Liberty Asthma Traverse

DUPIXENT WAS STUDIED IN AN OLE TO ASSESS LONG-TERM SAFETY AND EFFICACY IN ASTHMA

Demonstrated safety
data and sustained
efficacy across key
measures of asthma
control up to ~3 years

DUPIXENT was studied in >2000 asthma patients up to ~3 years1,2,a

The objectives of the TRAVERSE OLE (open-label extension) were as follows:

  • Primary Objective: To assess the long-term safety and tolerability of DUPIXENT
  • Select Secondary Objective: To assess the long-term efficacy of DUPIXENT

Patients who participated in a previous DUPIXENT asthma study were eligible for enrollment in the OLE study

TRAVERSE OLE Study (48 or 96 Weeks)

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.

a Subjects were initially enrolled for a 96-week treatment period; however, an amendment was issued to reduce the treatment period to 48 weeks for all patients who enrolled following the amendment.1

b With 400 mg loading dose3

c With 600 mg loading dose3,4

d Eligible patients completed the 16-week post-treatment follow-up period of the parent study before being rolled over into TRAVERSE.1

e Total number of subjects enrolled and exposed to treatment in OLE.2

f Total number of subjects who continued to be exposed to treatment beyond 48 weeks.2

  • Study Population: Adolescents (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 DRI (P2b)
  • Treatment Protocol: DUPIXENT 300 mg was administered subcutaneously every other week (Q2W) for up to 96 weeks, as an add-on to ICS in combination with other controller medications maintained from the parent study, including OCS for patients from the VENTURE studya
    • Patients enrolled from DRI were administered a loading dose of 600 mg dupilumab on Day 1
    • Patients 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 DRI (P2b), QUEST, EXPEDITION, and VENTURE
  • 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 medicationg

g Exclusion criteria of parent studies also applied, including pregnant/breast-feeding women, alcohol/drug abuse, clinically significant comorbid/lung disease other than asthma, smoking, and lung disease that would impair lung function tests (e.g., COPD).1

View Parent Studies Baseline Demographics

DUPIXENT demonstrated sustained asthma control up to ~3 years

Consistently reduced asthma exacerbations1,5,h

Exacerbation reduction through weeks 48 to 96 (Patients from QUEST)

89% of patients from QUEST experienced zero exacerbations in year 3

(Weeks 48-96) when treated with DUPIXENT 200 mg/300 mg Q2W + SOC (n=816) for 52 weeks in Trial 2 (QUEST) and continued with DUPIXENT 300 mg Q2W + SOC in the OLE period (other endpoint)1

  • 79.5% of patients from Trial 1 (DRI [P2b]) (n=396) experienced 0 exacerbations during Weeks 48-96.1

74% of patients from DRI and QUEST experienced 0 exacerbations over ~3 years of DUPIXENT1

97% of patients from DRI and QUEST did not have an exacerbation requiring hospitalization or ED visit

when treated with DUPIXENT 300 mg Q2W + SOC (n=2062) during the second and third years in the OLE period1,i,j

h Exacerbations were defined as deterioration of asthma requiring the use of systemic corticosteroids for at least 3 days or hospitalization or ED visit due to asthma that required systemic corticosteroids.3

i Analysis includes Trial 1 (DRI [P2b]) and Trial 2 (QUEST) patients enrolled in TRAVERSE.1

j Of the 542 patients who experienced at least 1 severe asthma exacerbation, 66 (3.2% of the overall study population) had an exacerbation that required hospitalization or ED visit during the TRAVERSE study period (unadjusted annualized event rate of 0.027).1

Results are descriptive.

Sustained breathing relief patients can feel up to ~3 years1,2,5,6

Lung function improvement sustained in patients from QUEST (ITT) enrolled in Traversek,l

Mean

Absolute

pre-BD

FEV 1

  • 2.15
  • 2.10
  • 2.05
  • 2.00
  • 1.95
  • 1.90
  • 1.85
  • 1.80
  • 1.75
  • WEEKS
  • YEARS
SWIPE TO SEE SUSTAINED
IMPROVEMENT
  • 0
  • 2
  • 4
  • 6
  • 8
  • 10
  • 12
  • 16
  • 20
  • 24
  • 28
  • 32
  • 36
  • 40
  • 44
  • 48
  • 0
  • 2
  • 4
  • 8
  • 12
  • 24
  • 48
  • 72
  • 84
  • 96
QUEST TRAVERSE
Year 1 Year 2 Year 3
310mL IMPROVEMENT
AT WEEK 96m
DUPIXENT 300 mg + SOC (n=447) Placebo + SOC

k 1.78 L was the baseline FEV1 level from Trial 2 (QUEST; n=633) compared with a placebo value of 1.75 L (n=321).5

l FEV1 was assessed in the exposed population (observed cases) using descriptive statistics. BL represents the baseline of the parent study, Week 0 (TRAVERSE) represents the start of the OLE, and Weeks refer to the time in OLE without regard to any time in any parent study.2

m Improvement in FEV1 at Week 96 (n=447) in the DUPIXENT/DUPIXENT group from baseline of 1.78 L in the parent study.

