EULAR conference, 13 June 2019

Efficacy of filgotinib vs placebo in active psoriatic arthritis: patient-level data from EQUATOR, a randomized phase 2 study

P. Mease1, D. Gladman2, F. Van den Bosch3, M. Stanislavchuk4, A. Rychlewska-Hanczewska5, C. Tasset6, L. Meuleners6, R. Besuyen7, J. Gao8, M. Trivedi8, L. Coates9, P. Helliwell10

1Swedish Medical Center/Providence St Joseph Health and University of Washington, Seattle, United States of America; 2University of Toronto and Krembil Research Institute, Toronto Western Hospital, Toronto, Canada; 3University of Ghent, Department of

Rheumatology, Ghent, Belgium; 4National Pirogov Memorial Medical University, Vinnytsya, Ukraine; 5Ai Centrum Medyczne sp. z o.o. sp.k., Poznan, Poland; 6Galapagos NV, Mechelen, Belgium; 7Galapagos BV, Leiden, Netherlands; 8Gilead Sciences Inc, Foster City,

United States of America; 9University of Oxford, Oxford, United Kingdom; 9Leeds Institute of Rheumatic and Musculoskeletal Medicine, Leeds, United Kingdom

http://dx.doi.org/10.1016/S0140-6736(18)32483-8

Disclosures

♦ PJ Mease: Abbvie, Amgen, BMS, Boehringer Ingelheim, Celgene, Galapagos, Genentech, Gilead, Janssen, Eli Lilly, Novartis, Pfizer, SUN, UCB

♦ D Gladman: Abbvie, Amgen, BMS, Celgene, Eli Lilly, Galapagos, Gilead, Janssen, Novartis, Pfizer, UCB

♦ F Van den Bosch: Abbvie, Bristol-Myers Squibb, Eli Lilly, Galapagos, Janssen, Merck, Novartis, Pfizer, UCB

♦ M Stanislavchuk: no conflicts of interest♦ A Rychlewska-Hanczewska: national study coordinator, Galapagos, Gilead Sciences♦ C Tasset, L Meuleners, R Besuyen: Galapagos employees♦ J Gao, M Trivedi: Gilead Sciences employees♦ LC Coates: Abbvie, Amgen, Celgene, Galapagos, Janssen, Lilly, Novartis, Pfizer, Prothena, Sun

pharma, UCB♦ PS Helliwell: Abbvie, Amgen, Celgene, Galapagos, Janssen, Novartis, Pfizer, UCB

2

Filgotinib Background

3

Janus kinases (JAKs) play a key role in cytokine signalling— JAK1 is involved in numerous (pro)inflammatory cytokine signaling

— JAK2 mediates GM-CSF, EPO, TPO, GH, PRL signaling

— JAK3 has an effect on γ-chain cytokines critical for lymphocyte function

— TYK2 mediates Type1 IFN and IL-12/IL-23 signaling

Yamaoka K et al., Genome Biology 2004; 5(12):253

FILGOTINIB

Filgotinib, oral JAK1 selective inhibitor— 30-fold selective over JAK2 in whole blood assay

— t1/2 = 5–11h

— In addition, there is an active metabolite with t1/2 = 21–27h

— Both block cytokine signaling through inhibition of STAT phosphorylation

— Demonstrated efficacy and consistent safety profile in CD and RA

GM-CSF = Granulocyte-macrophage colony-stimulating factor; EPO = erythropoietin; TPO = thrombopoietin; GH = growth hormone; PRL = prolactin

Study ObjectivesPh2 EQUATOR study with filgotinib in PsA

4

♦ Primary objective of this analysis– Evaluate time to first response on patient-

level and individual duration of response, comparing filgotinib to placebo on signs and symptoms of psoriatic arthritis

♦ Secondary objectives– Evaluate effect of filgotinib compared to

placebo on signs and symptoms of psoriatic arthritis, psoriasis, enthesitis, physical function, fatigue, quality of life

– Evaluate safety and tolerability of filgotinib

♦ Inclusion Criteria – PsA for at least 12 weeks prior to screening (CASPAR)

– Active PsA: ≥5 tender and ≥5 swollen joints

– Active or documented history of plaque psoriasis

– Insufficient response or intolerance to ≥1 csDMARD• csDMARDs could be continued during the study provided

patient received this treatment for ≥12 weeks prior to screening and was on stable dose for 4 weeks prior to baseline

