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Sunday Poster Session

Category: IBD

P0727 - Efficacy and Safety of Filgotinib as Induction and Maintenance Therapy for Crohn’s Disease: Results From the Phase 3 Randomized, Double-Blind, Placebo-Controlled DIVERSITY1 Study

Sunday, October 22, 2023
3:30 PM – 7:00 PM PT
Location: Exhibit Hall
Séverine Vermeire, MD, PhD1, David T. Rubin, MD2, Mamoru Watanabe, MD, PhD3, Stefan Schreiber, MD4, Rajiv Mehta, MD, PhD5, Xavier Roblin, MD6, Mark C. Genovese, MD7, Tomasz Masior, MD8, Rahul Barron, MD, PhD8, Franck-Olivier Le Brun, MSc8, Silvio Danese, MD, PhD9
1UZ Leuven, Leuven, Vlaams-Brabant, Belgium; 2Inflammatory Bowel Disease Center, University of Chicago Medicine, Chicago, IL; 3Advanced Research Institute, Tokyo Medical and Dental University, Tokyo, Tokyo, Japan; 4University Hospital Schleswig-Holstein, Kiel, Schleswig-Holstein, Germany; 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 GmbH, Basel, Basel-Stadt, Switzerland; 9IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan, Lombardia, Italy

Introduction: We evaluated the efficacy and safety of filgotinib (FIL), an oral, once-daily, Janus kinase 1 preferential inhibitor, for the treatment of Crohn’s disease (CD).

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. Patients 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). Non-EU-specific co-primary endpoints at IND Study W10 and Maintenance (MNT) Study W58 were CDAI clinical remission (score < 150) and endoscopic response assessed by SES-CD score (≥ 50% reduction from baseline). FIL-treated patients were rerandomized 2:1 to their IND dose or PBO in the MNT Study if at W10 they had endoscopic response or were in PRO2 clinical remission (the EU-specific co-primary endpoint).

Results: In IND Studies A and B, 707 and 665 patients were randomized to FIL200 (n=223; n=204), FIL100 (n=245; n=230) or PBO (n=239; n=231), respectively. In the MNT Study, 481 patients were rerandomized to continue FIL or PBO treatment (FIL200–FIL200, n=118; FIL200–PBO, n=56; FIL100–FIL100, n=105; FIL100–PBO, n=56; PBO–PBO, n=146). Among treated patients, 89.3% (629/704), 83.8% (552/659) and 48.1% (230/478) completed the IND A, IND B and MNT studies, respectively. In the IND Studies at W10, a significantly higher proportion of patients in the FIL200 group vs PBO group were in CDAI clinical remission (IND A: 32.9% vs 19.8%; IND B: 26.7% vs 14.8%; both p < 0.05). The proportions of patients who had endoscopic response at W10 were not statistically significantly different for either FIL dose vs PBO (Figure). In the MNT Study at W58, the proportions of patients in CDAI clinical remission were not statistically significantly different for either FIL dose vs PBO. A significantly greater proportion of patients in the FIL200–FIL200 group vs FIL200–PBO group had endoscopic response at W58 (30.4% vs 9.4%; p = 0.0038). Secondary endpoints are summarized in the Table. FIL had a safety profile in CD that was consistent with that in UC.

Discussion: In the DIVERSITY1 study in CD, FIL200 was not superior to PBO based on both co-primary endpoints in IND. Nonetheless, FIL200 was efficacious in inducing CDAI clinical remission at W10. Among patients who had endoscopic response or were in PRO2 clinical remission at W10, FIL200 was efficacious in achieving endoscopic response at W58 in MNT.

Figure: Figure. Co-primary Endpoints (CDAI Clinical Remission and Endoscopic Response) at W10 of A) IND Study A and B) IND Study B, and at W58 of C) MNT Study of FIL in CD (Full Analysis Sets).

a: The Full Analysis Set for the MNT study includes all rerandomized patients who met the protocol definition of PRO2 clinical remission or endoscopic response at W10 and received at least one dose of FIL or PBO during the MNT study. The Full Analysis Set for the MNT study excluded 19 rerandomized patients (FIL200–FIL200, n=6; FIL200–PBO, n=3; FIL100–FIL100, n =7; FIL100–PBO, n=3).
Each co-primary endpoint comparison of FIL200 vs PBO was tested at the two-sided 0.05 significance level first. If the difference was statistically significant for both co-primary endpoints, the secondary endpoints and comparing FIL100 vs PBO for the co-primary endpoints were tested at the two-sided 0.025 significance level using hierarchical testing within each sequence.
CDAI clinical remission was defined as a CDAI score of less than 150.
Endoscopic response was defined as a reduction of at least 50% in Simple Endoscopic Score for CD from IND baseline.
CD, Crohn’s Disease; CDAI, Crohn’s Disease Activity Index; CI, confidence interval; FIL, filgotinib; FIL100, filgotinib 100 mg; FIL200, filgotinib 200 mg; IND, Induction; MNT, Maintenance; PBO, placebo; PRO2, two-item patient-reported outcomes; W10, week 10; W58, week 58.

