P0737 - Safety of Filgotinib in Crohn’s Disease Compared with Ulcerative Colitis: Data from the Phase 3 DIVERSITY1 and Phase 2b/3 SELECTION Studies

Sunday, October 22, 2023

3:30 PM – 7:00 PM PT

Location: Exhibit Hall

Presenting Author(s)

David Rubin, MD, FACG (he/him/his)

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

Stefan Schreiber, MD¹, Séverine Vermeire, MD, PhD², David T. Rubin, MD³, Silvio Danese, MD, PhD⁴, Rajiv Mehta, MD, PhD⁵, Xavier Roblin, MD⁶, Paul Kwon, MD⁷, Paul van Hoek, MD⁸, Tomasz Masior, MD⁹, Rahul Barron, MD, PhD⁹, Franck-Olivier Le Brun, MSc⁹, Mamoru Watanabe, MD, PhD¹⁰
¹University Hospital Schleswig-Holstein, Kiel, Schleswig-Holstein, Germany; ²UZ Leuven, Leuven, Vlaams-Brabant, Belgium; ³Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, IL; ⁴IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Lombardia, Italy; ⁵Surat Institute of Digestive Sciences Hospital, Surat, Gujarat, India; ⁶University Hospital of Saint-Étienne, Saint-Étienne, Pays de la Loire, France; ⁷Gilead Sciences, Inc., Foster City, CA; ⁸Galapagos NV, Mechelen, Antwerpen, Belgium; ⁹Galapagos GmbH, Basel, Basel-Stadt, Switzerland; ¹⁰Advanced Research Institute, Tokyo Medical and Dental University, Tokyo, Tokyo, Japan

Introduction: Filgotinib (FIL) is an oral, once-daily, Janus kinase 1 preferential inhibitor. We evaluated the safety of FIL in Crohn’s disease (CD) in the DIVERSITY1 study, comparing it with SELECTION data in ulcerative colitis (UC).¹

Methods: DIVERSITY1 (NCT02914561) was a phase 3, double-blind, placebo (PBO)-controlled trial in adults aged 18–75 years with moderately to severely active CD who were randomized 1:1:1 to FIL 200 mg (FIL200), FIL 100 mg (FIL100) or PBO once daily for 10 weeks in Induction (IND) Study A (biologic [bio]-naive and bio-experienced) or B (bio-experienced). FIL-treated patients who met either co-primary endpoint (clinical remission or endoscopic response) at week 10 were rerandomized 2:1 to their IND dose or PBO in the Maintenance (MNT) Study to week 58. The SELECTION (NCT02914522; UC) and DIVERSITY1 (CD) trials evaluated the same FIL doses for similar IND and MNT periods.¹Safety outcomes from the two trials were compared.

Results: In CD IND studies A and B, 707 and 665 patients respectively, were randomized to FIL200 (n=223; n=204), FIL100 (n=245; n=230) or PBO (n=239; n=231). In the MNT study, 481 patients were randomized (FIL200-FIL200, n=118; FIL200-PBO, n=56; FIL100-FIL100, n=105; FIL100-PBO, n=56; PBO-PBO, n=146). Safety outcomes in CD and UC IND studies are reported in the Table. In the MNT studies, infections were reported in 25.5–33.9% (CD) and 22.6–35.1% (UC) of patients; serious infections were reported in 1.9% (CD) and 1.2% (UC) of patients. Malignancy (excluding non-melanoma skin cancer) in the MNT studies was reported for FIL100-FIL100 (n=1; 1.0%) in CD, and for FIL200-FIL200 (n=1; 0.5%) and FIL100-FIL100 (n=1; 0.6%) in UC. In the MNT studies, venous thromboembolism (VTE) was reported in one patient with CD (FIL200-FIL200; 0.8%) and one patient with UC (PBO-PBO; 1.1%). Major adverse cardiovascular events (MACEs) in the MNT studies were reported in one patient with CD (0.4%; IND Study B FIL100) and five patients with UC (IND PBO [n=1; 0.4%]; FIL200-FIL200 [n=2; 1.0%]; FIL100-FIL100 [n=1; 0.6%]; PBO-PBO [n=1; 1.1%]). No deaths were reported in DIVERSITY1. Two deaths were reported in SELECTION; neither was considered treatment-related by the investigator.

Discussion: FIL treatment was well tolerated. FIL had a safety profile in CD that was generally consistent with that in UC. No new safety signals were observed.¹ The numbers of malignancy, VTE and MACE events for FIL were low in CD and UC clinical trials.¹

