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Sunday Poster Session

Category: IBD

P0728 - Impact of Etrasimod on Blood Pressure and Hypertension: Data From the Etrasimod Ulcerative Colitis Clinical Program

Sunday, October 22, 2023
3:30 PM – 7:00 PM PT
Location: Exhibit Hall
Séverine Vermeire, MD, PhD1, David T. Rubin, MD2, Laurent Peyrin-Biroulet, MD, PhD3, Marla C. Dubinsky, MD4, Miguel Regueiro, MD5, Peter M.. Irving, MD6, Martina Goetsch, MD7, Krisztina Lazin, MD7, Joseph Wu, PhD8, Irene Modesto, MD, PhD9, John C.. Woolcott, PhD10, Aoibhinn McDonnell, PhD11, Christopher J.. Rabbat, PhD9, Andres J.. Yarur, MD12
1UZ Leuven, Leuven, Vlaams-Brabant, Belgium; 2Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, IL; 3Last Inserm U954 and CHU de Nancy, Lorraine University, Vandoeuvre-lès-Nancy, Lorraine, France; 4Mount Sinai Kravis Children’s Hospital, New York, NY; 5Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, OH; 6Guy’s and St. Thomas’ NHS Foundation Trust, London, England, United Kingdom; 7Pfizer AG, Zurich, Zurich, Switzerland; 8Pfizer Inc., Cambridge, MA; 9Pfizer Inc., New York, NY; 10Pfizer Inc., Collegeville, PA; 11Pfizer Ltd., Sandwich, England, United Kingdom; 12Inflammatory Bowel Disease Center, Cedars-Sinai Medical Center, Los Angeles, CA

Introduction: Increased blood pressure (BP) and hypertension are known adverse effects of sphingosine 1-phosphate (S1P)1,4,5 receptor modulators. Etrasimod is an investigational, oral, once-daily, selective S1P1,4,5 receptor modulator in development for the treatment of moderately to severely active ulcerative colitis (UC).

Methods: We assessed the impact of etrasimod on BP and hypertension development among patients (pts) in the etrasimod UC clinical program. Pivotal (placebo [PBO]-controlled phase [p]3 [NCT03945188; NCT03996369] studies) and All UC (PBO-controlled plus open-label extension [OLE]; p2 [NCT02447302], p3, and OLE [NCT03950232 and NCT04176588, data snapshot January 31, 2022; NCT02536404] studies) cohort data were analyzed. BP was assessed at each visit and at 2 and 4 weeks (wks) post‑treatment cessation. Proportions and exposure-adjusted incidence rates (EAIRs; pts with AEs divided by the total pt‑years [PY] at risk for AEs, per 1 PY) of treatment‑emergent hypertension (Medical Dictionary for Regulatory Activities preferred term [PT]) AEs among pts receiving etrasimod (2 mg once daily; both cohorts) or PBO (Pivotal UC cohort) were assessed. Characteristics of pts with hypertension AEs that met sponsor-designated events of interest (SDEI) criteria (related to hypertension associated with sustained increases in BP [systolic/diastolic: ≥ 160/100 mmHg], or requiring new or increased antihypertensive therapy) were analyzed descriptively.

Results: In the Pivotal and All UC cohorts, 11/527 (2.1%; EAIR, 0.04; PBO: 2/260 [0.8%; EAIR, 0.02]) and 20/942 (2.1%; EAIR, 0.03) etrasimod-treated pts had PT hypertension, respectively; none led to study treatment discontinuation. In the All UC cohort, 19/942 (2.0%; EAIR, 0.02) etrasimod-treated pts had hypertension-related SDEIs. Of these events, 6 were in pts with hypertension history; none were serious or led to treatment discontinuation; 6 resolved (5 with intervention), 8 were resolving/unknown outcome and 3 were unresolved. Etrasimod‑treated pts had minimal changes in BP over time (All UC cohort, mean change in systolic/diastolic BP at Wk52: 2.9/1.2 mmHg, respectively; Table). In the All UC cohort, at Wk104, no etrasimod-treated pts had a systolic/diastolic BP > 160/100 mmHg, respectively.

