D0406 - Efficacy and Safety of 2 Years of Continuous Ozanimod Treatment: Interim Analysis of the True North Open-Label Extension Study

Tuesday, October 25, 2022

10:00 AM – 12:00 PM ET

Location: Crown Ballroom

Has Audio

Presenting Author(s)

MA

Maria T. Abreu, MD

The University of Miami Health System
Miami, FL

Maria T. Abreu, MD¹, Parambir Dulai, MD², Axel Dignass, MD, PhD³, Edoardo Savarino, MD, PhD⁴, David Hudesman, MD⁵, Anita Afzali, ⁶, Vipul Jairath, MBChB, DPhil⁷, Mark Osterman, MD, PhD⁸, Lucy Akukwe, PharmD, MS⁸, W. Jerry Liu, MS⁸, Arteid Memaj, MBA⁸, AnnKatrin Petersen, MD, MS⁸, Anjali Jain, PhD⁸, James B. Canavan, BA, MB, BCh, BAO⁸, Séverine Vermeire, MD, PhD⁹
¹The University of Miami Health System, Miami, FL; ²Feinberg School of Medicine, Northwestern University, Chicago, IL; ³Agaplesion Markus Hospital / Goethe University, Frankfurt, Hessen, Germany; ⁴University of Padua, Padua, Veneto, Italy; ⁵NYU Langone Health, New York, NY; ⁶University of Cincinnati, Cincinnati, OH; ⁷Western University, London, ON, Canada; ⁸Bristol Myers Squibb, Princeton, NJ; ⁹University Hospitals Leuven, Leuven, Brussels Hoofdstedelijk Gewest, Belgium

Introduction: The phase 3 True North (TN) study demonstrated the efficacy and safety of oral ozanimod (OZA) 0.92 mg once daily (equivalent to OZA HCl 1 mg) in patients (pts) with moderately to severely active ulcerative colitis (UC). The ongoing TN open-label extension (OLE) study is exploring longer-term efficacy and safety of OZA in UC. This interim analysis of the TN OLE evaluated the efficacy and safety of OZA in pts who received 98 weeks of continuous OZA treatment.

Methods: Pts in clinical response (CRS) after 52 weeks of continuous OZA during TN who rolled over into the OLE were included (data cutoff: September 30, 2020). Nearly 73% of pts had completed OLE Week 46 (Week 98 of continuous OZA therapy) at the time of data cutoff when outcomes were measured. Endoscopy was performed annually throughout the OLE and was scored by Mayo endoscopic score. Efficacy data (Clinical Remission [CRM], CRS, Endoscopic Improvement [EI], and Corticosteroid-Free Remission [CFR]) were analyzed using observed cases (OC) and nonresponder imputation (NRI). Safety data were also recorded.

Results: Of 131 total pts in CRS at TN Week 52, 83 (63%) were in CRM and 48 (37%) were in CRS only (but not CRM) on entry to the OLE. Demographic and clinical characteristics at TN baseline were similar for pts in both subgroups, except that a higher proportion of pts with only CRS at OLE entry were exposed to prior immunomodulators or tumor necrosis factor inhibitors at TN baseline. A high proportion of the overall population sustained CRM, CRS, EI, and CFR on OZA at OLE Week 46 in both OC and NRI analyses, with higher rates of CRM, EI, and CFR among pts entering the OLE in CRM (Table). Notably, 97% of all pts sustained CRS through overall Week 98 in OC analysis (64% in NRI analysis). Of the pts in CRS only at OLE entry, 55% achieved CRM by OLE Week 46 in OC analysis (NRI: 32%). Mean partial Mayo score over time for the overall population is shown in the Figure. No new safety findings emerged from this extended analysis; 1 sudden death occurred during the OLE and was adjudicated to be unrelated to OZA.

Discussion: This interim analysis of the TN OLE found that pts who achieved CRS or CRM after 1 year of OZA had a high rate of sustaining CRS, CRM, and EI for another year. Pts who after a year of OZA were in CRS could achieve CRM with continued OZA therapy. No additional safety signals were observed.