330 mL improvement in FEV1 at Week 96 in the placebo/DUPIXENT group (n=219) compared from baseline of 1.75 L in the parent study for patients enrolled from Trial 2 (QUEST).1,5

Results are descriptive.

ELIMINATED OR REDUCED OCS DOSE FOR UP TO ~3 YEARS1

79% of patients from VENTURE eliminated their OCS DOSE

A gradual increase in the number of patients eliminating their OCS dose was observed from 53.3% at Week 0 (n=48) to 59.6% at Week 48 (n=34) to 78.9% at Week 96 (n=15) in the DUPIXENT/DUPIXENT group (secondary endpoints)

88% reduction in OCS dose

in the DUPIXENT/DUPIXENT group in patients rolled over from the VENTURE study at Week 96 (n=19)

Results are descriptive.
OCS reduction was at investigators' discretion.

Demonstrated long-term safety data1-3

DUPIXENT demonstrated up to ~3 years of safety data in >2000 asthma patients

TEAEs occurring in ≥10% in any treatment group

Nasopharyngitis
DUPIXENT/DUPIXENT
(n=421) n (%)		 109 (26)
Placebo/DUPIXENT
(n=111) n (%)		 27 (24)
Bronchitis
DUPIXENT/DUPIXENT
(n=421) n (%)		 80 (19)
Placebo/DUPIXENT
(n=111) n (%)		 15 (14)
Upper respiratory tract infection
DUPIXENT/DUPIXENT
(n=421) n (%)		 60 (14)
Placebo/DUPIXENT
(n=111) n (%)		 18 (16)
Influenza
DUPIXENT/DUPIXENT
(n=421) n (%)		 45 (11)
Placebo/DUPIXENT
(n=111) n (%)		 5 (5)
Pharyngitis
DUPIXENT/DUPIXENT
(n=421) n (%)		 37 (9)
Placebo/DUPIXENT
(n=111) n (%)		 16 (14)
Headache
DUPIXENT/DUPIXENT
(n=421) n (%)		 47 (11)
Placebo/DUPIXENT
(n=111) n (%)		 13 (12)
Injection-site erythema
DUPIXENT/DUPIXENT
(n=421) n (%)		 55 (13)
Placebo/DUPIXENT
(n=111) n (%)		 26 (23)
Injection-site pruritus
DUPIXENT/DUPIXENT
(n=421) n (%)		 16 (14)
Placebo/DUPIXENT
(n=111) n (%)		 12 (11)
Nasopharyngitis
DUPIXENT/DUPIXENT
(n=1013) n (%)		 191 (19)
Placebo/DUPIXENT
(n=517) n (%)		 99 (19)
Bronchitis
DUPIXENT/DUPIXENT
(n=1013) n (%)		 118 (12)
Placebo/DUPIXENT
(n=517) n (%)		 63 (12)
Upper respiratory tract infection
DUPIXENT/DUPIXENT
(n=1013) n (%)		 130 (13)
Placebo/DUPIXENT
(n=517) n (%)		 65 (13)
Influenza
DUPIXENT/DUPIXENT
(n=1013) n (%)		 69 (7)
Placebo/DUPIXENT
(n=517) n (%)		 30 (6)
Pharyngitis
DUPIXENT/DUPIXENT
(n=1013) n (%)		 59 (6)
Placebo/DUPIXENT
(n=517) n (%)		 26 (5)
Headache
DUPIXENT/DUPIXENT
(n=1013) n (%)		 74 (7)
Placebo/DUPIXENT
(n=517) n (%)		 47 (9)
Injection-site erythema
DUPIXENT/DUPIXENT
(n=1013) n (%)		 50 (5)
Placebo/DUPIXENT
(n=517) n (%)		 35 (7)
Injection-site pruritus
DUPIXENT/DUPIXENT
(n=1013) n (%)		 7 (1)
Placebo/DUPIXENT
(n=517) n (%)		 15 (3)
Nasopharyngitis
DUPIXENT/DUPIXENT
(n=90) n (%)		 16 (18)
Placebo/DUPIXENT
(n=97) n (%)		 17 (18)
Bronchitis
DUPIXENT/DUPIXENT
(n=90) n (%)		 14 (16)
Placebo/DUPIXENT
(n=97) n (%)		 9 (9)
Upper respiratory tract infection
DUPIXENT/DUPIXENT
(n=90) n (%)		 6 (7)
Placebo/DUPIXENT
(n=97) n (%)		 8 (8)
Influenza
DUPIXENT/DUPIXENT
(n=90) n (%)		 7 (8)
Placebo/DUPIXENT
(n=97) n (%)		 9 (9)
Pharyngitis
DUPIXENT/DUPIXENT
(n=90) n (%)		 4 (4)
Placebo/DUPIXENT
(n=97) n (%)		 1 (1)
Headache
DUPIXENT/DUPIXENT
(n=90) n (%)		 5 (6)
Placebo/DUPIXENT
(n=97) n (%)		 4 (4)
Injection-site erythema
DUPIXENT/DUPIXENT
(n=90) n (%)		 2 (2)
Placebo/DUPIXENT
(n=97) n (%)		 5 (5)
Injection-site pruritus
DUPIXENT/DUPIXENT
(n=90) n (%)		 0
Placebo/DUPIXENT
(n=97) n (%)		 2 (2)
  • Other TEAEs occurred in ≥1% in any treatment group in TRAVERSE, including but not limited to oropharyngeal pain and eosinophilia1