Discussion: Hypertension events were infrequent among etrasimod-treated pts. No clinically meaningful changes in BP with etrasimod 2 mg over time or following treatment discontinuation were observed up to 2 years. Data interpretations are limited by small pt numbers.
Time pointPivotal UC cohortTime pointAll UC cohort
Systolic BP, mmHgDiastolic BP, mmHgSystolic BP, mmHgDiastolic BP, mmHg
Etrasimod
2 mg QD
(N=527)		PBO
(N=260)		Etrasimod
2 mg QD
(N=527)		PBO
(N=260)		Etrasimod 2 mg QD
(N=942)
Baseline [a], mean (SD)
[etrasimod, n=527;
PBO, n=260]		120.7 (12.50)121.3 (13.08)75.8 (8.53)77.2 (9.56)Baseline [a],
mean (SD)
[n=942]		119.6 (12.89)75.6 (8.57)
Change at Wk12, mean (SD)
[etrasimod, n=474;
PBO, n=231]		2.0 (11.17)-1.4 (10.68)1.6 (8.08)-0.4 (8.07)Change at Wk12,
mean (SD)
[n=821]		2.1 (10.78)1.7 (8.01)
Change at Wk52, mean (SD)
[etrasimod, n=162; PBO, n=44]		2.2 (11.08)1.3 (9.16)0.4 (8.47)-0.8 (8.52)Change at Wk52,
mean (SD)
[n=246]		2.9 (10.39)1.2 (8.36)
Change at Wk78/ Wk104 [b], mean (SD)
[N/A]		----Change at Wk78/ Wk104, mean (SD)
[Wk78, n=147;
Wk104, n=29]		1.9 (10.65)/
-0.7 (13.54)		1.1 (8.05)/
0.8 (7.40)
Change at 2-/4-wk follow-up visit [c], mean (SD)
[2 wk: etrasimod, n=39;
PBO, n=6; 4 wk: etrasimod, n=36; PBO, n=10]		0.2 (10.66)/
-0.4 (11.47)		6.7 (10.61)/
8.1 (8.18)		1.6 (7.99)/
0.2 (10.40)		3.2 (3.71)/
3.0 (7.12)		Change at 2-/4-wk follow-up visit [c],
mean (SD)
[2‑wk; n=203;
4‑wk, n=105]		2.6 (13.73)/
1.9 (12.43)		1.3 (8.74)/
1.4 (9.18)
Pivotal UC cohort comprised pts from the PBO-controlled p3 ELEVATE UC 52 (NCT03945188) and p3 ELEVATE UC 12 (NCT03996369) studies. All UC cohort comprised pts from the p2 OASIS (NCT02447302), p2 OASIS OLE (NCT02536404 [completed November 01, 2018]), p3 ELEVATE UC 52 (NCT03945188), p3 ELEVATE UC 12 (NCT03996369), and p3 ELEVATE UC OLE (NCT03950232 [data snapshot January 31, 2022]) studies, and the open-label phase of the p3 study NCT04176588 (data snapshot January 31, 2022)

[a] Baseline is defined, by study treatment group received, as the last non-missing measurement taken on or prior to the study treatment group start date; [b] Wk78 and 104 data are not provided for the Pivotal UC cohort as only data up to Wk52 of ELEVATE UC 52 are included for pts in this cohort; [c] Pts who did not participate in the OLE study had 2-wk and 4-wk follow-up visits after their last treatment administration

BP, blood pressure; N, total number of patients; n, number of patients with evaluable data at a visit; N/A, not applicable; OLE, open-label extension; p, phase; PBO, placebo; pts, patients; QD, once daily; SD, standard deviation; UC, ulcerative colitis; wk, week

Table: Table. Change from Baseline in BP Over Time Among Pts in the Etrasimod UC Clinical Program (Pivotal and All UC Cohorts).


