A0391 - Evaluation of Ozanimod Efficacy and Safety in Older Patients With Ulcerative Colitis: Post Hoc Analysis From the Phase 3 True North Study

Sunday, October 23, 2022

5:00 PM – 7:00 PM ET

Location: Crown Ballroom

Presenting Author(s)

NK

Nabeel Khan, MD

Corporal Michael J. Crescenz VA Medical Center
Philadelphia, Pennsylvania

Nabeel Khan, MD¹, Peter Irving, MD, MA², Irina Blumenstein, MD³, Sara N. Horst, MD⁴, Harris A. Ahmad, MD⁵, Garrett Lawlor, MD⁵, Vanessa Hobbs, MBA, RN⁵, Anjali Jain, PhD⁵, Arteid Memaj, MBA⁵, Ashwin N. Ananthakrishnan, MBBS, MPH⁶
¹Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA; ²Guy’s and St. Thomas’ NHS Foundation Trust, London, England, United Kingdom; ³Goethe University Hospital, Frankfurt, Hessen, Germany; ⁴Vanderbilt University Medical Center, Nashville, TN; ⁵Bristol Myers Squibb, Princeton, NJ; ⁶Massachusetts General Hospital & Harvard Medical School, Boston, MA

Introduction: Ozanimod (OZA), an oral S1P receptor modulator, is approved for the treatment (tx) of moderate/severe ulcerative colitis (UC) in the US and EU. Inflammatory bowel disease prevalence is increasing in older pts.

Methods: This post hoc analysis examined OZA efficacy and safety in pts < 60y and ≥60y in True North (TN). Pts were randomized to double-blind (DB) OZA 0.92 mg or placebo (PBO; Cohort 1 [C1]) or received open-label OZA (Cohort 2 [C2]) during the 10-week (W) TN induction period (IP). Pts with clinical response to OZA at W10 were rerandomized to DB OZA or PBO in the maintenance period (MP) through W52.

Results: This analysis included 562 pts < 60y (OZA, n=376; PBO, n=186) and 83 pts ≥60y (OZA, n=53; PBO, n=30) from C1 and 315 pts (< 60y) and 52 pts (≥60y) from C2. During MP, 196 pts (< 60y) and 34 pts (≥60y) continued on OZA; 196 pts (< 60y) and 31 pts (≥60y) were rerandomized to PBO. Demographics and baseline (BL) characteristics were generally well balanced across tx and age groups; older pts had less extensive disease, lower BL fecal calprotectin levels, and more polypharmacy. Adjusted tx differences favored OZA v PBO and were generally similar between age groups across all efficacy endpoints (clinical remission, clinical response, endoscopic improvement, mucosal healing) at W10 and W52. PBO response rates were higher in older v younger pts. During IP, tx-emergent adverse event (TEAE) incidence with OZA in C1 and C2 was lower in older pts; rates of serious TEAEs and TEAEs leading to tx discontinuation were similar in older v younger pts (Table). With continued OZA tx during MP, TEAEs occurred more often in older pts, serious TEAEs were less frequent in older pts, and TEAEs leading to tx discontinuation were similar in older v younger pts. Adverse events of special interest during MP were generally low overall, with the most common being infection (≥60y: 2 pts v < 60y: 3 pts), hepatic effects (≥60y: 0 pts v < 60y: 2 pts), macular edema (≥60y: 1pt v < 60y: 0 pts), malignancy (≥60y: 0 pts v < 60y: 2 pts), and pulmonary effects (≥60y: 0 pts v < 60y: 1 pt). One death from acute respiratory distress syndrome due to viral pneumonia occurred during IP in an older pt (64y) on OZA but was deemed unrelated to tx.

Discussion: OZA is a safe, tolerable, oral tx option for older UC pts with an absence of serious AEs of concern. OZA efficacy in older pts was comparable to younger pts. This study was limited by the small sample size, warranting larger future real-world studies.

Table. TEAEs in older and younger pts on OZA in TN
TEAE, n (%)	< 60 y			≥60 y
TEAE, n (%)	IP C1: OZA (n=376)	IP C2: OZA (n=315)	MP: OZA-OZA (n=196)	IP C1: OZA (n=53)	IP C2: OZA (n=52)	MP: OZA-OZA (n=34)
≥1 TEAE	153 (41%)	130 (41%)	94 (48%)	19 (36%)	16 (31%)	19 (56%)
≥1 serious TEAE	14 (4%)	21 (7%)	11 (6%)	3 (6%)	2 (4%)	1 (3%)
≥1 TEAE leading to tx discontinuation	13 (3.5%)	11 (3.5%)	2 (1%)	1 (2%)	3 (6%)	1 (3%)

Disclosures:

Nabeel Khan: Pfizer – Grant/Research Support. Pharmacosmos – Advisory Committee/Board Member. Samsung – Grant/Research Support. Takeda – Advisory Committee/Board Member, Grant/Research Support.

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

Irina Blumenstein: AbbVie – Consultant, Speakers Bureau. Amgen – Consultant, Speakers Bureau. Arena – Consultant, Speakers Bureau. Biogen – Consultant, Speakers Bureau. Bristol Myers Squibb – Consultant, Speakers Bureau. Celgene – Speakers Bureau. Celltrion – Consultant, Speakers Bureau. Ferring – Consultant, Speakers Bureau. Galapagos – Consultant, Speakers Bureau. Janssen – Consultant, Speakers Bureau. Mylan – Speakers Bureau. Pfizer – Consultant, Speakers Bureau. Shire – Consultant, Speakers Bureau. Takeda – Consultant, Speakers Bureau.

Sara Horst: Abbvie – Consultant. Janssen – Consultant. Takeda – Consultant.

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

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

Vanessa Hobbs: 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).

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

Ashwin N. Ananthakrishnan: Iterative Scopes – Advisory Committee/Board Member. Menten AI – Advisory Committee/Board Member.

Nabeel Khan, MD¹, Peter Irving, MD, MA², Irina Blumenstein, MD³, Sara N. Horst, MD⁴, Harris A. Ahmad, MD⁵, Garrett Lawlor, MD⁵, Vanessa Hobbs, MBA, RN⁵, Anjali Jain, PhD⁵, Arteid Memaj, MBA⁵, Ashwin N. Ananthakrishnan, MBBS, MPH⁶. A0391 - Evaluation of Ozanimod Efficacy and Safety in Older Patients With Ulcerative Colitis: Post Hoc Analysis From the Phase 3 True North Study, ACG 2022 Annual Scientific Meeting Abstracts. Charlotte, NC: American College of Gastroenterology.