DUPIXENT®

Efficacy and burden data

Improvement in nasal congestion sustained over 52 weeks^1–4

DUPIXENT improved NC score vs placebo as early as Day 2 (post-hoc analysis),^d with significant results at Week 24 (primary endpoint) and sustained through Week 52 in patients receiving INCS^1⁠–4

Change in NC score through Week 52 in SINUS-52 (secondary endpoint)^1,2

CI, confidence interval; INCS, intranasal corticosteroids; LSM, least squares mean; NC, nasal congestion; Q2W, every 2 weeks

Week 24 (primary endpoint): −1.25-point improvement from a baseline score of 2.46 with DUPIXENT (n=295, pooled DUPIXENT arms^e) vs −0.38-point improvement from a baseline score of 2.38 with placebo (n=153; LSM difference −0.87, 95% CI −1.03 to −0.71; P<0.0001)^1,2

Week 52 (secondary endpoint): −1.35‑point improvement from a baseline score of 2.48 with DUPIXENT (n=150) vs −0.37-point improvement from a baseline score of 2.38 with placebo (n=153; −0.98, 95% CI −1.17 to −0.79; P<0.0001)^1,2

^dPooled SINUS-24/SINUS-52 Day 1 LSM difference between DUPIXENT (n=438) and placebo (n=286): –0.07 (95% CI –0.13 to –0.01; nominal P<0.05).^4
eBoth DUPIXENT arms in SINUS-52 received DUPIXENT 300 mg Q2W from baseline to Week 24.²

NC score is a patient-reported scale rating the severity of nasal blockage, from 0 = no symptoms to 3 = severe symptoms.²

The first biologic to report a >2‑point NPS improvement in Phase 3 trials^1,6,7

DUPIXENT significantly reduced the size of nasal polyps vs placebo, as measured by bilateral endoscopic NPS, as early as Week 4 (post-hoc analysis)^f and sustained through Week 52, in patients receiving INCS^1–3

Week 24 (primary endpoint): −1.71-point improvement in NPS from a baseline score of 6.18 with DUPIXENT (n=295, pooled DUPIXENT arms) vs 0.10-point worsening from a baseline score of 5.96 with placebo (n=153; LSM difference −1.80, 95% CI −2.10 to −1.51; P<0.0001)^1,2

Week 52 (secondary endpoint): −2.24-point improvement in NPS from a baseline score of 6.07 with DUPIXENT (n=150) vs 0.15-point worsening from a baseline score of 5.96 with placebo (n=153; LSM difference −2.40, 95% CI −2.77 to −2.02; P<0.0001)^1,2

^fSINUS-52 Week 4 LSM difference between DUPIXENT (n=295, pooled DUPIXENT arms) and placebo (n=153): −1.15 (95% CI, −1.40 to −0.91; nominal P<0.0001).³ 
Both DUPIXENT arms in SINUS-52 received DUPIXENT 300 mg Q2W from baseline to Week 24.²

Bilateral endoscopic NPS is a grading system used during nasal endoscopy to quantify the size and extent of nasal polyps in each nasal cavity. Each cavity is scored from 0 (no polyps) to 4 (polyps completely obstructing the nasal cavity). The bilateral score is the sum of both sides, ranging from 0 to 8.¹⁰

Patients regained smell as early as Day 3 (post-hoc analysis)^g,3

DUPIXENT improved loss of smell score (LoS) as early as Day 3^g (post-hoc analysis) vs placebo, and improved sense of smell, as measured by UPSIT score, from Week 2^h (post-hoc analysis) sustained through Week 52, in patients receiving INCS^1–4

Change in UPSIT score through Week 52 in SINUS-52 (secondary endpoint)³

CI, confidence interval; INCS, intranasal corticosteroids; LSM, least squares mean; Q2W, every 2 weeks; UPSIT, University of Pennsylvania Smell Identification Test
LoS is a patient‑collected assessment of the daily symptom severity of decreased or loss of smell, from (0 no symptoms) to 3 (severe symptoms).⁴
UPSIT is a standardised 40-item scratch-and-sniff test in which patients identify odours from multiple-choice options, yielding a score from 0 to 40.⁴

SINUS-52: 79.4% (n=228/287) of patients in the pooled DUPIXENT arms had anosmia (UPSIT score ≤18) at baseline, which was reduced to 30.0% (n=84/280) at Week 24, with almost no change observed in the placebo group (76.7% [n=115/150] at baseline vs 76.6% [n=111/145] at Week 24).²