Disclosures:
Séverine Vermeire: AbbVie – Consultant, Grant/Research Support. AbolerIS Pharma – Grant/Research Support. AgomAb – Grant/Research Support. Alimentiv – Consultant. Arena Pharmaceuticals – Consultant. AstraZeneca – Consultant. Avaxia Biologics – Consultant. Boehringer Ingelheim – Consultant. Bristol Myers Squibb – Consultant. Celgene – Consultant. CVasThera – Consultant, Speakers Bureau. Cytoki Pharma – Consultant, Speakers Bureau. Dr. Falk Pharma – Consultant, Speakers Bureau. Eli Lilly – Consultant, Speakers Bureau. Ferring Pharmaceuticals – Consultant, Speakers Bureau. Galapagos – Consultant, Grant/Research Support, Speakers Bureau. Genentech/Roche – Consultant, Speakers Bureau. Gilead – Consultant, Speakers Bureau. GSK – Consultant, Speakers Bureau. Hospira – Consultant, Speakers Bureau. IMIDomics – Consultant, Speakers Bureau. Janssen Pharmaceuticals – Consultant, Speakers Bureau. Johnson & Johnson – Consultant, Grant/Research Support, Speakers Bureau. Materia Prima – Consultant, Speakers Bureau. MiroBio – Consultant, Speakers Bureau. Morphic – Consultant, Speakers Bureau. MRM Health – Consultant, Speakers Bureau. MSD – Consultant, Speakers Bureau. Mundipharma – Consultant, Speakers Bureau. Pfizer – Consultant, Grant/Research Support, Speakers Bureau. ProDigest – Consultant, Speakers Bureau. Progenity – Consultant, Speakers Bureau. Prometheus – Consultant, Speakers Bureau. Robarts Clinical Trials – Consultant, Speakers Bureau. Second Genome – Consultant, Speakers Bureau. Shire – Consultant, Speakers Bureau. Surrozen – Consultant, Speakers Bureau. Takeda – Consultant, Grant/Research Support, Speakers Bureau. Theravance Biopharma – Consultant, Speakers Bureau. Tillotts Pharma – Consultant, Speakers Bureau. Zealand Pharma – Consultant, Speakers Bureau.
David Rubin: AbbVie – Consultant, personal fees. AltruBio – Consultant, personal fees. Aslan Pharmaceuticals – Consultant. Athos Therapeutics – Consultant. Bellatrix Pharmaceuticals – Consultant. Boehringer Ingelheim – Consultant, personal fees. Bristol Myers Squibb – Consultant. Celgene Chronicles – Consultant. ClostraBio – Consultant. Connect BioPharma – Consultant. Corp/Syneos – Consultant. Eco R1 – Consultant. GastroIntestinal Research Foundation – Grant/Research Support. Genentech/Roche – Consultant. Gilead Sciences – Consultant, personal fees. Helmsley Charitable Trust – Grant/Research Support. Iterative Health – Consultant. Janssen Pharmaceuticals – Consultant, personal fees. Kaleido Biosciences – Consultant. Lilly – Consultant. Pfizer – Consultant, personal fees. Prometheus Biosciences – Consultant. Reistone Biopharma – Consultant, personal fees. Seres Therapeutics – Consultant. Takeda – Consultant, Grant/Research Support, Personal fees. Target RWE – Consultant. Trellus Health – Consultant.
Laurent Peyrin-Biroulet: AbbVie – Advisory Committee/Board Member, Consultant, Grant/Research Support, Speakers Bureau. Allergan – personal fees. Alma – personal fees. Amgen – Advisory Committee/Board Member, Consultant, Speakers Bureau. Applied Molecular Transport – personal fees. Arena – personal fees. Biogaran – Advisory Committee/Board Member, Consultant, Speakers Bureau. Biogen – Advisory Committee/Board Member, Consultant, Speakers Bureau. Boehringer Ingelheim – Advisory Committee/Board Member, Consultant, Speakers Bureau. Bristol Myers Squibb – personal fees. Celgene – Advisory Committee/Board Member, Consultant, Speakers Bureau. Celltrion – Advisory Committee/Board Member, Consultant, Speakers Bureau. CTMA – Stock Options. Eli Lilly – Advisory Committee/Board Member, Consultant, Speakers Bureau. Enterome – personal fees. Enthera – personal fees. Ferring – Advisory Committee/Board Member, Consultant, Speakers Bureau. Forward Pharma – Advisory Committee/Board Member, Consultant, Speakers Bureau. Fresenius – personal fees. Genentech – Advisory Committee/Board Member, Consultant, Speakers Bureau. Gilead – personal fees. H.A.C. Pharma – Advisory