♦ Exclusion Criteria – Prior treatment with

• bDMARDs, except prior use of 1 anti-TNF agent• tsDMARDs

– Systemic steroids of ≥10 mg/day prednisone or equivalent

Study DesignPh2 EQUATOR study with filgotinib in PsA

5

♦ Mixed population – Anti-TNF naive and anti-TNF previously-exposed– Monotherapy and add-on to csDMARDs

Week 16Baseline

Primary endpoint

Screening Randomization OLE(N=122)D-28 1:1

filgotinib 200 mg qd (N=65)

placebo (N=66)

qd= once daily; OLE= open label extension study

Total N=131

Demographics Ph2 EQUATOR study with filgotinib in PsA

6

Filgotinib (N=65) Placebo (N=66)

Female, n (%) 36 (55.4) 30 (45.5)

Age, mean, years 49 50

Weight, mean, kg 81 87

BMI, mean, kg/m² 28.6 30.1

Duration of PsA, mean, years (since diagnosis) 7 7

Prior aTNF use, n (%) 11 (16.9) 9 (13.6)

Concurrent csDMARD use, n (%) 47 (72.3) 50 (75.8)

Concurrent steroid use, n (%) 17 (26.2) 16 (24.2)

Baseline disease characteristicsPh2 EQUATOR study with filgotinib in PsA

7

Filgotinib (N=65) Placebo (N=66)

TJC68, mean 18.3 21.6

SJC66, mean 11.6 12.7

HAQ-DI, mean 1.43 1.36

DAS28(CRP), mean 4.9 5.1

hsCRP, mean, mg/L 13.9 10.9

hsCRP ≥ULN, n (%) 25 (38.5) 17 (25.8)

Enthesitis, n (%) 38 (58.5) 49 (74.2)

SPARCC enthesitis (1) 4.9 5.5

LEI (enthesitis), mean (2) 2.8 2.6

≥3% BSA of psoriasis, n (%) 42 (64.6) 40 (60.6)

PASI, mean (3) 10.9 11.7

ULN hsCRP = 10 mg/L(1) full analysis set with enthesitis at baseline (SPARCC Enthesitis Index >0); (2) full analysis set with enthesitis at baseline (LEI >0) ;(3) full analysis set with baseline BSA ≥3%

ACR20 (primary endpoint), ACR50 and ACR70 at Week 16Ph2 EQUATOR study with filgotinib in PsA

80.0

80.0

33.3

47.7

15.223.1

6.1

**

***

***

0

10

20

30

40

50

60

70

80

90

100

ACR20 ACR50 ACR70

**: p<0.01; ***: p<0.001 PlaceboN=66

FilgotinibN=65

Primary endpoint

ACR responses, NRI% responders

NRI=non-responder imputation

ACR20Ph2 EQUATOR study with filgotinib in PsA

9

9

ACR20, response over timeACR20, time to first response, OC

ACR50Ph2 EQUATOR study with filgotinib in PsA

10

10

ACR50, time to first response, OC ACR50, response over time

ACR70Ph2 EQUATOR study with filgotinib in PsA

11

ACR70, time to first response, OC ACR70, response over time

MDA at Week 16Ph2 EQUATOR study with filgotinib in PsA

12

% responders

MDA = minimal disease activity (at least 5 out of 7: TJC68 ≤1, SJC66 ≤1, PASI ≤1 or BSA ≤3%, pain ≤15, PtGADA ≤20, HAQ-DI ≤0.5, SPARCC enthesitis ≤1); NRI=non-responder imputation

23.1

9.10

10

20

30

40

50

60

70

80

90

100

FIL N=65 PBO N=66

MDA, NRI

*

*: p<0.05

MDAPh2 EQUATOR study with filgotinib in PsA

13

13

MDA, time to first response, OC MDA, response over time

MDA = minimal disease activity (at least 5 out of 7: TJC68 ≤1, SJC66 ≤1, PASI ≤1 or BSA ≤3%, pain ≤15, PtGADA ≤20, HAQ-DI ≤0.5, SPARCC enthesitis ≤1); NRI=non-responder imputation

DAPSA low disease activity at Week 16Ph2 EQUATOR study with filgotinib in PsA

14

% responders

DAPSA = Disease Activity Index for Psoriatic Arthritis = TJC68 + SJC66 + PtGADA + Pain VAS + CRP (mg/dL); LDA = Low Disease Activity = DAPSA ≤ 14; NRI=non-responder imputation

