P3602 - Bowel Urgency and Abdominal Pain in Patients with Moderately to Severely Active Ulcerative Colitis in the Etrasimod ELEVATE UC Clinical Program: A Post Hoc Analysis

Tuesday, October 24, 2023

10:30 AM – 4:00 PM PT

Location: Exhibit Hall

Has Audio

Presenting Author(s)

Marla C. Dubinsky, MD

Mount Sinai Kravis Children’s Hospital
New York, NY

Marla C. Dubinsky, MD¹, María Chaparro, MD, PhD², Alessandro Armuzzi, MD, PhD³, Peter M.. Irving, MD⁴, Matthieu Allez, MD, PhD⁵, Remo Panaccione, MD⁶, Martina Goetsch, MD⁷, Lauren Bartolome, PharmD, MS⁸, Eustratios Bananis, PhD⁹, Joseph Wu, PhD¹⁰, Karolina Wosik, MSc, PhD¹¹, Abhishek Bhattacharjee, PhD¹², Christina C.. Smith, PharmD, MBA⁹, Bruce E. Sands, MD, MS, FACG¹³
¹Mount Sinai Kravis Children’s Hospital, New York, NY; ²Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS Princesa), Universidad Autónoma de Madrid (UAM), Centro de Investigacíon Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, Madrid, Spain; ³IRCCS Humanitas Research Hospital, Milan, Lombardia, Italy; ⁴Guy’s and St. Thomas’ NHS Foundation Trust, London, England, United Kingdom; ⁵Hôpital Saint Louis, Université Paris Cité, Paris, Ile-de-France, France; ⁶University of Calgary, Calgary, AB, Canada; ⁷Pfizer AG, Zurich, Zurich, Switzerland; ⁸Pfizer Inc., New York, NY; ⁹Pfizer Inc., Collegeville, PA; ¹⁰Pfizer Inc., Cambridge, MA; ¹¹Pfizer Canada, Kirkland, PQ, Canada; ¹²Pfizer Healthcare India Pvt. Ltd, Chennai, Tamil Nadu, India; ¹³Icahn School of Medicine at Mount Sinai, New York, NY

Introduction: Abdominal pain (AP) and bowel urgency (BU) are ulcerative colitis (UC) symptoms that result in quality of life impairment.¹Etrasimod is an investigational, oral, once-daily, selective sphingosine 1‑phosphate (S1P)_1,4,5 receptor modulator in development for the treatment of moderately to severely active UC. Efficacy was demonstrated in the ELEVATE UC clinical program.

Methods: The treatment effect of etrasimod vs placebo (PBO) on AP and BU was assessed as a post hoc analysis of the ELEVATE UC program. In ELEVATE UC 52 (NCT03945188) and ELEVATE UC 12 (NCT03996369), patients (pts) were randomized 2:1 to once‑daily etrasimod 2 mg or PBO. ELEVATE UC 52 had a treat-through design with a 12-week (wk) induction followed by a 40-wk maintenance period. ELEVATE UC 12 was a 12-wk induction study. In both trials, AP and BU data were assessed as pt-reported outcomes (PROs) at baseline (BL), Wks12 (both trials) and 52 (ELEVATE UC 52 only) using two 11-point numeric rating scales (NRS). The NRSs measured the worst AP and the severity of urgency to have a bowel movement in the past 24 hours and ranged from 0 (no pain or urgency) to 10 (pain as bad as can imagine or worst possible urgency). Endpoints included AP NRS=0, and, for pts with BL BU score ≥ 3: BU NRS clinically meaningful improvement (≥ 3 point decrease from BL) or remission (BU NRS ≤ 1).²

Results: At BL, the mean NRS scores ranged from 4.2 to 4.6 for AP and from 6.4 to 6.8 for BU across treatment arms and studies (Table). Significantly greater proportions of etrasimod- vs PBO-treated pts had no AP at Wk12 (ELEVATE UC 12: 33.2% vs 18.1%; ELEVATE UC 52: 27.7% vs 15.3%) and Wk52 (ELEVATE UC 52: 22.8% vs 10.4%) (all p< 0.01; Table). Similarly, significantly greater proportions of etrasimod- vs PBO-treated pts had no BU in both trials at Wk12 (18.1% vs 9.8%; 16.9% vs 6.7%, all p< 0.05), the difference did not meet statistical significance at Wk52 (ELEVATE UC 52: 17.3% vs 10.1%, p=0.0573; Table). In both trials, a significantly greater proportion of etrasimod- vs PBO-treated pts reported a BU NRS score of ≤ 1 and a decrease from BL of ≥ 3 points at Wk12 (both ELEVATE UC trials) and Wk52 (ELEVATE UC 52; all p< 0.05; Figure).

