STUDY DESIGNS
IN PATIENTS 12+ YEARS

DUPIXENT enrolled a diverse
moderate‑to‑severe adult and pediatric
asthma patient population (12+ years) across
3 clinical trials1-5

DRI12544(N=776) 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)

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

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

The total population of patients in DRI12544, QUEST, and VENTURE was unrestricted by minimum baseline blood eosinophil count. In QUEST and VENTURE, 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.

Primary endpoint(s)

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

Other endpoint(s)

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

QUEST(N=1902) 52 WEEKS
Randomized

DUPIXENT + SOC
200 mg Q2Wa (n=631)
Placebo + SOC (n=317)

DUPIXENT + SOC
300 mg Q2Wb (n=633)
Placebo + SOC (n=321)

Study population

Pediatric patients (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

The total population of patients in DRI12544, QUEST, and VENTURE was unrestricted by minimum baseline blood eosinophil count. In QUEST and VENTURE, 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.

Primary endpoint(s)

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

Other endpoint(s)

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

VENTURE(N=210) 24 WEEKS
Randomized

DUPIXENT + SOC + OCS
300 mg Q2Wb (n=103)
Placebo + SOC + OCS (n=107)

Study population

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

The total population of patients in DRI12544, QUEST, and VENTURE was unrestricted by minimum baseline blood eosinophil count. In QUEST and VENTURE, 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.

Primary endpoint(s)

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

Other endpoint(s)

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.

bWith 600 mg loading dose.

cResults were evaluated in the overall population and subgroups based on baseline blood eosinophil count.

Baseline Demographics in DRI12544, QUEST, & VENTURE

DRI12544(N=776) 24 WEEKS
Mean age (SD),
years
49 (13)
Female, %
63
White, %
78
Mean duration
of asthma
(±SD), years
22 (15)
Never smoked,
%
77
Mean
exacerbations
in previous year
(±SD)
2.2 (2.1)
High-dose ICS
use, %
50
Pre-dose FEV1
at baseline
(±SD), L
1.84 (0.54)
Mean percent
predicted FEV1
at baseline
(±SD), %
61 (11)
Percent
reversibility
(±SD)
27 (15)
Atopic medical
history,
% overall
73
(atopic
dermatitis, %)
(8)
(nasal
polyposis, %)
(11)
(allergic
rhinitis, %)
(62)
Mean FeNO
(±SD), ppb
39 (35)
Mean total IgE
(±SD), IU/mL
435 (754)
Mean
baseline blood
eosinophil
count (±SD),
cells/µL
350 (430)
QUEST(N=1902) 52 WEEKS
Mean age (SD),
years
48 (15)
Female, %
63
White, %
83
Mean duration
of asthma
(±SD), years
21 (15)
Never smoked,
%
81
Mean
exacerbations
in previous year
(±SD)
2.1 (2.2)
High-dose ICS
use, %
52
Pre-dose FEV1
at baseline
(±SD), L
1.78 (0.60)
Mean percent
predicted FEV1
at baseline
(±SD), %
58 (14)
Percent
reversibility
(±SD)
26 (22)
Atopic medical
history, %
overall
78
(atopic
dermatitis, %)
(10)
(nasal
polyposis, %)
(13)
(allergic
rhinitis, %)
(69)
Mean FeNO
(±SD), ppb
35 (33)
Mean total IgE
(±SD), IU/mL
432 (747)
Mean baseline
blood
eosinophil
count (±SD),
cells/µL
360 (370)
VENTURE(N=210) 24 WEEKS
Mean age (SD),
years
51 (13)
Female, %
61
White, %
94
Mean duration
of asthma
(±SD), years
20 (14)
Never smoked,
%
81
Mean
exacerbations
in previous year
(±SD)
2.1 (2.2)
High-dose ICS
use, %
89
Pre-dose FEV1
at baseline
(±SD), L
1.58 (0.57)
Mean percent
predicted FEV1
at baseline
(±SD), %
52 (15)
Percent
reversibility
(±SD)
19 (23)
Atopic medical
history, %
overall
72
(atopic
dermatitis, %)
(8)
(nasal
polyposis, %)
(21)
(allergic rhinitis,
%)
(56)
Mean FeNO
(±SD), ppb
38 (31)
Mean total IgE
(±SD), IU/mL
431 (776)
Mean baseline
blood
eosinophil
count (±SD),
cells/µL
350 (310)

TRAVERSE enrolled over 2200 asthma patients, evaluated up to ~3 years6,7

TRAVERSE (N=2284), 48 to 96 weeks

Randomized

DUPIXENT + SOC
300 mg Q2W
48 weeksd (n=2282)

DUPIXENT + SOC
300 mg Q2W
96 weekse (n=1906)

