from VENTURE (n=187): Mean duration of asthma: 21 years; never smoked: 82%; mean exacerbations in previous year: 2.0; high-dose ICS use: 91%; pre-dose FEV1 at baseline: 1.58 L; percent reversibility: 20%; atopic medical history, overall: 73%; atopic dermatitis: 8%; nasal polyposis: 20%; allergic rhinitis: 58%; mean FeNO: 37 ppb; mean total IgE: 451 IU/mL; and mean baseline blood eosinophil count: 350 cells/μL.
COPD, chronic obstructive pulmonary disease; EOS,eosinophil; FeNO, fractional exhaled nitric oxide; FEV1, forced expiratory volume in 1 second; ICS, inhaled corticosteroid; LABA, long-acting beta agonist; LTRA, leukotriene receptor antagonist; OCS, oral corticosteroid; OLE, open-label extension; Q2W, once every 2 weeks; SOC, standard of care; TEAE, treatment-emergent adverse event.