P0699 - Etrasimod Demonstrated Consistent Efficacy and Safety as a Monotherapy or With Concomitant Use of Corticosteroids and/or 5‑Aminosalicylates: Results From the ELEVATE UC Clinical Program

Sunday, October 22, 2023

3:30 PM – 7:00 PM PT

Location: Exhibit Hall

Presenting Author(s)

Andres J. Yarur, MD

Associate Professor of Medicine
Inflammatory Bowel Disease Center, Cedars-Sinai Medical Center
Los Angeles, CA

Andres J.. Yarur, MD¹, Michael V.. Chiorean, MD², Jessica R.. Allegretti, MD, MPH³, Raymond K.. Cross, MD, MS, FACG⁴, Christina Ha, MD⁵, Martina Goetsch, MD⁶, Christopher J.. Rabbat, PhD⁷, Aoibhinn McDonnell, PhD⁸, Joseph Wu, PhD⁹, Naja Fragante, RN, MPH¹⁰, Arcangelo M.. Abbatemarco, MD¹¹, Julian Panés, MD, PhD¹²
¹Inflammatory Bowel Disease Center, Cedars-Sinai Medical Center, Los Angeles, CA; ²Inflammatory Bowel Disease Center, Swedish Medical Center, Seattle, WA; ³Brigham and Women's Hospital, Harvard Medical School, Boston, MA; ⁴University of Maryland School of Medicine, Baltimore, MD; ⁵Mayo Clinic Arizona, Scottsdale, AZ; ⁶Pfizer AG, Zurich, Zurich, Switzerland; ⁷Pfizer Inc., New York, NY; ⁸Pfizer Ltd., Sandwich, England, United Kingdom; ⁹Pfizer Inc., Cambridge, MA; ¹⁰Pfizer Inc., Manila, National Capital Region, Philippines; ¹¹Pfizer Inc., Peapack, NJ; ¹²Hospital Clínic de Barcelona, IDIBAPS, CIBERehd, Barcelona, Catalonia, Spain

Introduction: Etrasimod 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 ulcerative colitis (UC). In the phase 3 ELEVATE UC clinical program, background concomitant oral corticosteroid (CS, prednisone [≤ 20 mg/day], budesonide [≤ 9 mg/day], or equivalent) and/or oral 5-aminosalicylates (5-ASA) use for UC at baseline was allowed, if patients (pts) were on a stable dose (≥ 2 weeks [wks] prior to randomization for 5-ASA and 4 wks prior to the screening endoscopy assessment for CS use) and maintained this throughout for 5-ASA use and through Wk12 for CS use, after which CS tapering was recommended but not mandated, per protocol.

Methods: We assessed etrasimod efficacy and safety as a monotherapy or with concomitant CS and/or 5-ASA use at baseline. In ELEVATE UC 52 (NCT03945188) and ELEVATE UC 12 (NCT03996369), pts aged 16–80 years with moderately to severely active UC (baseline modified Mayo score 4–9) and a history of inadequate response, loss of response or intolerance to ≥ 1 approved UC treatment were randomized 2:1 to etrasimod 2 mg once daily or placebo (PBO). Predefined clinical endpoints were assessed at Wk12 (pooled from both trials) and/or 52 (ELEVATE UC 52 only). Safety was assessed up to Wk52.

Results: Of 787 randomized pts (etrasimod: N=527; PBO: N=260), 107 (13.6%) had no concomitant UC therapy use, 51 (6.5%) had concomitant CS use only, 447 (56.8%) had concomitant 5-ASA use only, and 182 (23.1%) had concomitant CS and 5-ASA use. In all subgroups, higher proportions of etrasimod-treated pts achieved all efficacy endpoints at Wks12 and 52 vs PBO (Figure). Differences vs PBO were statistically significant for all endpoints at Wks12 and 52 in pts without concomitant UC therapy or with concomitant 5-ASA use only, and for clinical remission, CS-free clinical remission, and endoscopic improvement at Wk52 in pts with concomitant CS use only (Figure). Safety was consistent regardless of concomitant UC therapy, with etrasimod-treated pts having similar infection (including opportunistic infections and herpes zoster) and serious infection rates vs PBO (Table).

Discussion: In the ELEVATE UC clinical program, etrasimod efficacy and safety were consistent across subgroups, regardless of concomitant CS and/or 5-ASA use, suggesting that etrasimod monotherapy is a viable treatment option in select pts with UC. Data interpretability may be limited by the small sample size in some subgroups.