Subjects were initially enrolled for a 96-week treatment period; however, an amendment was issued to shorten the treatment period to
48 weeks for all patients who enrolled following the amendment

Study population

Pediatric patients (12-17 years) and adults (≥18 years) with moderate-to-severe asthma who completed the treatment period in a previous DUPIXENT asthma clinical study (QUEST, VENTURE, EXPEDITION) or subjects with asthma who completed the treatment and follow-up periods in the previous DUPIXENT asthma study DRI12544

Subjects were on a background dose of medium- or high-dose ICS, as maintained during the parent study in which they participated, in combination with a second controller medication (and OCS for subjects from VENTURE)

Subjects requiring a third controller medication (eg, LABA, LTRA, methylxanthine) were allowed to enroll

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

Number and annualized rate of severe exacerbation events

Forced expiratory volume in 1 second (FEV1) (L)

In the OCS-dependent population, percent reduction from baseline in OCS dose and proportions of patients achieving ≥50% reduction and completely tapering off OCS

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 medicationf

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.

Select demographics and baseline characteristics7

Patients enrolled from DRI12544 and QUEST (n=2062): Mean duration of asthma: 21 years; never smoked: 80%; mean exacerbations in previous year: 2.18; 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; 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: 2.04; 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; mean baseline blood eosinophil count: 350 cells/μL.

d Total number of subjects enrolled and exposed to treatment in OLE.6

e Total number of subjects who continued to be exposed to treatment beyond 48 weeks.6

f Exclusion criteria of parent studies also applied, including pregnant/breastfeeding women, alcohol/drug abuse, clinically significant comorbid/lung disease other than asthma, smoking, and lung disease that would impair lung function tests (eg, COPD).7

COPD, chronic obstructive pulmonary disease; LABA, long-acting beta agonist; LTRA, leukotriene receptor antagonist; OLE, open-label extension.

References:

  1. DUPIXENT Prescribing Information.
  2. Rabe KF, Nair P, Brusselle G, et al. Efficacy and safety of dupilumab in glucocorticoid-dependent severe asthma. N Engl J Med. 2018;378(26):2475-2485.
  3. Castro M, Rabe KF, Corren J, et al. Dupilumab improves lung function in patients with uncontrolled, moderate-to-severe asthma. ERJ Open Res. 2020;6(1):00204-2019. doi:10.1183/23120541.00204-2019
  4. Data on file, Sanofi US. Dupilumab/SAR231893.
  5. Corren J, Castro M, O’Riordan T, et al. Dupilumab efficacy in patients with uncontrolled, moderate-to-severe allergic asthma. J Allergy Clin Immunol Pract. 2020;8(2):516-526.
  6. Wechsler ME, Ford LB, Maspero JF, et al. Dupilumab long-term safety and efficacy in patients with asthma: LIBERTY ASTHMA TRAVERSE. Poster presented at: 30th International Congress of the European Respiratory Society; September 7-9, 2020.
  7. Data on file, Sanofi US. LIBERTY ASTHMA TRAVERSE CSR, 2020.

Important Safety
Information and Indications

CONTRAINDICATION: DUPIXENT is contraindicated in patients with known hypersensitivity to dupilumab or any of its excipients.

WARNINGS AND PRECAUTIONS

Hypersensitivity: Hypersensitivity reactions, including anaphylaxis, serum sickness or serum sickness-like reactions, angioedema, generalized urticaria, rash, erythema nodosum, and erythema multiforme have been reported. If a clinically significant hypersensitivity reaction occurs, institute appropriate therapy and discontinue DUPIXENT.

Conjunctivitis and Keratitis: Conjunctivitis and keratitis occurred more frequently in atopic dermatitis subjects who received DUPIXENT compared to those who received placebo, with conjunctivitis being the most frequently reported eye disorder. Conjunctivitis also occurred more frequently in chronic rhinosinusitis with nasal polyposis subjects who received DUPIXENT compared to those who received placebo. Conjunctivitis and keratitis have been reported with DUPIXENT in postmarketing settings, predominantly in atopic dermatitis patients. Some patients reported visual disturbances (e.g. blurred vision) associated with conjunctivitis or keratitis. Advise patients to report new onset or worsening eye symptoms to their healthcare provider. Consider ophthalmological examination for patients who develop conjunctivitis that does not resolve following standard treatment or signs and symptoms suggestive of keratitis, as appropriate.

Eosinophilic Conditions: Patients being treated for asthma may present with serious systemic eosinophilia sometimes presenting with clinical features of eosinophilic pneumonia or vasculitis consistent with eosinophilic granulomatosis with polyangiitis (EGPA), conditions which are often treated with systemic corticosteroid therapy. These events may be associated with the reduction of oral corticosteroid therapy. Healthcare providers should be alert to vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy presenting in their patients with eosinophilia. Cases of eosinophilic pneumonia were reported in adult subjects who participated in the asthma development program and cases of vasculitis consistent with EGPA have been reported with DUPIXENT in adult subjects who participated in the asthma development program as well as in adult subjects with co-morbid asthma in the CRSwNP development program. A causal association between DUPIXENT and these conditions has not been established.

