Filgotinib Misses Co-Primary Endpoints in Phase 3 DIVERSITY1 Study, Presented at ACG 2023

Séverine Vermeire, MD, PhD

Credit: IBD Leuven

Filgotinib did not meet either co-primary endpoint for superior clinical remission or endoscopic response versus placebo in treated patients with moderately to severely active Crohn disease (CD), according to results from the phase 3 DIVERSITY1 study.

Presented in an abstract at the American College of Gastroenterology (ACG) 2023 Annual Scientific Meeting in Vancouver, BC this weekend, findings suggested once-daily filgotinib 200 mg was nonetheless associated with efficacious clinical remission and endoscopic response at week 58 in the maintenance cohorts.¹

“While Crohn’s disease is a difficult-to-treat condition and a large proportion of patients enrolled in DIVERSITY had high disease activity and long-standing disease with prior exposure to multiple therapies, we are disappointed with the outcome of the induction studies,” investigator Séverine Vermeire, MD, PhD, research director of biomedical sciences at KU Leuven, said when topline DIVERSITY1 results were announced in February 2023.² “However, at the same time, we are encouraged by the confirmed safety profile and the clinical efficacy signs observed in the maintenance phase.”

A double-blind, randomized, placebo-controlled, phase 3 study, DIVERSITY1 assessed the safety and efficacy of filgotinib as an induction and maintenance treatment for moderately to severely active CD in both biologic-naive and biologic-experienced adult participants. In total, 1374 participants aged 18 – 75 years old were enrolled and randomized in a 1:1:1 ratio to either filgotinib 200 mg or 100 mg, or placebo once daily for 10 weeks in induction study A—including biologic-naive and biologic-experienced patients—or study B—including only biologic-experienced patients.¹

Investigators sought primary outcomes of Crohn's Disease Activity Index (CDAI) clinical remission, defined as score <150, and endoscopic response, defined as ≥50% reduction in Simple Endoscopic (SES-CD) score from baseline. These outcomes were measured at weeks 10 and 58.¹

In induction study A, 707 participants were randomized to filgotinib 200 mg (n = 223), filgotinib 100 mg (n = 245), and placebo (n = 239). In induction study B, 665 participants were randomized to filgotinib 200 mg (n = 204), filgotinib 100 mg (n = 230), and placebo (n = 231).¹

Patients treated with filgotinib were rerandomized 2:1 to their induction dose or placebo in the 58-week maintenance study if at week 10 they had endoscopic response or were in PRO2 clinical remission. In the maintenance study, 481 participants were rerandomized to continue filgotinib or placebo treatment: 118 patients remained on filgotinib 200 mg; 56 switched from filgotinib 200 mg to placebo; 105 remained on filgotinib 100 mg; 56 switched from filgotinib 100 mg to placebo; and 146 remained on placebo.¹

Among treated patients, 89.3%, 83.8%, and 48.1% completed the induction A, induction B, and maintenance studies, respectively. In the induction studies, a significantly higher proportion of patients in the filgotinib 200 mg group were in CDAI clinical remission at week 10 compared to those on placebo (induction A, 32.9% vs 19.8%; induction B, 26.7% vs 14.8%; both P <.05).¹

In the maintenance study, the proportions of patients in CDAI clinical remission were not statistically significantly different for both filgotinib 100 mg and 200 mg compared to placebo at week 58. Investigators noted a significantly greater proportion of patients remaining on filgotinib 200 mg (30.4%) achieved endoscopic response at week 58 compared to those who switched to placebo (9.4%; P = .0038).¹

“Filgotinib 200 mg was not superior to placebo based on both co-primary endpoints in induction,” investigators concluded.¹ “Nonetheless, filgotinib 200 mg was efficacious in inducing CDAI clinical remission at W10. Among patients who had endoscopic response or were in PRO2 clinical remission at W10, filgotinib 200 mg was efficacious in achieving endoscopic response at W58 in maintenance.”

References:

1. Vermeire S, Rubin D, Watanabe M, et al. 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. Abstract presented at: American College of Gastroenterology 2023; October 20 - 25; Toronto, BC. Accessed October 20, 2023.
2. Galapagos. Galapagos announces topline results from Phase 3 DIVERSITY trial of filgotinib in Crohn’s disease. February 8, 2023. Accessed October 20, 2023. https://www.glpg.com/press-release/3766/galapagos-announces-topline-results-from-phase-3-diversity-trial-of-filgotinib-in-crohn-s-disease