B0202 - Dupilumab Treatment Leads to Rapid and Sustained Improvements in Dysphagia

Monday, October 24, 2022

10:00 AM – 12:00 PM ET

Location: Crown Ballroom

Presenting Author(s)

MR

Marc Rothenberg, MD, PhD

Cincinnati Children’s Hospital Medical Center and University of Cincinnati College of Medicine
Cincinnati, OH

Award: Presidential Poster Award

Marc Rothenberg, MD, PhD¹, Eilish McCann, PhD², Alain Schoepfer, MD³, Xian Sun, PhD², Tiffany Pela, MPH, PharmD⁴, Angela Khodzhayev, PharmD², Arpita Nag, MBA, MS, PhD⁴, Danen Cunoosamy, PhD⁵, Siddhesh Kamat, MS, MBA², Amr Radwan, MA, MBBChir², Juby Jacob-Nara, MD⁴
¹Cincinnati Children’s Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, OH; ²Regeneron Pharmaceuticals, Tarrytown, NY; ³Lausanne University Hospital, Lausanne, Vaud, Switzerland; ⁴Sanofi, Bridgewater, NJ; ⁵Sanofi, Cambridge, MA

Introduction: Eosinophilic esophagitis (EoE) is a chronic, type 2 inflammatory disease of the esophagus with substantially impaired quality of life; dysphagia symptoms are particularly burdensome. Dupilumab, a fully human monoclonal antibody, blocks the shared receptor component for IL-4/IL-13, key and central drivers of type 2 inflammation in EoE. In the 3-part LIBERTY-EoE-TREET phase 3 trial (NCT03633617), Parts A and B demonstrated that weekly (qw) dupilumab 300mg improved clinical, symptomatic, histologic, and endoscopic EoE aspects and was generally well tolerated in patients (pts) ≥12 years at Week 24; results from Part A were sustained up to 52 weeks in Part C. The objective of this analysis is to assess the effect of dupilumab vs placebo on the Dysphagia Symptom Questionnaire (DSQ) score through the 24-week double-blind treatment period and the 28-week extended treatment period of the EoE-TREET trial.

Methods: In Part A, 42 pts were randomized to dupilumab 300mg qw, and 39 to placebo. In Part B, 80 pts were randomized to dupilumab 300mg qw, and 79 to placebo for 24 weeks. From Part A, 40 dupilumab-treated and 37 placebo-treated pts continued to Part C and received dupilumab 300mg qw for an additional 28 weeks. The DSQ is a patient-reported outcome measure, comprising four questions on dysphagia; daily responses are collected and a biweekly total score calculated over 14 days ranging from 0-84 with higher scores indicating greater dysphagia frequency and severity.

Results: Baseline (BL) mean (standard deviation [SD]) DSQ scores in Parts A and B ranged from 32.2(12.66) to 38.4(10.70). The least squares mean change from BL in DSQ total score (standard error) for dupilumab vs placebo was –9.15(1.74) vs –3.50(1.88) in Part A (P=0.0166), and –12.32(1.40) vs –6.44(1.43) in Part B (P=0.0018) at Week 4; and –21.92(2.53) vs –9.60(2.79) in Part A (P=0.0004), and –23.78(1.86) vs –13.86(1.91) in Part B (P< 0.0001) at Week 24. In pts from Part A who continued to Part C, mean (SD) change in DSQ score from Part A BL was –23.44(16.15) for dupilumab/dupilumab pts and –21.71(17.14) for placebo/dupilumab pts.

Discussion: In Parts A and B of the EoE-TREET trial, treatment with dupilumab 300mg qw resulted in a significant improvement in DSQ score compared to placebo as early as Week 4 and maintained through Week 24; improvements observed after 24 weeks in Part A were maintained through 52 weeks in Part C. Placebo/dupilumab pts saw similar improvement in Part C as Part A dupilumab pts.