Acute Asthma Symptoms or Deteriorating Disease: Do not use DUPIXENT to treat acute asthma symptoms, acute exacerbations, acute bronchospasm or status asthmaticus. Patients should seek medical advice if their asthma remains uncontrolled or worsens after initiation of DUPIXENT.

Risk Associated with Abrupt Reduction of Corticosteroid Dosage: Do not discontinue systemic, topical, or inhaled corticosteroids abruptly upon initiation of DUPIXENT. Reductions in corticosteroid dose, if appropriate, should be gradual and performed under the direct supervision of a healthcare provider. Reduction in corticosteroid dose may be associated with systemic withdrawal symptoms and/or unmask conditions previously suppressed by systemic corticosteroid therapy.

Patients with Co-morbid Asthma: Advise patients with atopic dermatitis or CRSwNP who have co-morbid asthma not to adjust or stop their asthma treatments without consultation with their physicians.

Arthralgia: Arthralgia has been reported with the use of DUPIXENT with some patients reporting gait disturbances or decreased mobility associated with joint symptoms; some cases resulted in hospitalization. Advise patients to report new onset or worsening joint symptoms. If symptoms persist or worsen, consider rheumatological evaluation and/or discontinuation of DUPIXENT.

Parasitic (Helminth) Infections: It is unknown if DUPIXENT will influence the immune response against helminth infections. Treat patients with pre-existing helminth infections before initiating therapy with DUPIXENT. If patients become infected while receiving treatment with DUPIXENT and do not respond to anti-helminth treatment, discontinue treatment with DUPIXENT until the infection resolves. Helminth infections (5 cases of enterobiasis and 1 case of ascariasis) were reported in pediatric patients 6 to 11 years old in the pediatric asthma development program.

Vaccinations: Consider completing all age-appropriate vaccinations as recommended by current immunization guidelines prior to initiating DUPIXENT. Avoid use of live vaccines in patients treated with DUPIXENT.

ADVERSE REACTIONS:

  • Atopic dermatitis: The most common adverse reactions (incidence ≥1% at Week 16) in adult patients are injection site reactions, conjunctivitis, blepharitis, oral herpes, keratitis, eye pruritus, other herpes simplex virus infection, and dry eye. The safety profile in children and adolescents through Week 16 was similar to that of adults with atopic dermatitis. In an open-label extension study, the long-term safety profile of DUPIXENT in adolescents and children observed through Week 52 was consistent with that seen in adults with atopic dermatitis.
  • Asthma: The most common adverse reactions (incidence ≥1%) are injection site reactions, oropharyngeal pain, and eosinophilia.
  • Chronic rhinosinusitis with nasal polyposis: The most common adverse reactions (incidence ≥1%) are injection site reactions, eosinophilia, insomnia, toothache, gastritis, arthralgia, and conjunctivitis.

USE IN SPECIFIC POPULATIONS

  • Pregnancy: A pregnancy exposure registry monitors pregnancy outcomes in women exposed to DUPIXENT during pregnancy. To enroll or obtain information call 1‑877‑311‑8972 or go to https://mothertobaby.org/ongoing-study/dupixent/. Available data from case reports and case series with DUPIXENT use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. Human IgG antibodies are known to cross the placental barrier; therefore, DUPIXENT may be transmitted from the mother to the developing fetus.
  • Lactation: There are no data on the presence of DUPIXENT in human milk, the effects on the breastfed infant, or the effects on milk production. Maternal IgG is known to be present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for DUPIXENT and any potential adverse effects on the breastfed child from DUPIXENT or from the underlying maternal condition.

Please see accompanying full Prescribing Information.

Indications

Asthma: DUPIXENT is indicated as an add-on maintenance treatment of adult and pediatric patients aged 6 years and older with moderate-to-severe asthma characterized by an eosinophilic phenotype or with oral corticosteroid dependent asthma. Limitation of Use: DUPIXENT is not indicated for the relief of acute bronchospasm or status asthmaticus.

Chronic rhinosinusitis with nasal polyposis (CRSwNP): DUPIXENT is indicated as an add-on maintenance treatment in adult patients with inadequately controlled CRSwNP.

Atopic Dermatitis: DUPIXENT is indicated for the treatment of adult and pediatric patients aged 6 years and older with moderate-to-severe atopic dermatitis whose disease is not adequately controlled with topical prescription therapies or when those therapies are not advisable. DUPIXENT can be used with or without topical corticosteroids.