P1637 - Long-term Safety of Ozanimod in Patients with Moderately to Severely Active Ulcerative Colitis (UC) and Relapsing Multiple Sclerosis (RMS) Studies

Monday, October 25, 2021

10:30 AM – 4:15 PM PT

Location: Shoreline Exhibit Hall

Has Audio

Presenting Author(s)

David T. Rubin, MD, FACG

University of Chicago Medicine, Inflammatory Bowel Disease Center
Chicago, IL, United States

David T. Rubin, MD, FACG¹, Douglas C. Wolf, MD², Olga Alekseeva, PhD³, Lorna Charles, MD⁴, Sonia Afsari, MD⁴, AnnKatrin Petersen, MD, MS⁵, James Sheffield, MD⁴, Hongjuan Li, MS⁴, Diego Silva, MD, PhD⁴, Fred D. Lublin, MD⁶, Bruce Cree, MD⁷, Jeffrey Cohen, MD⁸, Silvio Danese, MD, PhD⁹
¹University of Chicago Medicine, Inflammatory Bowel Disease Center, Chicago, IL; ²Center for Crohn’s Disease & Ulcerative Colitis, Atlanta Gastroenterology Associates, Atlanta, GA; ³Nizhni Novgorod Regional Clinical Hospital, Nizhny Novgorod, Nizhegorod, Russia; ⁴Bristol Myers Squibb, Princeton, NJ; ⁵Bristol Myers Squibb, Princeton, CA; ⁶Icahn School of Medicine at Mount Sinai, New York, NY; ⁷UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA; ⁸Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland, OH; ⁹Inflammatory Bowel Diseases Center, Humanitas Clinical and Research Center IRCCS and Hunimed, Milan, Lombardia, Italy

Introduction: Ozanimod, an oral sphingosine 1-phosphate (S1P) receptor modulator, is approved in the US for the treatment of adults with moderately to severely active UC, and in adults with relapsing forms of multiple sclerosis (MS) and in the EU and other countries for the treatment of adults with relapsing-remitting MS. Here we report the safety of extended exposure to ozanimod HCl 1 mg/day from the UC and relapsing MS (RMS) clinical trials.

Methods: Safety data were pooled from patients who received ozanimod 1 mg/day from all controlled and uncontrolled UC studies, including phase 2 and 3, and an ongoing, open-label extension (OLE) trial. As of September 30, 2020, safety data were available for 1158 UC patients with a mean ozanimod exposure of 22 months and a total of 2196.4 person-years (PY) exposure. RMS data were examined from DAYBREAK, an ongoing OLE trial that enrolled patients from 4 randomized phase 1, 2, or 3 parent trials; as of December 20, 2019, OLE data were available for 2494 RMS patients on ozanimod 1 mg/day for a mean of 35 months and a total exposure of 7161.0 PY.

Results: Treatment-emergent adverse events (TEAEs) occurred in 70.8% and 81.8% of patients in the UC and RMS populations, respectively. Severe TEAEs occurred in 10.2% and 6.1%, and serious TEAEs in 14.0% and 9.5% of patients with UC and RMS, respectively. TEAEs led to treatment discontinuation in 8.0% of patients in the UC studies and 2.2% of patients in the RMS study.

The most frequently reported TEAEs in the UC studies were lymphopenia (10.3%), nasopharyngitis (7.5%), and anemia (7.9%); exposure-adjusted incidence rates (IRs) per 100 PY were 5.84, 4.20, and 4.39, respectively. The most frequently reported TEAEs in the RMS study were nasopharyngitis (17.9%), headache (14.0%), upper respiratory tract infection (9.9%), and lymphopenia (9.6%); exposure-adjusted IRs per 100 PY were 6.99, 5.30, 3.67, and 3.61, respectively. IRs for infections (any) were 21.48 and 26.49, and IRs for serious infections were 1.29 and 0.72 in the UC and RMS datasets, respectively. IRs per 100 PY for TEAEs of special interest (herpes zoster, bradycardia, and macular edema) were low (Table). Increased alanine aminotransferase to >5x the upper limit of normal occurred in 2.1% of UC patients and 0.7% of MS patients.

Discussion: Long-term exposure to ozanimod 1 mg/day in patients with moderately to severely active UC and in patients with RMS was manageable, with low rates of safety events related to S1P modulators.