Committee/Board Member, Consultant, Speakers Bureau. Hikma – personal fees. Hospira/Pfizer – Advisory Committee/Board Member, Consultant, Speakers Bureau. Index Pharmaceuticals – Advisory Committee/Board Member, Consultant, Speakers Bureau. Janssen – Advisory Committee/Board Member, Consultant, Speakers Bureau. Lycera – Advisory Committee/Board Member, Consultant, Speakers Bureau. Merck – Advisory Committee/Board Member, Consultant, Speakers Bureau. Mitsubishi – Advisory Committee/Board Member, Consultant, Speakers Bureau. MSD – Grant/Research Support, personal fees. Mylan – personal fees. Nestlé – personal fees. Norgine – Advisory Committee/Board Member, Consultant, Speakers Bureau. Oppilan Pharma – personal fees. OSE Immunotherapeutics – personal fees. Pfizer – personal fees. Pharmacosmos – personal fees. Roche – personal fees. Samsung Bioepis – Advisory Committee/Board Member, Consultant, Speakers Bureau. Sandoz – Advisory Committee/Board Member, Consultant, Speakers Bureau. Sterna – personal fees. Sublimity Therapeutics – personal fees. Takeda – Advisory Committee/Board Member, Consultant, Speakers Bureau. Theravance – Advisory Committee/Board Member, Consultant, Speakers Bureau. Tillots – Advisory Committee/Board Member, Consultant, Speakers Bureau. Vifor – Advisory Committee/Board Member, Consultant, Speakers Bureau.
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.
Miguel Regueiro: AbbVie – Advisory Committee/Board Member, Consultant, Unrestricted educational grants. Alfasigma – Advisory Committee/Board Member, Consultant. Allergan – Advisory Committee/Board Member, Consultant. Amgen – Advisory Committee/Board Member, Consultant. Bristol Myers Squibb – Advisory Committee/Board Member, Consultant, Unrestricted educational grants. Celgene – Advisory Committee/Board Member, Consultant, Unrestricted educational grants. Eli Lilly – Advisory Committee/Board Member, Consultant. Genentech – Advisory Committee/Board Member, Consultant, Unrestricted educational grants. Gilead Sciences – Advisory Committee/Board Member, Consultant, Unrestricted educational grants. Janssen – Advisory Committee/Board Member, Consultant, Unrestricted educational grants. Miraca Labs – Advisory Committee/Board Member, Consultant. Pfizer Inc – Advisory Committee/Board Member, Consultant, Unrestricted educational grants. Prometheus – Advisory Committee/Board Member, Consultant. Salix – Advisory Committee/Board Member, Consultant. Seres – Advisory Committee/Board Member, Consultant. Takeda – Advisory Committee/Board Member, Consultant, Unrestricted educational grants. Target RWE – Advisory Committee/Board Member, Consultant. UCB – Advisory Committee/Board Member, Consultant, Unrestricted educational grants. Wolters Kluwer Health – Royalties.
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.
Martina Goetsch: Pfizer AG – Employee. Pfizer Inc – Stock-publicly held company(excluding mutual/index funds).
Krisztina Lazin: Pfizer AG – Employee, Stock Options.
Joseph Wu: Pfizer Inc – Employee, Stock Options.
Irene Modesto: Pfizer Inc – Employee, Stock Options.
John Woolcott: Pfizer Inc – Employee, Stock Options.
Aoibhinn McDonnell: Pfizer Ltd – Employee, Stock Options.
Christopher Rabbat: Pfizer Inc – Employee, Stock Options.
Andres Yarur: Arena – Consultant. Bristol-Myers Squibb – Consultant, Speakers Bureau. Pfizer – Consultant. Takeda – Consultant.


Séverine Vermeire, MD, PhD1, David T. Rubin, MD2, Laurent Peyrin-Biroulet, MD, PhD3, Marla C. Dubinsky, MD4, Miguel Regueiro, MD5, Peter M.. Irving, MD6, Martina Goetsch, MD7, Krisztina Lazin, MD7, Joseph Wu, PhD8, Irene Modesto, MD, PhD9, John C.. Woolcott, PhD10, Aoibhinn McDonnell, PhD11, Christopher J.. Rabbat, PhD9, Andres J.. Yarur, MD12. P0728 - Impact of Etrasimod on Blood Pressure and Hypertension: Data From the Etrasimod Ulcerative Colitis Clinical Program, ACG 2023 Annual Scientific Meeting Abstracts. Vancouver, BC, Canada: American College of Gastroenterology.