Discussion: Etrasimod improved AP and BU scores compared to PBO; a numerically greater proportion of etrasimod-treated pts reported no AP or no BU or had clinically meaningful decreases in BU at Wks12 and 52.

References

1. Hibi T et al. Inflamm Intest Dis 2020; 5: 27–35.

2. Dubinsky MC et al. J Patient Rep Outcomes 2022; 6: 114.

Figure: Figure. Proportions of Patients with (A) BU Remission (BU NRS of ≤ 1) and (B) a Clinically Meaningful Improvement (BU NRS ≥ 3 Point Decrease from BL) in BU Among Patients with a BL BU NRS Score ≥ 3 in ELEVATE UC 52 and ELEVATE UC 12.

Missing responses are considered as non-responses
Δ: adjusted difference in response rates for etrasimod vs PBO; BL, baseline; BU, bowel urgency; CI, confidence internal; PBO, placebo; n, number of responders; N2: number of patients with BL BU NRS score ≥ 3 points included in the analyses of BU NRS ≤ 1 and decrease from BL in BU NRS ≥ 3 points; NRS, numerical rating scale, QD, once daily; UC, ulcerative colitis; Wk, week.

	ELEVATE UC 52			ELEVATE UC 12
	PBO QD (N=144)	Etrasimod 2 mg QD (N=289)	Diff (95% CI) p value [a],[b]	PBO QD (N=116)	Etrasimod 2 mg QD (N=238)	Diff (95% CI) p value [a],[b]
Worst AP (NRS) in past 24 hr at BL, N1 Mean (SD)	131 4.4 (2.83)	272 4.6 (2.74)	NA	111 4.4 (2.75)	221 4.2 (2.74)	NA
AP NRS=0 Wk 12, n/N (%)	22/144 (15.3)	80/289 (27.7)	12.45 (4.64, 20.26) 0.0018	21/116 (18.1)	79/238 (33.2)	14.97 (5.81, 24.13) 0.0014
AP NRS=0 Wk 52, n/N (%)	15/144 (10.4)	66/289 (22.8)	12.27 (5.39, 19.15) 0.0005	NA	NA	NA
Severity of urgency (NRS) in past 24 hr at BL, N1 Mean (SD)	131 6.8 (2.61)	272 6.8 (2.43)	NA	111 6.4 (2.48)	221 6.4 (2.64)	NA
BU NRS=0 Wk 12, n/N2 (%)	8/119 (6.7)	43/255 (16.9)	10.50 (3.99, 17.02) 0.0016	10/102 (9.8)	36/199 (18.1)	8.18 (0.45, 15.9) 0.0380
BU NRS=0 Wk 52, n/N2 (%)	12/119 (10.1)	44/255 (17.3)	7.06 (-0.22, 14.34) 0.0573	NA	NA	NA
Missing responses are considered as non-responses; [a] Difference in response proportion (etrasimod vs PBO) is based on Cochran-Mantel-Haenszel method; [b] Two-sided nominal p values are reported without adjustment for multiple comparisons AP, abdominal pain; BL, baseline; BU, bowel urgency; CI, confidence interval; Diff, difference; FAS, full analysis set; hr, hours; MMS, modified Mayo score; n, number of responders; N, number of patients in the FAS; N1, number of patients with observations at baseline; N2: number of patients with BL BU NRS score ≥ 3 points included in the analysis of BU NRS=0; NA, not applicable; NRS, numerical rating scale; PBO, placebo; QD, once daily; SD, standard deviation; Wk, week

Disclosures:

Marla Dubinsky: AbbVie – Consultant, Grant/Research Support. Arena Pharmaceuticals – Consultant. Astra Zeneca – Consultant. Celgene – Consultant. Genentech Inc. – Consultant. Gilead Sciences – Consultant. Janssen – Consultant, Grant/Research Support. Merck – Consultant. Pfizer – Consultant, Grant/Research Support. Prometheus Biosciences – Consultant, Grant/Research Support. Prometheus Labs – Consultant, Grant/Research Support. Takeda – Consultant, Licensing fees. Thabor – Consultant. Trellus Health – Stock-publicly held company(excluding mutual/index funds). UCB Pharma – Consultant.