	UC Studies Ozanimod 1 mg (N=1158) Total PY = 2196.4		RMS Study Ozanimod 1 mg (N=2494) Total PY = 7161.0
	N (%)	Incidence Rate per 100 PY	N (%)	Incidence Rate per 100 PY
Herpes zoster	28 (2.4)	1.3	29 (1.2)^a	0.41
Bradycardia	7 (0.6)	0.69	1 (< 0.1)	0.07
Macular edema	7 (0.6)	0.32	8 (0.3)^b	0.11
PY, person-years. ^aIn addition, varicella zoster virus infection was reported in 3 patients (0.1%; IR per 100 PY=0.04) in the RMS studies. ^bOnly 3 cases were confirmed to have macular edema by a panel of specialists (Macular Edema Review Panel) in the RMS study.

Table: TEAEs of special interest (based on prior associations with S1P receptor modulation)

Disclosures:

David Rubin: AbbVie – Consultant. Celgene – Consultant. Janssen – Consultant. Pfizer – Consultant. Takeda – Consultant, Grant/Research Support.

Douglas Wolf: AbbVie – Advisory Committee/Board Member, Consultant, Speaker's Bureau. Arena – Advisory Committee/Board Member, Consultant, Speaker's Bureau. Celgene/Bristol Myers Squibb – Advisory Committee/Board Member, Consultant, Speaker's Bureau. Janssen – Advisory Committee/Board Member, Consultant, Speaker's Bureau. Pfizer – Advisory Committee/Board Member, Consultant, Speaker's Bureau. Prometheus – Advisory Committee/Board Member, Consultant, Speaker's Bureau. Takeda – Advisory Committee/Board Member, Consultant, Speaker's Bureau. UCB – Advisory Committee/Board Member, Consultant, Speaker's Bureau.

Olga Alekseeva: Janssen – Speaker's Bureau. Pfizer – Speaker's Bureau. Takeda – Speaker's Bureau.

Lorna Charles: Bristol Myers Squibb – Employee, Stockholder/Ownership Interest (excluding diversified mutual funds).

Sonia Afsari: Bristol Myers Squibb – Employee, Stockholder/Ownership Interest (excluding diversified mutual funds).

AnnKatrin Petersen: Bristol Myers Squibb – Employee, Stockholder/Ownership Interest (excluding diversified mutual funds).

James Sheffield: Bristol Myers Squibb – Employee, Stockholder/Ownership Interest (excluding diversified mutual funds).

Hongjuan Li: Bristol Myers Squibb – Employee, Stockholder/Ownership Interest (excluding diversified mutual funds).

Diego Silva: Bristol Myers Squibb – Employee, Stockholder/Ownership Interest (excluding diversified mutual funds).