DSQ total score	Placebo	Dupilumab 300mg qw
Part A
N	39	42
Baseline, mean (SD)	35.1 (12.11)	32.2 (12.66)
Week 4, LS mean change (SE) LS mean difference (95% CI) P value vs placebo	–3.50 (1.88)	–9.15 (1.74) –5.65 (-10.28, -1.03) 0.0166
Week 24, LS mean change (SE) LS mean difference (95% CI) P value vs placebo	–9.60 (2.79)	–21.92 (2.53) –12.32 (–19.11, –5.54) 0.0004
Part B
N	79	80
Baseline, mean (SD)	36.1 (10.55)	38.4 (10.70)
Week 4, LS mean change (SE) LS mean difference (95% CI) P value vs placebo	–6.44 (1.43)	–12.32 (1.40) –5.88 (–9.58, –2.18) 0.0018
Week 24, LS mean change (SE) LS mean difference (95% CI) P value vs placebo	–13.86 (1.91)	–23.78 (1.86) –9.92 (–14.81, –5.02) < 0.0001
	Placebo/ Dupilumab 300mg qw	Dupilumab 300mg qw/ Dupilumab 300mg qw
Part A→C
N	37	40
Week 52, mean change from Part A baseline (SD)	–21.71 (17.14)	–23.44 (16.15)

Table: Table. Absolute change from baseline in DSQ total score during the 24-week double-blind treatment period and 28-week extended active treatment period of weekly dupilumab 300mg or placebo.
CI, confidence interval; LS, least squares; SD, standard deviation; SE, standard error; qw, weekly.

Disclosures:

Marc Rothenberg: Allakos – Consultant. AstraZeneca – Consultant. BMS – Consultant. ClostraBio – Consultant. ClostraBio – Stock Options. Mapi Research Trust – Royalties. PulmOne – Royalties. PulmOne – Stock Options. Spoon Guru – Consultant. Spoon Guru – Stock Options. Teva Pharmaceuticals – Royalties. UpToDate – Royalties.

Eilish McCann: Regeneron Pharmaceuticals, Inc. – Employee, Stock Options.

Alain Schoepfer: Adare Pharma Solutions – Consultant. Aptalis – Grant/Research Support. AstraZeneca – Grant/Research Support. BMS – Consultant. Dr. Falk Pharma – Consultant, Grant/Research Support. Ellodi Pharmaceuticals – Consultant. Gossamer Bio – Consultant. GSK – Grant/Research Support. Nestlé – Grant/Research Support. Novartis – Grant/Research Support. Receptos/BMS – Grant/Research Support. Regeneron Pharmaceuticals – Grant/Research Support. Sanofi – Consultant.

Xian Sun: Regeneron Pharmaceuticals, Inc. – Employee, Stock Options.

Tiffany Pela: Sanofi – Employee, Stock Options.

Angela Khodzhayev: Regeneron Pharmaceuticals – Employee, Stock Options.

Arpita Nag: Sanofi – Employee, Stock Options.

Danen Cunoosamy: Sanofi – Employee, Stock Options.

Siddhesh Kamat: Regeneron Pharmaceuticals – Employee, Stock Options.

Amr Radwan: Regeneron Pharmaceuticals – Employee, Stock Options.

Juby Jacob-Nara: Sanofi – Employee, Stock Options.

Marc Rothenberg, MD, PhD¹, Eilish McCann, PhD², Alain Schoepfer, MD³, Xian Sun, PhD², Tiffany Pela, MPH, PharmD⁴, Angela Khodzhayev, PharmD², Arpita Nag, MBA, MS, PhD⁴, Danen Cunoosamy, PhD⁵, Siddhesh Kamat, MS, MBA², Amr Radwan, MA, MBBChir², Juby Jacob-Nara, MD⁴. B0202 - Dupilumab Treatment Leads to Rapid and Sustained Improvements in Dysphagia, ACG 2022 Annual Scientific Meeting Abstracts. Charlotte, NC: American College of Gastroenterology.