49.2

15.2

0

10

20

30

40

50

60

70

80

90

100

FIL N=65 PBO N=66

DAPSA low disease activity, NRI

***

***: p<0.001

DAPSA Low Disease ActivityPh2 EQUATOR study with filgotinib in PsA

15

15

DAPSA LDA, time to first response, OC DAPSA LDA, response over time

DAPSA = Disease Activity Index for Psoriatic Arthritis = TJC68 + SJC66 + PtGADA + Pain VAS + CRP (mg/dL); LDA = Low Disease Activity = DAPSA ≤ 14; NRI=non-responder imputation

HAQ-DI response at Week 16 Ph2 EQUATOR study with filgotinib in PsA

16

% responders

HAQ-DI = health assessment questionnaire disease severity index, FAS with baseline value ≥0.35 (FIL N=63; PBO N=62); MCID = minimal clinically important difference = change from baseline ≤ -0.35; NRI = non-responder imputation

65.1

41.9

0

10

20

30

40

50

60

70

80

90

100

FIL N=63 PBO N=66

HAQ-DI MCID, NRI

**

**: p<0.01

HAQ-DI responsePh2 EQUATOR study with filgotinib in PsA

17

HAQ-DI MCID, time to first response, OC HAQ-DI MCID, response over time

HAQ-DI = health assessment questionnaire disease severity index, FAS with baseline value ≥0.35 (FIL N=63; PBO N=62); MCID = minimal clinically important difference = change from baseline ≤ -0.35; OC = observed case

PASI75 at Week 16Ph2 EQUATOR study with filgotinib in PsA

18

% responders

**: p<0.01

PASI75=Psoriasis Area and Severity Index 75%; Full Analysis Set with ≥ 3% BSA at baseline (FIL N=42; PBO N=40); BSA=body surface area; NRI=non-responder imputation

45.2

15

0

10

20

30

40

50

60

70

80

90

100

% change from baseline ≤-75%FIL N=42 PBO N=40

PASI75, NRI

**

PASI75Ph2 EQUATOR study with filgotinib in PsA

PASI75, time to first response, OC PASI75, response over time

PASI75=Psoriasis Area and Severity Index 75%; Full Analysis Set with ≥ 3% BSA at baseline; BSA=body surface area; OC=observed case;

Pruritus at Week 16Ph2 EQUATOR study with filgotinib in PsA

20

% respondersPruritus, NRI

**: p<0.01

Pruritus responder=Pruritus NRS score change from baseline ≤-3; Full Analysis Set with pruritus NRS ≥ 3% at baseline (FIL N=36, PBO N=36); NRI=non-responder imputation

58.3

22.2

0

10

20

30

40

50

60

70

80

90

100

change from baseline ≤-3FIL N=42 PBO N=40

**

PruritusPh2 EQUATOR study with filgotinib in PsA

21Pruritus responder=Pruritus NRS score change from baseline ≤-3; Full Analysis Set with pruritus NRS ≥ 3% at baseline (FIL N=36, PBO N=36); OC=observed case;

Pruritus, time to first response, OC Pruritus, response over time

LEI activity at Week 16Ph2 EQUATOR study with filgotinib in PsA

22

% responders

**: p<0.01

LEI = Leeds Enthesitis Index; FAS with baseline enthesitis (LEI >0); NRI=non-responder imputation

51.5

25.6

0

10

20

30

40

50

60

70

80

90

100

FIL N=33 PBO N=43

**

LEI=0, NRI

LEI activityPh2 EQUATOR study with filgotinib in PsA

23

23

LEI, time to first response, OC LEI, response over time

LEI = Leeds Enthesitis Index; FAS with baseline enthesitis (LEI >0); NRI=non-responder imputation

SafetyPh2 EQUATOR study with filgotinib in PsA

*1 patient died following pneumonia infection24

n (%) Filgotinib(N=65)

Placebo(N=66)

TE AE 37 (56.9) 39 (59.1)

Serious TE AE 1 (1.5) 1 (1.5)

Leading to temporary study drug interruption 5 (7.7) 8 (12.1)

Leading to permanent study drug discontinuation 1 (1.5) 0

Infections 14 (21.5) 14 (21.2)