^gPooled SINUS-24/SINUS-52 Day 3: LSM difference between DUPIXENT (n=438) and placebo (n=286); –⁠0.07 (95% difference CI –0.12 to –0.02; nominal P<0.01).^4
hPooled SINUS-24/SINUS-52 Week 2: DUPIXENT (n=438) significantly improved UPSIT scores from baseline by an LSM difference of 6.81 (95% CI 5.90 to 7.73) vs 1.28 (95% CI 0.23 to 2.33) in the placebo group (n=286) (nominal P<0.001).^4
iBoth DUPIXENT arms in SINUS-52 received DUPIXENT 300 mg Q2W from baseline to Week 24.²

Less surgery for a majority of patients²

In a prespecified pooled analysis, DUPIXENT significantly reduced the need for sinus surgery vs placebo over 52 weeks in patients receiving INCS²

1.1% required rescue nasal polyp surgery with DUPIXENT (pooled DUPIXENT Q2W arms, n=438) vs 7.7% with placebo (pooled placebo, n=286) (hazard ratio [HR] 0.174; 95% CI 0.066 to 0.462)^i,1,2

DUPIXENT targets type 2 inflammation to reduce the need for systemic steroids²

In a prespecified pooled analysis, DUPIXENT reduced the need for systemic steroids vs placebo over 52 weeks in patients receiving INCS²

9.4% required rescue systemic corticosteroids with DUPIXENT (pooled DUPIXENT Q2W arms, n=438) vs 30.8% with placebo (pooled placebo, n=286) (HR 0.261; 95% Cl 0.179 to 0.379)^i,1,2

ⁱFor the proportion of patients requiring systemic corticosteroids or nasal polyp surgery (actual or planned) during the treatment period, the entire DUPIXENT Q2W treatment period was pooled (group A up to 52 weeks and B up to 24 weeks from SINUS-52 and the DUPIXENT group from SINUS-24) from both studies, and a forced censor was included for the SINUS-52 group B at week 24. The entire placebo treatment period, of up to 52 weeks for SINUS-52 and up to 24 weeks for SINUS-24, was pooled as well.^1,2

Patients reported improved symptoms and HRQoL^1,2

DUPIXENT significantly decreased SNOT-22 scores vs baseline at Week 24^k sustained through Week 52, in patients receiving INCS²

Change in SNOT‑22 score through Week 52 in SINUS-52 (secondary endpoint)²

The maximum SNOT‑22 score is 110.²⁶
The meaningful clinically important difference is 8.9. Lower scores indicate better health‑related quality of life.²⁷

CI, confidence interval; INCS, intranasal corticosteroids; LSM, least squares mean; Q2W, every 2 weeks; SNOT ‑22, 22 ‑item Sinonasal Outcome Test

DUPIXENT significantly decreased SNOT-22 score vs placebo as early as Week 8 (post-hoc analysis)^J,2

^jPooled SINUS‑24/SINUS‑52 Week 8 (post-hoc analysis): DUPIXENT (n=438) significantly improved SNOT‑22 scores vs placebo by an LSM difference of –14.8 (95% CI –17.4 to –12.2: P<0.0001).^3
kWeek 24 ( SINUS‑52): –27.77 improvement from a baseline score of 50.16 with DUPIXENT vs –10.40 improvement from a baseline score of 53.46 with placebo (LSM difference: –17.36 [95% CI –20.87 to –⁠13.85]: p<0.0001).^1,2

SNOT-22 questionnaire is a patient‑reported assessment of 22 symptoms and consequences of CRSwNP:²⁶

ABBREVIATIONS
ACQ-6, six-item Asthma Control Questionnaire; CI, confidence interval; CRSwNP, chronic rhinosinusitis with nasal polyps; EPOS, European Position Paper on Rhinosinusitis and Nasal Polyps 2020; EUFOREA, European Forum for Research and Education in Allergy and Airway; FEV₁, forced expiratory volume in 1 second; HRQoL, health‑related quality of life; ICAR‑RS, International Consensus Statement on Allergy and Rhinology; IL‑4/13, interleukin‑4/13; INCS, intranasal corticosteroids; LoS, loss of smell score; LSM, least squares mean; LMK‑CT, Lund‑Mackay computed tomography; NC, nasal congestion/obstruction; NP, nasal polyps; NPS, nasal polyp score; OCS, oral corticosteroids; OSN, olfactory sensory neurons; Q2/4W, every 2/4 weeks; SD, standard deviation; SNOT‑22, 22‑item Sinonasal Outcome Test; UPSIT, University of Pennsylvania Smell Identification Test

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