ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1909

Long Term Safety of Filgotinib in the Treatment of Rheumatoid Arthritis: Week 84 Data from a Phase 2b Open-Label Extension Study

Mark C. Genovese1, Arthur Kavanaugh2, Kevin Winthrop3, Maria Greenwald4, Lucia Ponce5, Favio Enriquez Sosa6, Mykola Stanislavchuk7, Minodora Mazur8, Alberto Spindler9, Regina Cseuz10, Natalya Nikulenkova11, Maria Glowacka-Kulesz12, Istvan Szombati13, Anna Dudek14, Neelufar Mozaffarian15, Joy Greer15, Xiao Ding15, Pille Harrison16, Annegret Van der Aa16, René Westhovens17 and Rieke Alten18, 1Stanford University Medical Center, Palo Alto, CA, 2Medicine, University of California, San Diego, La Jolla, CA, 3Oregon Health Sciences University, Portland, OR, 4Desert Medical Advances, Palm Desert, CA, 5Consulta Privada Dra. Lucia Ponce, Temuco, Chile, 6Clinstile SA de CV, Col., Mexico City, Mexico, 7Vinnitsa Regional Clinical Hospital, Vinnitsa, Ukraine, 8IMSP Inst. de Cardiologie, Chisinau, Moldova, The Republic of, 9Centro Médico Privado de Reumatología, Centro Médico Privado de Reumatología, Argentina, 10Revita Reumatologiai Rendelo, Budapest, Hungary, 11Vladimir Reg Clin Hosp, Vladimir, Russian Federation, 12Silesiana Centrum Medyczne, Wroclawska, Poland, 13QUALICLINIC Kft., Budapest, Hungary, 14Centrum Medyczne AMED Warszawa Targówek, Warszawa, Poland, 15Gilead Sciences, Inc, Foster City, CA, 16Galapagos NV, Mechelen, Belgium, 17KU Leuven Department of Development and Regeneration, Skeletal Biology and Engineering Research Center, Leuven, Belgium, 18Internal Medicine, Rheumatology & Clinical Immunology, Schlosspark-Klinik, University Medicine Berlin, Berlin, Germany

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: , ,

Session Information

Date: Monday, November 6, 2017

Title: Rheumatoid Arthritis – Small Molecules, Biologics and Gene Therapy II: Trials Therapy

Session Type: ACR Concurrent Abstract Session

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

Background/Purpose: Filgotinib is an orally administered, selective inhibitor of Janus Kinase 1 (JAK1) currently in Phase 3 development for the treatment of rheumatoid arthritis (RA).

Methods: Previously, two 24-week Phase 2b studies were conducted in subjects with moderately to severely active RA (DARWIN 1, DARWIN 2; Ref 1, 2). Upon completing one of these studies, subjects could receive open-label filgotinib in the DARWIN 3 long-term follow-up study, given as 200 mg QD (100 mg QD for males in the US) or 100 mg BID. This report summarizes safety data from the first dose of filgotinib in DARWIN 1, 2 or 3 until the time that the last subject completed 84 weeks of filgotinib dosing. Efficacy is summarized for all subjects through Week 84 of DARWIN 3.

Results: Ninety percent of subjects (790 of 877) completed the Phase 2b studies, and 739 (84%) enrolled in DARWIN 3; 603 (82%) were female and the mean age was 53 years; 560 completed 84 weeks of filgotinib dosing. When the last subject completed 84 weeks in DARWIN 3, 520 (70.4%) subjects remained on study and 219 (29.6%) had discontinued. Most frequent reasons for discontinuation were positive/indeterminate QuantiFERON (10.3%; no active tuberculosis), protocol specified adverse event (AE) stopping rules (6.8%) and withdrawal of consent (5.8%). Cumulative patient years of exposure (PYE) were 1708 with a median time on study drug of 917 days (range 64 to 1329 days). A summary of safety events and laboratory abnormalities are summarized below. Based on ‘observed case’ analysis, 86%, 69%, and 47% of 560 subjects achieved ACR20/50/70, respectively, and 71% (386/543) achieved DAS28-CRP ≤3.2.

 

Conclusion: Filgotinib long-term follow-up data demonstrate a favorable safety and durable efficacy profile in subjects with RA, consistent with prior reports.

 

Table 1: Summary of Exposure and Safety Outcomes Per 100 PYE

 

Filgotinib + MTX

Filgotinib Monotherapy

Total (N=739)

 

100 mg BID (N=251)

100 mg QD* (N=9)

200 mg QD (N=251)

100 mg BID (N=1)

100 mg QD* (N=6)

200 mg QD (N=221)

Total FIL patient years of exposure (PYE)

593.5

21.8

595.5

0.6

10.6

485.8

1707.8

Median FIL exposure (days)

936

896

930

222

780

886

917

TEAEs/100PYE#

153.3

77.9

146.4

329.1

151.4

149.9

149.0

Serious TEAEs/100PYE#

6.2

0

3.2

0

9.5

7.8

5.6

TEAEs for Infections/100PYE

44.5

9.2

41.1

0

56.8

38.3

41.2

Serious TEAEs for Infections/100PYE

1.5

0

0.7

0

9.5

2.5

1.5

Malignancy (excluding NMSC†)/100PYE

0.7

0

0.2

0

0

0.8

0.5

*Treatment group is comprised of male subjects located in the US only

†Non-melanoma skin cancer

Table 2: Treatment Emergent Laboratory Abnormalities Per 100 PYE

 