Figure: Figure. Achievement of (A) Clinical Remission, (B) Endoscopic Improvement, and (C) CS-Free Clinical Remission in Pts with UC Stratified by Concomitant UC Therapy (Full Analysis Set)

	No concomitant UC therapy (N=107)		Concomitant CS use only (N=51)		Concomitant 5-ASA use only (N=447)		Concomitant CS and 5-ASA use (N=182)
	PBO (N1=42)	Etrasimod 2 mg (N1=65)	PBO (N1=15)	Etrasimod 2 mg (N1=36)	PBO (N1=142)	Etrasimod 2 mg (N1=305)	PBO (N1=61)	Etrasimod 2 mg (N1=121)
Most common TEAEs [a], n (%) [IR, per 100 PY]
Headache	2 (4.8) [13.1]	10 (15.4) [31.9]	1 (6.7) [18.6]	1 (2.8) [5.8]	6 (4.2) [11.0]	14 (4.6) [9.3]	0	10 (8.3) [16.5]
Colitis ulcerative	3 (7.1) [19.5]	5 (7.7) [14.1]	3 (20.0) [64.2]	2 (5.6) [11.7]	4 (2.8) [7.2]	15 (4.9) [9.7]	4 (6.6) [14.3]	9 (7.4) [13.9]
Pyrexia	4 (9.5) [26.2]	6 (9.2) [17.0]	2 (13.3) [39.0]	0	3 (2.1) [5.4]	13 (4.3) [8.6]	0	3 (2.5) [4.6]
Nausea	0	5 (7.7) [14.3]	1 (6.7) [20.3]	1 (2.8) [5.9]	2 (1.4) [3.6]	11 (3.6) [7.2]	1 (1.6) [3.5]	2 (1.7) [3.1]
Dizziness	0	4 (6.2) [11.6]	0	1 (2.8) [6.1]	1 (0.7) [1.8]	10 (3.3) [6.5]	0	3 (2.5) [4.7]
Arthralgia	1 (2.4) [6.4]	1 (1.5) [2.8]	1 (6.7) [21.6]	1 (2.8) [6.0]	4 (2.8) [7.3]	10 (3.3) [6.5]	0	5 (4.1) [7.7]
Urinary tract infection	0	5 (7.7) [14.3]	1 (6.7) [19.7]	1 (2.8) [5.8]	1 (0.7) [1.8]	4 (1.3) [2.6]	1 (1.6) [3.6]	0
Diarrhea	1 (2.4) [6.5]	2 (3.1) [5.5]	0	2 (5.6) [11.6]	0	3 (1.0) [1.9]	0	1 (0.8) [1.5]
Fatigue	0	3 (4.6) [8.4]	1 (6.7) [19.4]	1 (2.8) [5.8]	1 (0.7) [1.8]	1 (0.3) [0.6]	0	3 (2.5) [4.7]
Hypertension	0	2 (3.1) [5.6]	0	0	1 (0.7) [1.8]	5 (1.6) [3.2]	1 (1.6) [3.5]	4 (3.3) [6.3]
Summary of TEAEs, n (%) [IR, per 100 PY]
Serious AEs	2 (4.8) [13.0]	4 (6.2) [11.2]	2 (13.3) [37.2]	2 (5.6) [11.9]	1 (0.7) [1.8]	15 (4.9) [9.9]	6 (9.8) [21.8]	5 (4.1) [7.7]
Serious infections	1 (2.4) [6.4]	0	1 (6.7) [18.5]	0	1 (0.7) [1.8]	3 (1.0) [1.9]	2 (3.3) [7.2]	0
AEs leading to discontinuation	2 (4.8) [12.9]	5 (7.7) [13.7]	2 (13.3) [37.2]	1 (2.8) [5.8]	3 (2.1) [5.4]	14 (4.6) [9.0]	1 (1.6) [3.5]	5 (4.1) [7.6]
AEs of special interest [b]
Macular edema	0	0	0	0	0	0	0	1 (0.8) [1.5]
Cardiovascular events	0	3 (4.6) [8.4]	0	2 (5.6) [12.3]	2 (1.4) [3.6]	9 (3.0) [5.8]	0	6 (5.0) [9.4]
AV conduction delay	0	1 (1.5) [2.7]	0	1 (2.8) [6.1]	0	1 (0.3) [0.6]	0	0
Bradycardia	0	0	0	0	0	2 (0.7) [1.3]	0	2 (1.7) [3.0]
Hypertension	0	2 (3.1) [5.6]	0	1 (2.8) [5.8]	2 (1.4) [3.6]	6 (2.0) [3.9]	0	4 (3.3) [6.3]
Infections (all)	1 (2.4) [6.4]	1 (1.5) [2.7]	1 (6.7) [18.5]	0	4 (2.8) [7.3]	6 (2.0) [3.9]	3 (4.9) [10.8]	3 (2.5) [4.6]
Opportunistic infections (narrow) [c]	0	0	0	0	1 (0.7) [1.8]	1 (0.3) [0.6]	0	0
Herpes zoster	0	1 (1.5) [2.7]	0	0	1 (0.7) [1.8]	0	1 (1.6) [3.5]	1 (0.8) [1.5]
[a] Most common TEAEs shown are among the five most common TEAEs occurring in etrasimod-treated pts, per subgroup; [b] AEs are SDEI and met the review criteria; [c] Opportunistic infections is based on the Standardized Medical Dictionary for Regulatory Activities query (version 24.1), narrow definition For AEs with 0 pts with events, % and IR are also 0, so not displayed. Percentages are based on the number of pts in each subgroup as the denominator. IRs were calculated as n/PY adjusted to per 100 PY. PY is defined as the sum of the pt time from baseline to first AE episode or time in the study if the pt was event-free 5-ASA, 5-aminosalicylates; AE, adverse event; AV, atrioventricular; CS, corticosteroid; IR, incidence rate; N, number of pts in the analysis set by concomitant UC therapy subgroup; N1, number of pts by treatment group in each concomitant UC therapy subgroup; n, number of pts with each specific outcome; PBO, placebo; pt; patient; PY, pt-years; SDEI, sponsor‑designated events of interest; TEAE, treatment-emergent adverse event; UC, ulcerative colitis