Primary endpoint results: 86% of patients enrolled from DRI (P2b), 79% of patients enrolled from QUEST, and 77% of patients enrolled from VENTURE experienced at least one TEAE up to Week 96 of the OLE period.1

  • In DRI (P2b) and QUEST, the adverse reactions that occurred at a rate of at least 1% in subjects treated with DUPIXENT and at a higher rate than in their respective comparator groups were injection site reactions, oropharyngeal pain, and eosinophilia (6-month safety pool).3

Long-term safety profile was consistent with that seen in the placebo-controlled parent studies1

BD, bronchodilator; COPD, chronic obstructive pulmonary disease; ED, emergency department; FEV1, forced expiratory volume in 1 second; ICS, inhaled corticosteroid; ITT, intention-to-treat; LABA, long-acting beta agonist; LSM, least squares mean; LTRA, leukotriene receptor antagonist; OCS, oral corticosteroid; Q4W, once every 4 weeks; SOC, standard of care; TEAE, treatment-emergent adverse event.

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References:

  1. Data on file, Sanofi US. LIBERTY ASTHMA TRAVERSE CSR, 2020.
  2. 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.
  3. DUPIXENT Prescribing Information.
  4. Data on file, Sanofi US. EXPEDITION Amended Clincial Trial Protocol 2, 2016.
  5. Data on file, Sanofi US. QUEST CSR, 2017.
  6. Santanello NC, Zhang J, Seidenberg B, Reiss TF, Barber BL. What are minimal important changes for asthma measures in a clincical trial? Eur Respir J. 1999;14(1):23-27.

Important Safety
Information and Indication

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

WARNINGS AND PRECAUTIONS

Hypersensitivity: Hypersensitivity reactions, including generalized urticaria, rash, erythema nodosum, anaphylaxis and serum sickness or serum sickness-like reactions, were reported in <1% of subjects who received DUPIXENT in clinical trials. If a clinically significant hypersensitivity reaction occurs, institute appropriate therapy and discontinue DUPIXENT.

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. Physicians 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 patients who participated in the asthma development program and cases of vasculitis consistent with EGPA have been reported with DUPIXENT in adult patients who participated in the asthma development program as well as in adult patients with co-morbid asthma in the chronic rhinosinusitis with nasal polyposis 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.

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

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.

ADVERSE REACTIONS: The most common adverse reactions (incidence ≥1%) in patients with asthma are injection site reactions, oropharyngeal pain, and eosinophilia.

DRUG INTERACTIONS: Avoid use of live vaccines in patients treated with DUPIXENT.

USE IN SPECIFIC POPULATIONS

  • Pregnancy: There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to DUPIXENT during pregnancy. Healthcare providers and patients may call 1-877-311-8972 or go to https://mothertobaby.org/ongoing-study/dupixent/ to enroll in or obtain information about the registry. 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.


Indication

DUPIXENT is indicated as an add-on maintenance treatment in patients with moderate-to-severe asthma aged 12 years and older with 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.