Filgotinib + Methotrexate

Filgotinib Monotherapy

Total (N=739)

 

100 mg BID (N=251)

100 mg QD* (N=9)

200 mg QD (N=251)

100 mg BID (N=1)

100 mg QD* (N=6)

200 mg QD (N=221)

Hemoglobin/100 PYE

    Grade 2

4.4

0

7.9

0

0

6.6

6.1

    Grade 3

0.5

0

0

0

0

0

0.2

    Grade 4

0

0

0

0

0

0

0

Lymphocytes/100 PYE

    Grade 2

9.1

0

8.4

0

0

4.5

7.4

    Grade 3

1.0

0

0.8

0

0

0.4

0.8

    Grade 4

0

0

0.2

0

0

0

0.1

Neutrophils/100 PYE

    Grade 2

1.2

0

2.0

0

0

2.3

1.8

    Grade 3

0.2

0

0.2

0

0

0

0.1

    Grade 4

0.2

0

0

0

0

0.2

0.1

Platelets/ 100 PYE

    Grade 2

0.2

0

0.3

0

0

0

0.2

    Grade 3

0

0

0.2

0

0

0

0.1

    Grade 4

0

0

0.2

0

0

0

0.1

ALT/100PYE

    Grade 2

2.9

0

2.2

0

0

0.2

1.8

    Grade 3

0.3

0

0.2

0

0

0.2

0.2

    Grade 4

0

0

0

0

0

0

0

Creatinine/100PYE

    Grade 2

0

0

0

0

0

0.2

0.1

    Grade 3

0

0

0

0

0

0

0

    Grade 4

0

0

0

0

0

0

0

Toxicity Grading Scale Used:  CTCAE Version 3.0

*Treatment group includes male subjects located in the US only

Table 3: Treatment Emergent Laboratory Abnormalities for Lipids Per 100 PYE

 

Filgotinib + Methotrexate

Filgotinib Monotherapy

Total (N=739)

 

100 mg BID (N=251)

100 mg QD* (N=9)

200 mg QD (N=251)

100 mg BID (N=1)

100 mg QD* (N=6)

200 mg QD (N=221)

LDL/100 PYE

    100 – 129 mg/dL

42.8

114.5

54.1

0

18.9

53.1

50.4

    130 – 159 mg/dL

51.2

22.9

45.8

0

9.5

55.2

49.8

    160 – 189 mg/dL

28.6

0

32.2

0

28.4

30.9

30.2

    ≥ 190 mg/dL

18.0

0

5.7

0

0

18.7

13.6

HDL/100 PYE

    <40 mg/dL

5.7

41.2

7.6

0

0

7.2

7.2

    40 – 60 mg/dL

23.8

41.2

17.1

0

18.9

12.4

18.4

Total Cholesterol/100 PYE

    200 – 239 mg/dL

78.5

87.0

79.3

0

66.2

94.3

83.3

    ≥ 240 mg/dL

61.0

0

64.3

0

37.8

71.4

64.2

Grading based on ATPIII Classification

*Treatment group includes male subjects located in the US only

 

References

1. Westhovens R, et al. Ann Rheum Dis 2017;76:998-1008; 2. Kavanaugh A, et al.Ann Rheum Dis 2017;76:1009-1019.

 

Disclosure: M. C. Genovese, Gilead, 5,Galapagos NV, 5,AbbVie, 5,Eli Lilly and Company, 5; A. Kavanaugh, Gilead Sciences, Inc, 5,Galapagos NV, 5,Pfizer Inc, 5,AbbVie, 5,Eli Lilly and Company, 5; K. Winthrop, Galapagos NV, 5,Pfizer Inc, 5,AbbVie, 5,Eli Lilly and Company, 5; M. Greenwald, Pfizer Inc, 5,Eli Lilly and Company, 5; L. Ponce, None; F. Enriquez Sosa, None; M. Stanislavchuk, None; M. Mazur, None; A. Spindler, None; R. Cseuz, None; N. Nikulenkova, None; M. Glowacka-Kulesz, None; I. Szombati, None; A. Dudek, None; N. Mozaffarian, Gilead Sciences, Inc, 1,Gilead Sciences, Inc, 3,Eli Lilly and Company, 1; J. Greer, Gilead Sciences, Inc, 1,Acteta Pharma, 1,Gilead Sciences, Inc, 3; X. Ding, Gilead Sciences, Inc, 1,Gilead Sciences, Inc, 3; P. Harrison, Galapagos NV, 1,Galapagos NV, 3; A. Van der Aa, Galapagos NV, 1,Galapagos NV, 3; R. Westhovens, Bristol-Myers Squibb, 2,Roche Pharmaceuticals, 2,CellTrion, 5,Galapagos NV, 5; R. Alten, Galapagos NV, 2.

To cite this abstract in AMA style:

Genovese MC, Kavanaugh A, Winthrop K, Greenwald M, Ponce L, Enriquez Sosa F, Stanislavchuk M, Mazur M, Spindler A, Cseuz R, Nikulenkova N, Glowacka-Kulesz M, Szombati I, Dudek A, Mozaffarian N, Greer J, Ding X, Harrison P, Van der Aa A, Westhovens R, Alten R. Long Term Safety of Filgotinib in the Treatment of Rheumatoid Arthritis: Week 84 Data from a Phase 2b Open-Label Extension Study [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/long-term-safety-of-filgotinib-in-the-treatment-of-rheumatoid-arthritis-week-84-data-from-a-phase-2b-open-label-extension-study/. Accessed .

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