DUPIXENT was studied in >2200 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
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 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: 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
-
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 DRI12544 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 DRI12544, 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/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).1
Consistently reduced asthma exacerbations1,5,h
Exacerbation reduction through weeks 48 to 96
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
- 79.5% of patients from DRI12544 (n=396) experienced zero exacerbations during Weeks 48-961
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.
Sustained breathing relief patients can feel up to ~3 years1,5-7
Lung function improvement sustained in patients from QUEST (ITT) enrolled in Traversek,l
Mean
absolute
pre-BD
FEV 1 (mL)
- 2150
- 2100
- 2050
- 2000
- 1950
- 1900
- 1850
- 1800
- 1750
- WEEKS:
- YEARS:
- 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
AT WEEK 96m
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.5
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.
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 endpoint)
- 88% reduction in OCS dose in the DUPIXENT/DUPIXENT group in patients rolled over from the VENTURE study at Week 96 (n=19)
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.
Demonstrated long-term safety data1,3,5
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 (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 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
- In DRI12544 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.