Figure: Figure. Mean partial Mayo scores of OZA over time in the overall population of pts in CRS at TN Week 52

Clinical endpoints at OLE Week 46, % (n/N)	Overall population at TN Week 52 (n=131)		Pt subgroup in CRM^a at TN Week 52 (n=83)		Pt subgroup in CRS^b only at TN Week 52 (n=48)
Clinical endpoints at OLE Week 46, % (n/N)	OC^c	NRI^d	OC^c	NRI^d	OC^c	NRI^d
Clinical Remission	67 (42/63)	44 (42/95)	73 (30/41)	53 (30/57)	55 (12/22)	32 (12/38)
Clinical Response	97 (61/63)	64 (61/95)	98 (40/41)	70 (40/57)	95 (21/22)	55 (21/38)
Endoscopic Improvement^e	74 (55/74)	58 (55/95)	82 (41/50)	72 (41/57)	58 (14/24)	37 (14/38)
Corticosteroid-Free Remission^f	63 (40/63)	42 (40/95)	71 (29/41)	51 (29/57)	50 (11/22)	29 (11/38)
^aCRM was defined as RBS = 0 and SFS ≤1 point (and a decrease of ≥1 point from the baseline SFS) and mucosal endoscopy subscore ≤1 without friability. ^bCRS was defined as reduction of 3-component Mayo score of ≥2 points and at least 35%, and reduction in RBS of ≤1 point or an absolute RBS of ≤1. ^cDenominators for OC were based on the number of pts who completed Week 46. ^dDenominators for NRI were based on the number of pts who completed Week 46 of the OLE and those who withdrew before Week 46 but would have reached Week 46 if they had stayed. This did not include the number of pts in the OLE who have not yet completed Week 46 or who discontinued and would not have reached Week 46 by this data cutoff. ^eEndoscopy subscore of ≤1 point. ^fClinical remission while off corticosteroids for ≥12 weeks. CRM, clinical remission; CRS, clinical response; CRS only, clinical response but not remission; RBS, rectal bleeding subscore; SFS, stool frequency subscore.

Table: Table. OZA efficacy at OLE Week 46 (overall Week 98) in pts entering OLE in CRS (OC and NRI data)

Disclosures:

Maria Abreu: AbbVie – Advisory Committee/Board Member, Consultant. Alimentiv – Speakers Bureau. Arena Pharmaceuticals – Advisory Committee/Board Member, Consultant. Bristol Myers Squibb – Advisory Committee/Board Member, Consultant. Eli Lilly – Advisory Committee/Board Member, Consultant. Gilead – Advisory Committee/Board Member, Consultant. Intellisphere (HCP Live Institutional Perspectives in GI) – Speakers Bureau. Janssen – Speakers Bureau. Janssen Biotech (nonbranded) – Consultant. Janssen Biotech (Women in GI Advisory Board) – Advisory Committee/Board Member, Consultant. Janssen Biotech NART – Consultant. Janssen Global Services – Consultant. Janssen Ortho – Advisory Committee/Board Member, Consultant. Microba – Advisory Committee/Board Member, Consultant. Pfizer – Grant/Research Support. Prime CME – Speakers Bureau. Prometheus Biosciences – Advisory Committee/Board Member, Consultant, Grant/Research Support. Takeda – Grant/Research Support, Speakers Bureau. UCB Biopharma – Advisory Committee/Board Member, Consultant. WebMD Global – Advisory Committee/Board Member, Consultant.

Parambir Dulai: Bristol Myers Squibb – Consultant. Digbi Health – Stock-publicly held company(excluding mutual/index funds). Eli Lilly – Consultant. Gilead – Consultant. Janssen – Consultant. Novartis – Consultant. Pfizer – Consultant, Grant/Research Support. PreciDiag – Royalties, Stock-publicly held company(excluding mutual/index funds). Takeda – Consultant, Grant/Research Support.

Axel Dignass: AbbVie – Consultant, Speakers Bureau. Abivax – Consultant. Amgen – Consultant. Biogen – Consultant. Boehringer Ingelheim – Consultant. Celgene/Bristol Myers Squibb – Consultant. Eli Lilly – Consultant, Speakers Bureau. Falk Foundation – Consultant, Speakers Bureau. Ferring – Consultant, Speakers Bureau. Fresenius Kabi – Consultant. Galapagos – Consultant, Speakers Bureau. Gilead – Consultant, Speakers Bureau. Janssen – Consultant, Speakers Bureau. MSD – Consultant, Speakers Bureau. Pfizer – Consultant, Speakers Bureau. Pharmacosmos – Consultant. Roche/Genentech – Consultant. Sandoz/Hexal – Consultant. Takeda – Consultant, Speakers Bureau. Tillotts – Consultant, Speakers Bureau. Vifor – Consultant, Speakers Bureau.

