P0756 - Durability of Symptomatic and Clinical Outcomes in Ozanimod-Treated Patients by Endpoints of Increasing Objectivity at True North Week 52: Interim Analysis of the True North Open-Label Extension Study

Sunday, October 22, 2023

3:30 PM – 7:00 PM PT

Location: Exhibit Hall

Has Audio

Presenting Author(s)

DM

Dimpy Mehra, PharmD

Bristol Myers Squibb
Princeton, New Jersey

Maria T. Abreu, MD¹, Remo Panaccione, MD², Séverine Vermeire, MD, PhD³, David T. Rubin, MD⁴, Dimpy Mehra, PharmD⁵, Hsiuanlin Wu, MS⁵, Mark T. Osterman, MD, PhD⁵, Harris A. Ahmad, MD⁵, Anjali Jain, PhD⁵, Silvio Danese, MD, PhD⁶
¹University of Miami Miller School of Medicine, Miami, FL; ²University of Calgary, Calgary, AB, Canada; ³UZ Leuven, Leuven, Vlaams-Brabant, Belgium; ⁴Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, IL; ⁵Bristol Myers Squibb, Princeton, NJ; ⁶IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Lombardia, Italy

Introduction: Ozanimod (OZA) is approved for the treatment (tx) of moderately to severely active ulcerative colitis per results of the phase 3 True North (TN) study. Data from the ongoing open-label extension (OLE) demonstrated durability of efficacy in symptomatic, clinical, and mucosal endpoints up to 3 y with continuous OZA tx in patients (pts) who were clinical responders at TN Week (W) 52.

Methods: This interim analysis of the TN OLE (cutoff: 10Jan2022) explored whether achieving endpoints at TN W52, examined by increasing objectivity, would impact the durability of symptomatic and clinical outcomes with continuous OZA tx up to OLE W94. OZA clinical responders at TN W52 who continued in the OLE were included in this analysis (N=131). These pts were categorized into subgroups based on achieved endpoints of increasing objectivity (ie, clinical response [CRes], clinical remission [CRem], endoscopic improvement, complete endoscopic healing [endoscopy score=0], histologic remission, mucosal healing, and stringent mucosal healing) at TN W52 to determine whether these endpoints at TN W52/OLE baseline influence the proportion of pts maintaining symptomatic (ie, total/partial Mayo scores and symptomatic CRes) and clinical (ie, CRes, CRem, or corticosteroid [CS]–free remission) outcomes in the OLE. OLE outcomes were assessed up to OLE W94 using observed case (OC) and nonresponder imputation (NRI) analyses.

Results: Of 131 pts in this analysis, 114 (87%) completed OLE W46 and 94 (72%) completed OLE W94. OC analyses showed that partial and total Mayo scores and symptomatic CRes were similar and sustained over 94 wk of continuous OZA tx during the OLE, regardless of endpoint achieved at TN W52. Likewise, maintenance of CRes at OLE W46 and OLE W94 was not impacted by the achievement of endpoints of increasing objectivity at TN W52 (Table). Achievement of CRem at TN W52 had an incremental benefit over CRes at TN W52 for the maintenance of CRem and CS-free remission at OLE W94, but other endpoints of higher objectivity had no additional benefit (Table). A similar pattern was observed for NRI analyses. Clinical outcomes were sustained from OLE W46 to OLE W94 regardless of endpoint achieved at TN W52: CRes: 71.4%–78.4%; CRem: 65.2%–70.0%; and CS-free remission: 63.6%–70.6%.

Discussion: Symptomatic response and clinical outcomes with OZA were durable up to OLE W94. Maintenance of these long-term outcomes was not notably impacted by the achievement of increasingly more objective measures of responsiveness at TN W52.

Endpoint, % (n/N)	CRes^a		CRem^b		CS-free remission^c
Endpoint, % (n/N)	OLE W46	OLE W94	OLE W46	OLE W94	OLE W46	OLE W94
CRes^a (N=131)	95.9 (93/97)	91.4 (74/81)	72.2 (70/97)	69.1 (56/81)	70.1 (68/97)	67.9 (55/81)
CRem^b (N=83)	97.0 (64/66)	94.4 (51/54)	81.8 (54/66)	75.9 (41/54)	80.3 (53/66)	74.1 (40/54)
Endoscopic improvement (MES ≤1; N=93)	97.3 (73/75)	95.2 (60/63)	78.7 (59/75)	73.0 (46/63)	77.3 (58/75)	71.4 (45/63)
Complete endoscopic healing (MES=0; N=50)	97.6 (40/41)	90.9 (30/33)	82.9 (34/41)	69.7 (23/33)	80.5 (33/41)	66.7 (22/33)
Histologic remission (Geboes index score < 2.0; N=68)	98.1 (51/52)	95.3 (41/43)	82.7 (43/52)	74.4 (32/43)	80.8 (42/52)	72.1 (31/43)
Mucosal healing (MES ≤1 and Geboes index score < 2.0; N=61)	97.9 (46/47)	94.7 (36/38)	80.9 (38/47)	71.1 (27/38)	78.7 (37/47)	68.4 (26/38)
Stringent mucosal healing (MES=0 and Geboes index score < 2.0; N=37)	96.6 (28/29)	91.3 (21/23)	79.3 (23/29)	65.2 (15/23)	75.9 (22/29)	60.9 (14/23)

Table. Endpoints (increasing in objectivity) at TN W52 (OC analysis).

