Demonstrated safety data and sustained efficacy across key measures of asthma control up to ~3 years.
The objectives of the TRAVERSE OLE (open-label extension) were as follows:
Patients who participated in a previous DUPIXENT asthma study were eligible for enrollment in the OLE study
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 dose.3
c With 600 mg loading dose.3,4
d Eligible patients completed the 16-week posttreatment 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
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 (eg, COPD).1
Patients Rolled Into TRAVERSE From QUEST (n=364)
The analyses of these data are not multiplicity controlled. Results are descriptive only.
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 QUEST and continued with DUPIXENT 300 mg Q2W + SOC in the OLE period (other endpoint)1
74% of patients from DRI12544 and QUEST experienced zero exacerbations over ~3 years of DUPIXENT1
97% of patients from DRI12544 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 DRI12544 and 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
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.
Results are descriptive.
Mean
absolute
pre-BD
FEV1 (mL)
k 1.78 L was the baseline FEV1 level from QUEST (n=633) compared with a placebo value of 1.75 L (n=321).6
l FEV1 was assessed in the exposed population (observed cases) using descriptive statistics. 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 in the parent study of 1.78 L.
330 mL improvement in FEV1 at Week 96 in the placebo/DUPIXENT group (n=219) from baseline in the parent study of 1.75 L for patients enrolled from QUEST.1,6
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.
Results are descriptive.
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 endpoint)
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.
Results are descriptive.
OCS reduction was at investigators’ discretion.
DUPIXENT demonstrated up to ~3 years of safety data in >2200 asthma patients
TEAEs occurring in ≥10% in any treatment group during the OLE period
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 (4) | |
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) |
Primary endpoint results: 86% of patients enrolled from DRI12544, 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
Long-term safety profile was consistent with that seen in the
placebo-controlled parent studies1BD, 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.
References:
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:
USE IN SPECIFIC POPULATIONS
Please see accompanying full Prescribing Information.
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.