Edoardo Savarino: AbbVie – Speakers Bureau. AG Pharma – Speakers Bureau. Alfasigma – Consultant, Speakers Bureau. Amgen – Consultant. Biogen – Consultant. Bristol Myers Squibb – Consultant. Celltrion – Consultant. Diadema Farmaceutici – Consultant. EG Stada Group – Speakers Bureau. Falk – Consultant. Fresenius Kabi – Consultant, Speakers Bureau. Grifols – Speakers Bureau. Innovamedica – Speakers Bureau. Janssen – Consultant, Speakers Bureau. Malesci – Speakers Bureau. Merck – Consultant. Pfizer – Speakers Bureau. Reckitt Benckiser – Consultant, Grant/Research Support, Speakers Bureau. Regeneron – Consultant. Sandoz – Speakers Bureau. Sanofi – Consultant. Shire – Consultant. SILA – Consultant, Grant/Research Support, Speakers Bureau. Sofar – Consultant, Grant/Research Support, Speakers Bureau. Synformulas GmbH – Consultant. Takeda – Consultant, Speakers Bureau. Unifarco – Consultant, Grant/Research Support, Speakers Bureau.

David Hudesman: Abbvie – Consultant. Bristol Myers Squibb – Consultant. Janssen – Consultant, Grant/Research Support. Pfizer – Consultant, Grant/Research Support. Takeda – Consultant.

Anita Afzali: AbbVie – Consultant, Speakers Bureau. Bristol Myers Squibb – Consultant, Speakers Bureau. DiaSorin – Consultant. Eli Lilly – Consultant. Gilead – Consultant. Janssen – Consultant, Speakers Bureau. Pfizer – Consultant, Speakers Bureau. Takeda – Consultant, Speakers Bureau. TLL Pharmaceuticals – Consultant.

Vipul Jairath: AbbVie – consulting/advisory board fees, speaker’s fees. Alimentiv Inc – Consulting/advisory board fees. Arena pharmaceuticals – consulting/advisory board fees. Asahi Kasei Pharma – Consulting/advisory board fees. Asieris – consulting/advisory board fees. AstraZeneca – consulting/advisory board fees. Bristol Myers Squibb – consulting/advisory board fees, speaker’s fees. Celltrion – consulting/advisory board fees. Eli Lilly and Company – consulting/advisory board fees. Ferring – consulting/advisory board fees, speaker's fees. Flagship Pioneering – consulting/advisory board fees. Fresenius Kabi – consulting/advisory board fees, speaker’s fees. Galapagos – consulting/advisory board fees, speaker’s fees. Genentech – consulting/advisory board fees. Gilead – consulting/advisory board fees. GlaxoSmithKline – consulting/advisory board fees. Janssen – consulting/advisory board fees, speaker’s fees. Merck – consulting/advisory board fees. Metacrine – consulting/advisory board fees. Mylan – consulting/advisory board fees. Pandion – consulting/advisory board fees. Pendopharm – consulting/advisory board fees. Pfizer – consulting/advisory board fees, speaker’s fees. Prometheus – consulting/advisory board fees. Protagonist Therapeutics – consulting/advisory board fees. Reistone Biopharma – consulting/advisory board fees. Roche – consulting/advisory board fees. Sandoz – consulting/advisory board fees. Second Genome – consulting/advisory board fees. Shire – speaker’s fees. Sorriso pharmaceuticals – consulting/advisory board fees. Takeda – consulting/advisory board fees, speaker’s fees. Teva – consulting/advisory board fees. Topivert – consulting/advisory board fees. Ventyx Biosciences – consulting/advisory board fees. Vividion Therapeutics – consulting/advisory board fees.

Mark Osterman: Bristol Myers Squibb – Employee, Stock-publicly held company(excluding mutual/index funds).

Lucy Akukwe: Bristol Myers Squibb – Employee, Stock-publicly held company(excluding mutual/index funds).

W. Jerry Liu: Bristol Myers Squibb – Employee, Stock-publicly held company(excluding mutual/index funds).

Arteid Memaj: Bristol Myers Squibb – Employee, Stock-publicly held company(excluding mutual/index funds).

AnnKatrin Petersen: Bristol Myers Squibb – Employee, Stock-publicly held company(excluding mutual/index funds).

Anjali Jain: Bristol Myers Squibb – Employee, Stock-publicly held company(excluding mutual/index funds).

James Canavan: Bristol Myers Squibb – Employee, Stock-publicly held company(excluding mutual/index funds).

Séverine Vermeire: AbbVie – Consultant, Grant/Research Support. Arena – Consultant. Celgene – Consultant. Eli Lilly – Consultant. Ferring – Consultant. Galapagos – Consultant. Genentech/Roche – Consultant. Gilead – Consultant. Hospira – Consultant. Janssen – Consultant. Johnson & Johnson – Grant/Research Support. MSD – Consultant. Mundipharma – Consultant. Pfizer – Consultant, Grant/Research Support. Progenity – Consultant. Second Genome – Consultant. Shire – Consultant. Takeda – Consultant, Grant/Research Support.