Table: Table. Summary of Safety in Pts with UC Stratified by Concomitant UC Therapy

Disclosures:

Andres Yarur: Arena – Consultant. Bristol-Myers Squibb – Consultant, Speakers Bureau. Pfizer – Consultant. Takeda – Consultant.

Michael Chiorean: AbbVie – Consultant, Speakers Bureau. Bristol Myers Squibb – Consultant, Speakers Bureau. Eli Lilly – Consultant. Fresenius Kabi – Consultant, Speakers Bureau. Fuji – Grant/Research Support. Gilead – Grant/Research Support. Janssen – Consultant, Grant/Research Support, Speakers Bureau. Novartis – Grant/Research Support. Pfizer – Consultant, Grant/Research Support, Speakers Bureau. Takeda – Consultant, Grant/Research Support, Speakers Bureau.

Jessica Allegretti: Abbvie – Consultant, Speakers Bureau. Adiso Therapeutics – Consultant. Artizan – Consultant. Artugen Therapeutics – Consultant. Baccain – Consultant. Bristol-Myers Squibb/Celgene – Consultant, Speakers Bureau. Ferring Pharmaceuticals – Consultant. Finch Therapeutics – Consultant. Iterative Scopes – Consultant. Janssen – Consultant, Grant/Research Support, Speakers Bureau. Merck – Consultant, Grant/Research Support. Morphic – Consultant. Pandion Therapeutics – Consultant. Pfizer – Consultant, Grant/Research Support. Roivant Sciences – Consultant. Seres Therapeutics – Consultant. Servatus – Consultant. Summit – Consultant.

Raymond Cross: AbbVie – Consultant. Bristol Myers Squibb – Consultant. Janssen – Consultant. LabCorp – Consultant. Pfizer – Consultant. Samsung Bioepis – Consultant. Takeda – Consultant.

Christina Ha: AbbVie – Advisory Committee/Board Member, Consultant, Grant/Research Support. Bristol-Myers Squibb – Advisory Committee/Board Member, Consultant. Helmsley Charitable Trust, – Grant/Research Support. Janssen – Advisory Committee/Board Member, Consultant. Lily – Advisory Committee/Board Member, Consultant. Pfizer Inc – Advisory Committee/Board Member, Consultant, Grant/Research Support. Roivant – Advisory Committee/Board Member, Consultant. Takeda – Advisory Committee/Board Member, Consultant.

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

Christopher Rabbat: Pfizer Inc – Employee, Stock Options.

Aoibhinn McDonnell: Pfizer Ltd – Employee, Stock Options.

Joseph Wu: Pfizer Inc – Employee, Stock Options.

Naja Fragante: Pfizer Inc – Employee.

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

Julian Panés: AbbVie – Grant/Research Support, Personal fees. Arena – Consultant. Athos – Consultant. Atomwise – Consultant. Boehringer Ingelheim – Consultant. Celgene – Consultant. Celltrion – Consultant. Ferring – Consultant, Speakers Bureau. Galapagos – Consultant. Genentech/Roche – Consultant. GlaxoSmithKline – Consultant. Immunic – Personal fees. Janssen – Consultant, payment for development of educational presentations. Mirum – Consultant. Morphic – Consultant. Origo – Consultant. Pandion – Consultant. Pfizer Inc – Grant/Research Support, payment for development of educational presentations. Progenity – Consultant. Revolo – Consultant. Takeda – payment for development of educational presentations. Theravance – Consultant. Wasserman – Consultant.