María Chaparro: Gilead – Consultant. Janssen – Consultant. Lilly – Consultant. Pfizer Inc – Consultant. Takeda – Consultant. Tillots – Consultant.

Alessandro Armuzzi: Abbvie – Consultant, Speakers Bureau. Arena – Consultant. Biogen – Grant/Research Support. Boehringer Ingelheim – Consultant. Bristol-Myers Squibb – Consultant, Speakers Bureau. Celltrion – Consultant. Eli Lilly – Consultant. Ferring Pharmaceuticals – Consultant. Galapagos – Consultant, Speakers Bureau. Gilead Sciences – Consultant, Speakers Bureau. Janssen – Consultant, Speakers Bureau. MSD – Consultant, Speakers Bureau. Novartis – Speakers Bureau. Pfizer inc – Grant/Research Support. Samsung Bioepis – Consultant, Speakers Bureau. Sandoz – Consultant, Speakers Bureau. Takeda – Consultant, Speakers Bureau.

Peter Irving: AbbVie – Advisory Committee/Board Member, lecture fees. Arena – Advisory Committee/Board Member. Boehringer-Ingelheim – Advisory Committee/Board Member. Bristol Myers Squibb – Advisory Committee/Board Member, lecture fees. Celgene – Advisory Committee/Board Member, lecture fees. Celltrion – Advisory Committee/Board Member, Grant/Research Support, lecture fees. Eli Lilly – Advisory Committee/Board Member, lecture fees. Falk Pharma – lecture fees. Ferring – lecture fees. Galapagos – Grant/Research Support, lecture fees. Genetech – Advisory Committee/Board Member. Gilead – Advisory Committee/Board Member, lecture fees. Hospira – Advisory Committee/Board Member. Janssen – Advisory Committee/Board Member, lecture fees. MSD – Advisory Committee/Board Member, Grant/Research Support, lecture fees. Pfizer – Advisory Committee/Board Member, Grant/Research Support, lecture fees. Pharmacosmos – Advisory Committee/Board Member. Prometheus – Advisory Committee/Board Member. Roche – Advisory Committee/Board Member. Samsung Bioepis – Advisory Committee/Board Member. Sandoz – Advisory Committee/Board Member, lecture fees. Sapphire Medical – lecture fees. Shire – lecture fees. Takeda – Advisory Committee/Board Member, Grant/Research Support, lecture fees. Tillots – lecture fees. Topivert – Advisory Committee/Board Member. VH2 – Advisory Committee/Board Member. Vifor Pharma – Advisory Committee/Board Member. Warner Chilcott – Advisory Committee/Board Member, lecture fees.

Matthieu Allez: Abbvie – Consultant, Speakers Bureau. Amgen – Consultant. Biogen – Consultant. Boehringer Ingelheim – Consultant. Bristol-Myers Squibb/Celgene – Consultant. Celltrion – Consultant. Celsius – Consultant. Egle Therapeutics – Consultant. Endpoint Health – Consultant. Ferring – Consultant. Galapagos – Consultant, Speakers Bureau. Genentech – Consultant, Grant/Research Support, Speakers Bureau. IQVIA – Consultant. Janssen – Consultant, Grant/Research Support, Speakers Bureau. Lilly – Consultant. Novartis – Consultant. Pfizer Inc – Consultant, Speakers Bureau. Roche – Consultant, Grant/Research Support, Speakers Bureau. Takeda – Consultant, Grant/Research Support, Speakers Bureau. Tillotts – Consultant, Speakers Bureau.