1. Feagan BG et al. Lancet 2021;397:2372–84.

Patients, n (%)	DIVERSITY1 (Crohn’s disease)						SELECTION¹ (ulcerative colitis)
	IND Study A			IND Study B			IND Studies A & B	IND Studies A & B	IND Studies A & B
	FIL200 n=222	FIL100 n=245	PBO n=237	FIL200 n=202	FIL100 n=228	PBO n=229	FIL200 n=507	FIL100 n=562	PBO n=279
TEAEs	114 (51.4)	136 (55.5)	137 (57.8)	141 (69.8)	154 (67.5)	156 (68.1)	272 (53.6)	283 (50.4)	157 (56.3)
Serious TEAEs	18 (8.1)	16 (6.5)	15 (6.3)	19 (9.4)	36 (15.8)	26 (11.4)	22 (4.3)	28 (5.0)	13 (4.7)
TEAEs leading to discontinuation of study drug	16 (7.2)	15 (6.1)	13 (5.5)	24 (11.9)	31 (13.6)	19 (8.3)	23 (4.5)	20 (3.6)	14 (5.0)
Infections	39 (17.6)	38 (15.5)	41 (17.3)	47 (23.3)	58 (25.4)	59 (25.8)	92 (18.1)	82 (14.6)	39 (14.0)
Serious infections	8 (3.6)	2 (0.8)	0	5 (2.5)	8 (3.5)	7 (3.1)	3 (0.6)	6 (1.1)	3 (1.1)
GI perforations^a	2 (0.9)	4 (1.6)	0	1 (0.5)	2 (0.9)	2 (0.9)	0	0	1 (0.4)
Malignancies (excluding non-melanoma skin cancer)	0	0	0	0	0	0	1 (0.2)	1 (0.2)	0
VTE^b	0	0	0	0	0	1 (0.4)	1 (0.2)	0	0
MACE^b	0	0	0	0	1 (0.4)	0	0	0	1 (0.4)

Table: Table. Summary of Safety Outcomes in the DIVERSITY1 and SELECTION IND Studies.

Safety was assessed throughout the study in all patients who received at least one dose of FIL or PBO within each study part.

a: In the DIVERSITY1 study, the post hoc adjudication of GI perforations by an external expert committee determined that none of the events were considered related to study treatment, but were related to underlying disease progression and/or colonoscopies.

b: In the DIVERSITY1 and SELECTION studies, MACEs and VTE events were adjudicated by an external expert committee. This was a post hoc adjudication of events in SELECTION.

FIL, filgotinib; FIL100, filgotinib 100 mg; FIL200, filgotinib 200 mg; GI, gastrointestinal; IND, induction; MACE, major adverse cardiovascular event; PBO, placebo; TEAE, treatment-emergent adverse event; VTE, venous thromboembolism.

Disclosures:

Stefan Schreiber: AbbVie – Personal fees. Amgen – Personal fees. Arena Pharmaceuticals – Personal fees. Biogen – Personal fees. Bristol Myers Squibb – Personal fees. Celgene – Personal fees. Celltrion Healthcare – Personal fees. Dr. Falk Pharma – Personal fees. Eli Lilly – personal fees. Ferring Pharmaceuticals – personal fees. Fresenius Kabi – Personal fees. Galapagos – Personal fees. Gilead – Personal fees. Hikma Pharmaceuticals – Personal fees. I-Mab – Personal fees. Janssen Pharmaceuticals – Personal fees. Morphic – Personal fees. MSD – Personal fees. Mylan – Personal fees. Pfizer – Personal fees. Protagonist – Personal fees. ProventionBio – Personal fees. Sandoz/Hexal – personal fees. Takeda – Personal fees. Theravance Biopharma – Personal fees. UCB – personal fees.

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.

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.

Rajiv Mehta indicated no relevant financial relationships.

Xavier Roblin: AbbVie – personal fees. Amgen – personal fees. Bristol Myers Squibb – personal fees. Celltrion – personal fees. Eli Lilly – personal fees. Galapagos – personal fees. Janssen Pharmaceuticals – personal fees. MSD – personal fees. Pfizer – personal fees. Takeda – personal fees. Theradiag – personal fees.

Paul Kwon: Gilead Sciences – Employee.

Paul van Hoek: AOP Health – Consultant. Aspen – Consultant. Astellas Pharma – Consultant. Galapagos – Consultant. Janssen – Employee. MSD – Employee. Sanofi – Consultant. Schering-Plough – Employee.

Tomasz Masior: Galapagos – Employee, Stock Options.

Rahul Barron: Galapagos – Employee, Stock Options.

Franck-Olivier Le Brun: Galapagos – Employee, Stock Options.

Mamoru Watanabe: AbbVie – Consultant, Grant/Research Support. Alfresa Pharma – Grant/Research Support. Celltrion Healthcare – honoraria. EA Pharma – Consultant, Grant/Research Support, honoraria. Eli Lilly Japan – Consultant, honoraria. Gilead Sciences – Consultant, honoraria. Janssen Pharmaceutical – honoraria. JIMRO – honoraria. Kissei Pharmaceutical – Grant/Research Support, honoraria. Kyorin Pharmaceutical – Grant/Research Support. Mitsubishi Tanabe Pharma – Grant/Research Support, honoraria. Mochida Pharmaceutical – Grant/Research Support, honoraria. Nippon Boehringer Ingelheim – Consultant, honoraria. Nippon Kayaku – Grant/Research Support. Pfizer Japan – honoraria. Takeda – Consultant, Grant/Research Support, Honoraria. Zeria Pharmaceutical – Grant/Research Support, honoraria.