Fred Lublin: Acetlion/Janssen – Advisory Committee/Board Member, Consultant, Other Financial or Material Support, data and safety monitoring board member. Acorda – Advisory Committee/Board Member, Consultant, Other Financial or Material Support, data and safety monitoring board member. Actelion – Grant/Research Support. Apitope – Advisory Committee/Board Member, Consultant, Other Financial or Material Support, data and safety monitoring board member. Atara Biotherapeutics – Advisory Committee/Board Member, Consultant, Other Financial or Material Support, data and safety monitoring board member. Avotres – Advisory Committee/Board Member, Consultant, Stockholder/Ownership Interest (excluding diversified mutual funds), Other Financial or Material Support, data and safety monitoring board member. Banner Life Sciences – Advisory Committee/Board Member, Consultant, Other Financial or Material Support, data and safety monitoring board member. Biogen – Advisory Committee/Board Member, Consultant, Grant/Research Support, Other Financial or Material Support, data and safety monitoring board member. Brainstorm Cell Therapeutics – Advisory Committee/Board Member, Consultant, Grant/Research Support, Other Financial or Material Support, data and safety monitoring board member. Bristol-Myers Squibb – Advisory Committee/Board Member. EMD Serono – Advisory Committee/Board Member, Consultant, Other Financial or Material Support, data and safety monitoring board member. EMD Serono (non-promotional) – Speaker's Bureau. GW Pharma – Advisory Committee/Board Member, Consultant, Other Financial or Material Support, data and safety monitoring board member. Immunic – Advisory Committee/Board Member, Consultant, Other Financial or Material Support, data and safety monitoring board member. Jazz Pharmaceuticals – Advisory Committee/Board Member, Consultant, Other Financial or Material Support, data and safety monitoring board member. Mapi Pharma – Advisory Committee/Board Member, Consultant, Other Financial or Material Support, data and safety monitoring board member. Medday – Advisory Committee/Board Member, Consultant, Other Financial or Material Support, data and safety monitoring board member. MedImmune/Viela Bio – Advisory Committee/Board Member, Consultant, Other Financial or Material Support, data and safety monitoring board member. Mylan – Advisory Committee/Board Member, Consultant, Other Financial or Material Support, data and safety monitoring board member. Neurogene – Advisory Committee/Board Member, Consultant, Other Financial or Material Support, data and safety monitoring board member. NIH – Grant/Research Support. NMSS – Grant/Research Support. Novartis – Advisory Committee/Board Member, Consultant, Grant/Research Support, Other Financial or Material Support, data and safety monitoring board member. Orion Biotechnology – Advisory Committee/Board Member, Consultant, Other Financial or Material Support, data and safety monitoring board member. Population Council – Advisory Committee/Board Member, Consultant, Other Financial or Material Support, data and safety monitoring board member. Receptos/Celgene/BMS – Advisory Committee/Board Member, Consultant, Other Financial or Material Support, data and safety monitoring board member. Roche/Genentech – Advisory Committee/Board Member, Consultant, Other Financial or Material Support, data and safety monitoring board member. Sanofi – Grant/Research Support, Speaker's Bureau. Sanofi/Genzyme – Advisory Committee/Board Member, Consultant, Other Financial or Material Support, data and safety monitoring board member. Teva – Advisory Committee/Board Member, Consultant, Other Financial or Material Support, data and safety monitoring board member. TG Therapeutics – Advisory Committee/Board Member, Consultant, Other Financial or Material Support, data and safety monitoring board member.

Bruce Cree: Alexion – Consultant. Atara – Consultant. Autobahn – Consultant. EMD Serono – Consultant. Genentech – Grant/Research Support. Novartis – Consultant. Sanofi – Consultant. TG Therapeutics – Consultant. Therini – Consultant.

Jeffrey Cohen: Adamas – Consultant. Atara – Consultant. Bristol Myers Squibb – Consultant. Convelo – Consultant. MedDay – Consultant. Multiple Sclerosis Journal – Other Financial or Material Support, served as an Editor. Mylan – Consultant.

Silvio Danese: AbbVie – Advisory Committee/Board Member, Consultant, Speaker's Bureau. Allergan – Advisory Committee/Board Member, Consultant, Speaker's Bureau. Biogen Idec – Advisory Committee/Board Member, Consultant, Speaker's Bureau. Boehringer Ingelheim – Advisory Committee/Board Member, Consultant, Speaker's Bureau. Celgene Corporation – Advisory Committee/Board Member, Consultant, Speaker's Bureau. Celltrion – Advisory Committee/Board Member, Consultant, Speaker's Bureau. Ferring – Advisory Committee/Board Member, Consultant, Speaker's Bureau. Hospira – Advisory Committee/Board Member, Consultant, Speaker's Bureau. Janssen – Advisory Committee/Board Member, Consultant, Speaker's Bureau. Johnson & Johnson – Advisory Committee/Board Member, Consultant, Speaker's Bureau. Merck – Advisory Committee/Board Member, Consultant, Speaker's Bureau. Merck Sharp & Dohme – Advisory Committee/Board Member, Consultant, Speaker's Bureau. Mundipharma – Advisory Committee/Board Member, Consultant, Speaker's Bureau. Pfizer – Advisory Committee/Board Member, Consultant, Speaker's Bureau. Sandoz – Advisory Committee/Board Member, Consultant, Speaker's Bureau. Takeda – Advisory Committee/Board Member, Consultant, Speaker's Bureau. Tigenix – Advisory Committee/Board Member, Consultant, Speaker's Bureau. UCB Pharma – Advisory Committee/Board Member, Consultant, Speaker's Bureau. Vifor – Advisory Committee/Board Member, Consultant, Speaker's Bureau.