IND Study, A or B (W10)

A
FIL200
n=222

A
FIL100
n=245

A
PBO
n=237

A
∆% FIL200 vs PBO (95% CI);
p value
and
 ∆% FIL100 vs PBO (95% CI);
p value

B
FIL200
n=202

B
FIL100
n=228

B
PBO
n=229

B
∆% FIL200 vs PBO (95% CI);
p value
and
∆% FIL100 vs PBO (95% CI);
p value

PRO2 clinical remission, n (%)

73/222 (32.9)

75/245 (30.6)

61/237 (25.7)

6.9 (−1.4, 15.2);
0.0963
and
4.2 (−3.9, 12.2);
0.3050

60/202 (29.7)

43/228 (18.9)

41/229 (17.9)

11.9 (3.7, 20.2);
0.0039
and
1.1 (−6.2, 8.5);
0.7556

CDAI clinical response, n (%)

116/222 (52.3)

113/245 (46.1)

94/237 (39.7)

12.0 (3.2, 20.8);
0.0074
and
5.5 (−3.2, 14.1);
0.2159

78/202 (38.6)

81/228 (35.5)

63/229 (27.5)

11.6 (2.6, 20.6);
0.0110
and
8.2 (−0.4, 16.7);
0.0593

MNT Study
(W58)

FIL200–FIL200
n=112

FIL200–PBO
n=53

∆% FIL200–FIL200 vs FIL200–PBO (95% CI);
p value

FIL100–FIL100
n=98

FIL100–PBO
n=53

∆% FIL100–FIL100 vs FIL100–PBO (95% CI);
p value

PRO2 clinical remission, n (%)

49/112 (43.8)

14/53 (26.4)

16.8 (2.0, 31.6);
0.0382

29/98 (29.6)

13/53 (24.5)

5.8 (−8.5, 20.0);
0.4263

CDAI clinical response, n (%)

51/112 (45.5)

18/53 (34.0)

10.9 (−4.7, 26.4);
0.1827

33/98 (33.7)

16/53 (30.2)

4.0 (−11.1, 19.2);
0.5944

6-month CS-free CDAI clinical remission, n (%)

17/50 (34.0)

5/25 (20.0)

14.0 (−5.1, 33.1); 
0.1900

2/41 (4.9)

3/25 (12.0)

−5.5 (−22.6, 11.6);
0.4248


Table: Table. Selected Secondary Endpoints in IND and MNT Studies of FIL in CD (Full Analysis Sets).
In line with the hierarchical testing strategy, any statistical significance for the secondary endpoints is nominal owing to the co-primary endpoints not being met in IND Study A, IND Study B or MNT Study. Therefore, no conclusions about the statistical significance of the secondary endpoints can be made.
PRO2 clinical remission was defined as an abdominal pain score of not more than 1 and a stool frequency score of not more than 3.
CDAI clinical response was defined as a reduction from IND baseline by at least 100 points or a CDAI score of less than 150.
Six-month CS-free CDAI clinical remission was defined as a CDAI score of less than 150, with no use of CS indicated for CD for at least 6 months prior to MNT Study W58 among patients with CS use at MNT baseline.
CD, Crohn’s Disease; CDAI, Crohn’s Disease Activity Index; CI, confidence interval; CS, corticosteroid; FIL, filgotinib; FIL100, filgotinib 100 mg; FIL200, filgotinib 200 mg; IND, Induction; MNT, Maintenance; PBO, placebo; PRO2, two-item patient reported outcome; W10, week 10; W58, week 58.


Disclosures:
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.
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.
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.
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.
Mark Genovese: Gilead Sciences – Employee.
Tomasz Masior: Galapagos – Employee, Stock Options.
Rahul Barron: Galapagos – Employee, Stock Options.
Franck-Olivier Le Brun: Galapagos – Employee, Stock Options.
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.


Séverine Vermeire, MD, PhD1, David T. Rubin, MD2, Mamoru Watanabe, MD, PhD3, Stefan Schreiber, MD4, Rajiv Mehta, MD, PhD5, Xavier Roblin, MD6, Mark C. Genovese, MD7, Tomasz Masior, MD8, Rahul Barron, MD, PhD8, Franck-Olivier Le Brun, MSc8, Silvio Danese, MD, PhD9. P0727 - Efficacy and Safety of Filgotinib as Induction and Maintenance Therapy for Crohn’s Disease: Results From the Phase 3 Randomized, Double-Blind, Placebo-Controlled DIVERSITY1 Study, ACG 2023 Annual Scientific Meeting Abstracts. Vancouver, BC, Canada: American College of Gastroenterology.