Denominators for the OC analysis were based on the numbers of pts who completed OLE W46 or OLE W94 and had data available for the endpoints in question.

aClinical response: reduction from baseline in the 9-point Mayo score of ≥2 points and ≥35%, and a reduction from baseline in RBS of ≥1 point or an absolute RBS of ≤1 point. bClinical remission: RBS=0, SFS ≤1 point (and a decrease of ≥1 point from the baseline SFS), and endoscopy subscore ≤1 point. cCS-free remission: Clinical remission while off CS for ≥12 wk.

MES, mucosal endoscopy subscore; RBS, rectal bleeding subscore; SFS, stool frequency subscore.

Disclosures:

Maria T. Abreu: AbbVie – Advisory Committee/Board Member, Consultant. Alimentiv – Speakers Bureau. Amgen – Advisory Committee/Board Member, Consultant, Speakers Bureau. Arena – Advisory Committee/Board Member, Consultant. Bristol Myers Squibb – Advisory Committee/Board Member, Consultant. Celsius Therapeutics – Advisory Committee/Board Member, Consultant. Eli Lilly – Advisory Committee/Board Member, Consultant. Gilead Sciences – Advisory Committee/Board Member, Consultant. Janssen – Advisory Committee/Board Member, Consultant, Speakers Bureau. Microba Life Sciences, – Advisory Committee/Board Member, Consultant. Pfizer – Advisory Committee/Board Member, Consultant. Prometheus Biosciences – Advisory Committee/Board Member, Consultant. Takeda – Speakers Bureau. UCB Biopharma – Advisory Committee/Board Member, Consultant. WebMD Global – Advisory Committee/Board Member, Consultant.

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.

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.

Dimpy Mehra: Bristol Myers Squibb – employee and/or shareholder.

Hsiuanlin Wu: Bristol Myers Squibb – employee and/or shareholder.

Mark T. Osterman: Bristol Myers Squibb – employee and/or shareholder.

Harris A. Ahmad: Bristol Myers Squibb – employee and/or shareholder.

Anjali Jain: Bristol Myers Squibb – employee and/or shareholder.

Silvio Danese: AbbVie – Consultant, personal fees (lecture fees). Alimentiv – Consultant. Allergan – Consultant, personal fees. Amgen – Consultant, lecture fees. Applied Molecular Transport – Consultant. AstraZeneca – Consultant, personal fees. Athos Therapeutics – Consultant, personal fees. Biogen – Consultant, personal fees. Boehringer Ingelheim – Consultant, personal fees. Bristol Myers Squibb – Consultant. Celgene – Consultant, personal fees. Celltrion Healthcare – Consultant, Personal fees. Dr Falk Pharma – Consultant. Eli Lilly – Consultant, personal fees. Enthera – Consultant, personal fees. Ferring Pharmaceuticals – Consultant, lecture fees. Gilead – Consultant, lecture fees. Hospira – Consultant, personal fees. Inotrem – Consultant, personal fees. Janssen Pharmaceuticals – Consultant, lecture fees. Johnson & Johnson – Consultant, personal fees. Morphic – Consultant. MSD – Consultant, personal fees. Mundipharma – Consultant, personal fees. Mylan – Consultant, lecture fees. Pfizer – Consultant, lecture fees. Roche – Consultant, personal fees. Sandoz – Consultant, personal fees. Sublimity Therapeutics – Consultant, personal fees. Takeda – Consultant, lecture fees. Teladoc Health – Consultant. TiGenix – Consultant, personal fees. UCB – Consultant, personal fees. Vial – Consultant. Vifor – Consultant, personal fees.

Maria T. Abreu, MD¹, Remo Panaccione, MD², Séverine Vermeire, MD, PhD³, David T. Rubin, MD⁴, Dimpy Mehra, PharmD⁵, Hsiuanlin Wu, MS⁵, Mark T. Osterman, MD, PhD⁵, Harris A. Ahmad, MD⁵, Anjali Jain, PhD⁵, Silvio Danese, MD, PhD⁶. P0756 - Durability of Symptomatic and Clinical Outcomes in Ozanimod-Treated Patients by Endpoints of Increasing Objectivity at True North Week 52: Interim Analysis of the True North Open-Label Extension Study, ACG 2023 Annual Scientific Meeting Abstracts. Vancouver, BC, Canada: American College of Gastroenterology.