All serious infections 1 (1.5)* 0

Opportunistic infections 0 0

Herpes zoster 1 (1.5) 0

Active tuberculosis 0 0

Pneumonia 1 (1.5)* 0

Malignancies, incl. lymphoma 0 0

Deep venous thrombosis, pulmonary embolism 0 0

Adjudicated Major Adverse Cardiac Events (MACE) 0 0

Death 1 (1.5)* 0

Safety - key hematology parametersPh2 EQUATOR study with filgotinib in PsA

25

200220240260280300

FIL PBO

Platelets, mean (109/L)

13

13.5

14

14.5

15

FIL PBO

Hemoglobin, mean (g/dL)

0

2

4

6

FIL PBO

Neutrophils, mean (109/L)

11.21.41.61.8

2

FIL PBO

Lymphocytes, mean (109/L)

150175200225250275300

FIL PBO

NK cells (/µL)

Baseline Week 16

FIL PBOGrade 2 3 (4.6%) -Grade 3-4 - -

FIL PBOGrade 2 3 (4.6%) 2 (3.0%)Grade 3 - 1 (1.5%)Grade 4 - -

FIL PBOWorstcase decrease <LLN 6 (9.2%) 1 (1.6%)Worstcase increase >ULN 1 (1.5%) -

Toxicity grades were defined by modified Common Terminology Criteria for Adverse Events (CTCAE) v4.03. Worst case CTCAE grades for each subject are reported

FIL PBOGrade 2-4 - -

FIL PBOGrade 2-4 - -

Safety - key chemistry parametersPh2 EQUATOR study with filgotinib in PsA

26Baseline Week 16

100

120

140

FIL PBO

Creatinine clearance, mean (mL/min)

0.6

0.7

0.8

0.9

FIL PBO

Creatinine, mean (mg/dL)

0

10

20

30

FIL PBO

AST, mean (U/L)

FIL PBOGrade 2 1 (1.5%) 1 (1.5%)

Grade 3-4 - -

FIL PBOGrade 2 7 (10.8) 3 (4.1)

Grade 3 1 (1.5%) -

Grade 4 - -

FIL PBOGrade 2 10 (15.4%) 4 (6.0%)

Grade 3-4 - -

Toxicity grades were defined by modified Common Terminology Criteria for Adverse Events (CTCAE) v4.03. Worst case CTCAE grades for each subject are reported

050

100150200250

FIL PBO

Total Cholesterol (mg/dL)

0255075

100125150

FIL PBO FIL PBO

LDL, mean (mg/dL)

3.53.73.94.14.34.5

FIL PBO

Total Cholesterol / HDL

FIL PBOGrade 2 4 (6.2%) 1 (1.6%)

Grade 3-4 - -HDL and LDL are not part of CTCAE grading system

ConclusionsPh2 EQUATOR study with filgotinib in PsA

♦ Selective JAK1 inhibition by filgotinib significantly improved signs and symptoms of PsAin patients with active disease vs placebo

– Primary and key secondary endpoints achieved

♦ Patients treated with filgotinib achieved ACR20 response earlier and responses over time appear to be more stable

– Patients on PBO had more occurrences of response being lost over time and fewer cases of regaining a lost response

– Similar trends were observed for other efficacy endpoints

♦ Safety profile of filgotinib after 16 weeks of treatment in line with previous reports, without new safety signals

♦ Positive proof-of-concept study with filgotinib in patients with active psoriatic arthritis

27http://dx.doi.org/10.1016/S0140-6736(18)32483-8

Acknowledgments

We extend our thanks to the patients, their families, and all participating investigators– Belgium: Leon M, Malaise M, Margaux J, Van den Bosch F– Bulgaria: Marinova N, Penev D, Rashkov R, Spasov Y, Stoilov R, Vladeva S, Velkova M– Czech Republic: Dokoupilova E, Hala T, Urbanova Z– Estonia: Raussi E, Tälli S, Valter I– Poland: Dudek A, Glowacka-Kulesz M, Gruszecka K, Jeka S, Miakisz M, Nowak N,

Rychlewska-Hanczewska A, Swierkocka K– Spain: Fernandez Nebro A, Gratacos Masmitja J, Mera Varela A, Navarro Sarabia F, Perez Venegas J,

Povedano Gomez J, Veiga Cabello R– Ukraine: Garmish O, Golovchenko O, Nadashkevych O, Shevchuk S, Smiyan S, Stanislavchuk M,

Trubina S, Tseluyko V, Turyanytsya S, Zhdan V

This study was funded by Gilead Sciences, Inc. and Galapagos NV

28