P0198 - A Phase 2 Study Design to Investigate the Efficacy and Safety of Dupilumab Therapy Compared With Placebo in Adults With Moderately to Severely Active Ulcerative Colitis With an Eosinophilic Phenotype

Sunday, October 22, 2023

3:30 PM – 7:00 PM PT

Location: Exhibit Hall

Presenting Author(s)

Lila Glotfelty, MD, PhD (she/her/hers)

Sanofi
Springfield, VA

David Binion, MD¹, Brian G. Feagan, MD², Eric Mortensen, MD, PhD³, Elizabeth Laws, PhD⁴, Jennifer Maloney, MD³, Renata Martincova, MD⁴, Allen Radin, MD³, Lila Glotfelty, MD, PhD⁴
¹University of Pittsburgh Medical Center, Pittsburgh, PA; ²Western University, London, ON, Canada; ³Regeneron Pharmaceuticals Inc., Tarrytown, NY; ⁴Sanofi, Bridgewater, NJ

Introduction: Ulcerative colitis (UC) is a chronic inflammatory disease, heterogeneous in nature with many different drivers of pathogenesis, characterized by inflammation of the colon mucosa, relapsing–remitting disease course, and variable response to therapy. Despite the variety of molecular targeted agents available, the proportion of patients with UC refractory to these during the induction phase persists at 30–55%. Recent studies suggest that higher colonic eosinophil levels may be associated with increased disease activity, poorer clinical outcomes, and response to therapy.

Dupilumab (DPL), a fully human monoclonal antibody blocks the shared receptor component for interleukin IL-4 and IL-13, key and central drivers of type 2 inflammation in multiple diseases, including atopic dermatitis, asthma, chronic rhinosinusitis with nasal polyps, eosinophilic esophagitis, and prurigo nodularis. The Phase 2 LIBERTY-UC SUCCEED (NCT05731128) study is designed to investigate the efficacy and safety of DPL vs placebo (PBO) in adults with moderately to severely active UC with a Type 2 inflammatory phenotype as reflected by eosinophilia.

Methods: Patients will be randomized 1:1 to receive DPL or PBO. Key inclusion criteria include age ≥18 years, moderately to severely active UC (modified Mayo score 5–9), biomarker enrichment, and inadequate/non-response, loss of response, or intolerance to standard biologic therapy and/or oral corticosteroids, ASA compounds, immunomodulators, or small molecules. Key exclusion criteria include severe extensive colitis (current hospitalization, likely to require surgery for UC within 12 weeks of screening), prior medical history of eosinophilic colitis, or presence of intestinal failure.

Results: The primary endpoint is proportion of patients in clinical remission at Week 24, defined as a modified Mayo score of ≤2 with a stool frequency score ≤1, a rectal bleeding score = 0, and a Mayo endoscopic subscore ≤1 with absence of friability. Higher scores indicate greater disease severity. Secondary endpoints include the proportion of patients achieving clinical response by modified Mayo score at Week 8, 24, and 52, and incidence of treatment-emergent or serious adverse events.

Discussion: The Phase 2 LIBERTY-UC SUCCEED study will determine the efficacy and safety of DPL therapy in adults with moderately to severely active UC with a Type 2 phenotype. This will aid in addressing the need for precision medicine-directed approaches to treat UC.

Primary endpoint	Proportion of patients in clinical remission Clinical remission defined as a modified Mayo score of ≤2 with a stool frequency score ≤1, a rectal bleeding score = 0, and a Mayo endoscope subscore ≤1 with absence of friability	Week 24
Secondary efficacy endpoints	Proportion of patients achieving clinical response by modified Mayo score Proportion of patients achieving histologic–endoscopic healing Proportion of patients with a Mayo endoscopic subscore of 0 or 1 without friability Proportion of patients with a Mayo endoscopic subscore of 0 Change from baseline in Abdominal Pain NRS score	Weeks 8, 24, and 52
	Proportion of patients in clinical remission by modified Mayo score	Weeks 8 and 52
	Proportion of patients in clinical remission who are off concomitant OCS for ≥4 weeks prior Proportion of patients in clinical remission who are off concomitant OCS for ≥4 weeks prior who were receiving OCS at baseline	Week 52
	Normalized Enrichment Scores for the relative change in the EoE diagnostic panel transcriptome signature Normalized Enrichment Scores for the relative change in the type 2 inflammation transcriptome signature	Weeks 16 and 52
	Proportion of patients in symptomatic remission over time Symptomatic remission defined as Mayo stool frequency score = 0, or Mayo stool frequency score = 1 with a ≥1-point decrease from baseline, and Mayo rectal bleeding score = 0	During treatment period
Secondary safety endpoints	Incidence of treatment-emergent adverse events Incidence of treatment-emergent serious adverse events Concentration of dupilumab in serum over time Incidence of treatment-emergent ADAs against dupilumab	During treatment period and follow-up period
Secondary safety endpoints	Change from baseline in the NES in type 2 inflammation transcriptome signature	Weeks 24 and 52

Table: Table. Primary and secondary endpoints of the phase 2 LIBERTY-UC SUCCEED study

Disclosures:

David Binion: AbbVie – Consultant. Janssen – Consultant. Synthetic Biologics – Consultant. UCB Pharma – Consultant.

