Filgotinib (GLPG0634), an Oral JAK1 Selective Inhibitor Is Effective in Combination with Methotrexate in Patients with Active Rheumatoid Arthritis: Results from a Phase 2B Dose Ranging Study

R Westhovens¹, Rieke Alten², Dace Pavlova³, Favio Enríquez-Sosa⁴, Minodora Mazur⁵, Maria Greenwald⁶, Annegret Van der Aa⁷, Frédéric Vanhoutte⁷, Chantal Tasset⁷ and Pille Harrison⁷, ¹Skeletal Biology and Engineering Research Center, Department of Development and Regeneration, KU Leuven, Leuven, Belgium, KU Leuven, Leuven, Belgium, ²Internal Medicine, Rheumatology & Clinical Immunology, Schlosspark-Klinik, University Medicine Berlin, Berlin, Germany, ³LTD M & M Centrs, Carnikava, Latvia, ⁴CLINSTILE, S.A. DE C.V, Mexico, Mexico, ⁵IMSP Institul de Cardiologie, Chisinau, Moldova, ⁶Desert Medical Advances, Palm Desert, CA, ⁷Galapagos NV, Mechelen, Belgium

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: clinical trials, Effective, Janus kinase (JAK), rheumatoid arthritis (RA) and treatment

Session Information

Date: Sunday, November 8, 2015

Session Title: Rheumatoid Arthritis-Small Molecules, Biologics and Gene Therapy II: Small Molecular Targeted Therapies

Session Type: ACR Concurrent Abstract Session

Session Time: 4:30PM-6:00PM

Background/Purpose: Filgotinib (GLPG0634) is a novel oral, potent and selective JAK1 inhibitor that has previously demonstrated efficacy in combination with methotrexate (MTX) in treating rheumatoid arthritis (RA) in 4-week phase 2A studies with an acceptable safety profile. The purpose of this study was to evaluate efficacy and safety of different doses and dose regimens of filgotinib versus placebo (PBO) in patients with active RA with inadequate response to MTX.

Methods: Patients with active RA on stable dose of MTX were randomized 1:1:1:1:1:1:1 in a double blinded manner to receive either PBO or one of three doses of filgotinib (50mg, 100mg or 200mg) as once (qd) or twice daily (bid) regimen for 24 weeks (DARWIN 1 study). The primary endpoint was the proportion of patients achieving ACR 20 response at week 12. Reported data are from the planned 12 weeks analysis.

Results: Of 594 randomized and treated patients, 76-86% were females with a mean age across groups of 52-55 years, mean duration of RA of 7-10 years and DAS28(CRP) at baseline ranging from 6.0-6.2. Patients were well distributed across different geographical regions. At week 12, a statistically significant higher ACR20 response versus PBO was observed with 200mg daily dose. For other key efficacy endpoints (ACR50, ACR-N, DAS28(CRP), CDAI, SDAI) all doses showed significant differences versus PBO. No statistically significant difference between qd and bid regimens was seen. By week 12, 24-50% of patients on filgotinib achieved low disease activity (DAS28(CRP)≤ 3.2) in a dose dependent manner, compared to 14% on PBO. Onset of efficacy was rapid for ACR-N, DAS28(CRP) and SDAI with significant differences seen from week 1 onwards at 200mg daily dose.

Table 1. Summary of the ACR/DAS28(CRP)/CDAI responses after 12 weeks treatment:

		Once-daily dosing			Twice-daily dosing
	Placebo n=86	50mg n=82	100mg n=85	200mg n=86	25mg n=86	50mg n=85	100mg n=84
ACR20, NRI¹, %	45	56	62	69*	57	59	80***
ACR50, NRI, %	15	32*	39**	43***	28*	34*	55***
ACR70, NRI, %	8	16	20	24*	14	19	31**
ACR-N, LOCF², %	23	34*	38**	42***	33*	36*	51***
DAS28(CRP), mean change from BL³, LOCF	-1.2	-1.8*	-2.2***	-2.5***	-1.9**	-2.1***	-2.8***
CDAI⁴, mean change from BL, LOCF	-17	-20	-24**	-26***	-21*	-23**	-29***

* p< 0.05 vs. placebo; ** p<0.01 vs. placebo; *** p<0.001 vs. placebo; ACR scores based on ITT analysis. ¹Non-responder imputation. ² Last observation carried forward.³ Baseline.⁴Clinical Disease Activity Index.

Conclusion: Over 12 weeks, filgotinib in combination with MTX demonstrated consistent efficacy on signs and symptoms of active RA with a rapid onset of action. The safety profile was overall favorable and consistent with previous studies conducted in RA with filgotinib.

Disclosure: R. Westhovens, Roche Pharmaceuticals, 2,Bristol-Myers Squibb, 8,Janssen, Galapagos, 5; R. Alten, None; D. Pavlova, None; F. Enríquez-Sosa, None; M. Mazur, None; M. Greenwald, None; A. Van der Aa, Galapagos, 3; F. Vanhoutte, Galapagos NV, 3; C. Tasset, Galapagos, 3; P. Harrison, Galapagos, 3.

To cite this abstract in AMA style:

Westhovens R, Alten R, Pavlova D, Enríquez-Sosa F, Mazur M, Greenwald M, Van der Aa A, Vanhoutte F, Tasset C, Harrison P. Filgotinib (GLPG0634), an Oral JAK1 Selective Inhibitor Is Effective in Combination with Methotrexate in Patients with Active Rheumatoid Arthritis: Results from a Phase 2B Dose Ranging Study [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). http://acrabstracts.org/abstract/filgotinib-glpg0634-an-oral-jak1-selective-inhibitor-is-effective-in-combination-with-methotrexate-in-patients-with-active-rheumatoid-arthritis-results-from-a-phase-2b-dose-ranging-study/. Accessed July 9, 2017.

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