Remo Panaccione: Abbivax – Consultant. Abbott – Consultant. AbbVie – Consultant. Alimentiv – Consultant. Amgen – Consultant. Arena – Consultant. AstraZeneca – Consultant. Biogen – Consultant. Boehringer Ingelheim – Consultant. Bristol Myers Squibb – Consultant. Celgene – Consultant. Celltrion – Consultant. Cosmos Technology – Consultant. Eisai – Consultant. Elan – Consultant. Eli Lilly – Consultant. Ferring – Consultant. Fresenius Kabi – Consultant. Galapagos – Consultant. Genentech – Consultant. Gilead Sciences – Consultant. GlaxoSmithKline – Consultant. JAMP Bio – Consultant. Janssen – Consultant. Merck – Consultant. Mylan – Consultant. Novartis – Consultant. Oppilan Pharma – Consultant. Organon – Consultant. Pandion Pharma – Consultant. Pendopharm – Consultant. Pfizer Inc – Consultant. Progenity – Consultant. Prometheus – Consultant. Protagonist Therapeutics – Consultant. Roche – Consultant. Sandoz – Consultant. Satisfai Health – Consultant. Shire – Consultant. Sublimity Therapeutics – Consultant. Takeda Pharmaceuticals – Consultant. Theravance Biopharma – Consultant. Trellus – Consultant. UCB – Consultant. Ventyx – Consultant. Viatris – Consultant.

Martina Goetsch: Pfizer AG – Employee. Pfizer Inc – Stock-publicly held company(excluding mutual/index funds).

Lauren Bartolome: Pfizer Inc – Employee, Stock Options.

Eustratios Bananis: Pfizer Inc – Employee, Stock-publicly held company(excluding mutual/index funds).

Joseph Wu: Pfizer Inc – Employee, Stock Options.

Karolina Wosik: Pfizer Canada – Employee, Stock-publicly held company(excluding mutual/index funds).

Abhishek Bhattacharjee: Pfizer Healthcare India – Employee. Pfizer Inc – Stock Options.

Christina Smith: Pfizer Inc – Employee, Stock-publicly held company(excluding mutual/index funds).

Bruce Sands: AbbVie – Consultant. Abivax – Consultant, Speaker’s fees. Adiso Therapeutics – Consultant. Alimentiv – Consultant. Amgen – Consultant. Arena pharmaceuticals – Consultant. Artizan Biosciences – Consultant. Artugen Therapeutics – Consultant. AstraZeneca – Consultant. Bacainn Therapeutics – Consultant. Biora Therapeutics – Consultant. Boehringer Ingelheim – Consultant. Boston Pharmaceuticals – Consultant. Bristol Myers Squibb – Consultant, Grant/Research Support, speaking fees and other support. Calibr – Consultant. Celltrion – Consultant. ClostraBio – Consultant. Connect Biopharm – Consultant. Cytoki Pharma – Consultant. Eli Lilly – Consultant, speaking fees and other support. Enthera – Consultant. Evommune – Consultant. Ferring – Consultant. Fresenius Kabi – Consultant. Galapagos – Consultant. Genentech – Consultant. Gilead Sciences – Consultant. GlaxoSmithKline – Consultant. Gossamer Bio – Consultant. HMP Acquisition – Consultant. Imhotex – Consultant. Immunic – Consultant. InDex Pharmaceuticals – Consultant. Innovation Therapeutics – Consultant. Inotrem – Consultant. Ironwood Pharmaceuticals – Consultant. Janssen – Grant/Research Support, consulting and speaking fees and other support. Johnson & Johnson – Consultant. Kaleido Biosciences – Consultant. Kallyope – Consultant. Merck – Consultant. MiroBio – Consultant. Morphic Therapeutics – Consultant. MRM Health – Consultant. OSE Immunotherapeutics – Consultant. Pfizer Inc – Consultant, Grant/Research Support, speaking fees and other support. Progenity – Consultant. Prometheus Biosciences – Consultant. Prometheus Laboratories – Consultant. Protagonist Therapeutics – Consultant. Q32 Bio – Consultant. RedHill Biopharma – Consultant. Sun Pharma – Consultant. Surrozen – Consultant. Synlogic Operating Company – Consultant. Takeda – Grant/Research Support, consulting and speaking fees and other support. Target RWE – Consultant. Theravance Biopharma – Consultant, Grant/Research Support. TLL Pharmaceutical – Consultant. USWM Enterprises – Consultant. Ventyx Biosciences – Consultant, personal fees and stock options for consulting. Viela Bio – Consultant.