Brian Feagan: AbbVie – Advisory Committee/Board Member, Consultant, Speakers Bureau. AbolerIS – Consultant. AgomAB Therapeutics – Consultant. Allianthera – Consultant. Amgen – Advisory Committee/Board Member, Consultant. AnaptysBio – Consultant. Applied Molecular Transport Inc. – Consultant. Arena Pharma – Consultant. Avir – Consultant. Azora Therapeutics – Consultant. Baxter – Consultant. BioJamp – Consultant. Biora Therapeutics – Consultant. Boehringer Ingelheim – Advisory Committee/Board Member, Consultant. Boston Pharma – Consultant. Bristol Myers Squibb – Consultant. Celgene/BMS – Advisory Committee/Board Member, Consultant. Connect BioPharma – Consultant. Cytoki – Consultant. Disc Medicine – Consultant. Duality – Consultant. EcoR1 – Advisory Committee/Board Member, Consultant. Eli Lilly – Consultant. Equillium – Consultant. Ermium – Consultant. Everest Clinical Research Corp. – Consultant. Ferring Pharmaceuticals – Consultant. First Wave – Consultant. Galapagos – Consultant. Galen Atlantica – Consultant. Genentech/Roche – Advisory Committee/Board Member, Consultant. Gilead – Consultant. GlaxoSmithKline – Advisory Committee/Board Member, Consultant. Glenmark – Consultant. Gossamer Pharma – Consultant, stock shareholder. Hoffmann-LaRoche – Consultant. Hot Spot Therapeutics – Consultant. Imhotex – Consultant. ImmunExt – Consultant. Immunic Therapeutics – Consultant. Index Pharma – Advisory Committee/Board Member, Consultant. Intact Therapeutics – Consultant. JAKAcademy – Consultant. Janssen – Advisory Committee/Board Member, Consultant, Speakers Bureau. Japan Tobacco Inc. – Consultant. Kaleido Biosciences – Consultant. L.E.K. Consulting – Consultant. Landos Biopharma – Consultant. Leadiant – Consultant. LifeSci Capital – Consultant. Lument AB – Consultant. Millennium – Consultant. MiroBio – Consultant. Morphic Therapeutics – Advisory Committee/Board Member, Consultant. Mylan – Consultant. Novartis – Advisory Committee/Board Member. OM Pharma – Consultant. Origo BioPharma – Advisory Committee/Board Member, Consultant. Orphagen – Consultant. Otsuka – Consultant. Pandion Therapeutics – Consultant. Pfizer – Advisory Committee/Board Member, Consultant. Play to Know AG – Consultant. Progenity – Advisory Committee/Board Member, Consultant. Prometheus Therapeutics and Diagnostics – Advisory Committee/Board Member, Consultant. Protagonist – Consultant. PTM Therapeutics – Consultant. Q32 Bio – Consultant. Rebiotix – Consultant. RedHill Biopharma – Consultant. Redx – Consultant. Roche – Consultant. Sandoz – Consultant. Sanofi – Consultant. Seres Therapeutics – Consultant. Silverback Therapeutics – Consultant. Surrozen Inc. – Consultant. Takeda – Advisory Committee/Board Member, Consultant, Speakers Bureau. Teva – Advisory Committee/Board Member, Consultant. Thelium – Consultant. Theravance – Consultant. Tigenix – Consultant. Tillotts Pharma – Advisory Committee/Board Member, Consultant. UCB Pharma – Consultant. VHSquared Ltd. – Consultant. Viatris – Consultant. Western University, Alimentiv Inc – Employee. Ysios – Consultant. Ysopia – Consultant. Zealand Pharma – Consultant.

Eric Mortensen: Regeneron Pharmaceuticals Inc. – Employee, Shareholder.

Elizabeth Laws: Sanofi – Employee, Stock Options.

Jennifer Maloney: Regeneron Pharmaceuticals Inc. – Employee, Shareholder.

Renata Martincova: Sanofi – Employee, Stock Options.

Allen Radin: Regeneron Pharmaceuticals Inc. – Employee, Shareholder.

Lila Glotfelty: Sanofi – Employee, Stock Options.

David Binion, MD¹, Brian G. Feagan, MD², Eric Mortensen, MD, PhD³, Elizabeth Laws, PhD⁴, Jennifer Maloney, MD³, Renata Martincova, MD⁴, Allen Radin, MD³, Lila Glotfelty, MD, PhD⁴. P0198 - A Phase 2 Study Design to Investigate the Efficacy and Safety of Dupilumab Therapy Compared With Placebo in Adults With Moderately to Severely Active Ulcerative Colitis With an Eosinophilic Phenotype, ACG 2023 Annual Scientific Meeting Abstracts. Vancouver, BC, Canada: American College of Gastroenterology.