Improving the Lives of Patients with Liver Diseases

Effects on Pruritus and Sleep Disturbance in Patients with Primary Biliary Cholangitis (PBC) after 1 Year of Treatment

with Seladelpar, a Peroxisome Proliferator-Activated Receptor Delta Agonist: Results of an Open-label Phase 2 Study

Andreas E. Kremer, Marlyn Mayo, Christopher Bowlus, Guy Neff, Mark Swain, Michael Galambos, Aparna Goel, Palak Trivedi, Gideon Hirschfield, Richard Aspinall, Stuart Gordon, Brian Borg, Stephen A. Harrison, Paul J.

Thuluvath, David Jones, Yvonne Doerffel, Cynthia Levy, Carmen Stanca, David Sheridan, John Vierling, Mitchell Shiffman, Joseph Odin, Bruce Bacon, Tarek Hassanein, Douglas Thorburn, Christoph Berg, David Bernstein,

Aliya Gulamhusein, Charles Landis, Adam Peyton, Lynsey Corless, Peter Buggisch, Marcus-Alexander Woerns, Sandrin Bergheanu, Monika Varga, Yu Li, Ke Yang, Klara Dickinson, Pol Boudes, Charles A. McWherter,

Alexandra Steinberg, Yun-Jung Choi

June | 2020

Digestive Disease Week (DDW) 2020 Virtual Meeting 1

2Digestive Disease Week (DDW) 2020 Virtual Meeting

Disclosures

Consultant / Advisor: Beiersdorf, CymaBay, Elsevier, GSK, Guidepoint, Intercept, Janssen, MSD

Speaker: Abbvie, BMS, CMS, CymaBay, Eisai, Falk, Gilead, GSK, Intercept, Janssen, Lilly, MSD, Zambon


Phase 2 Open Label Study in PBCIncomplete response or intolerance to UDCA*

Seladelpar 5 mg (n = 49)

Seladelpar 10 mg (n = 52)

Seladelpar 5/10 mg

Entry Criteria: ALP ≥ 1.67 x ULN; ALT/AST ≤ 3 x ULN; Total Bilirubin ≤ 2 x ULN

Week 12†

* Seladelpar is an add-on to UDCA for patients with an inadequate response to UDCA in the prior 12 months (mITT population).† At week 12, a dose adjustment in the 5/10 mg group was made based on patient response and tolerability. ǂ Patients with ALP ≤ 1.67 x ULN, ≥ 15% drop in ALP from baseline and normal total bilirubin.

Long Term Extension

Option for Dose Adjustment

Primary Outcome: % Change in ALP from baseline

Secondary Outcomes: Composite responder rateǂ, ALP normalization, changes in liver, metabolic and inflammatory markers

1 Year


Effect of Seladelpar on Pruritus in Patients with PBC

Pruritus is a common symptom of PBC that diminishes quality of life Phase 2 PBC Study Design

− Patient reported outcomes were collected at clinic visit by recall methods Pruritus and Quality-of-Life Measures

− Visual Analog Scale (VAS)− 5-D Itch− PBC-40


Demographic and Baseline Characteristics of PBC Patients

mITT Population Seladelpar 5/10 mg

Seladelpar 10 mg

N 49 52Female, n (%) 48 (98%) 48 (92%)Age, years 58 (8) 58 (10)BMI, kg/m2 26 (5) 28 (5)White, n (%) 47 (96%) 47 (90%)Duration of PBC, years 10 (7) 10 (6)History of Pruritus, n (%) 36 (73%) 36 (69%)UDCA Dose, mg/kg/day 15 (3) 15 (4)UDCA intolerant, n (%) 4 (8%) 3 (6%)ALP ULN: 116 U/L 353 (193) 301 (138)ALT ULN: 41 U/L 46 (25) 46 (21)Total bilirubin ULN: 1.1 mg/dL 0.76 (0.36) 0.83 (0.33)GGT ULN: 38 U/L 244 (150) 239 (196)Mean (SD)


Pruritus VASBaseline vs. 1 Year

0102030405060708090

100

VAS

Seladelpar Seladelpar 5/10 mg 10 mg

Baseline 1 Year Baseline 1 Year


Effect of Seladelpar Treatment on Pruritus after 1 Year By severity of pruritus at baseline

5/10 mg 10 mg 5/10 mg 10 mg 5/10 mg 10 mg 5/10 mg 10 mgn: 7 11 22 22 9 11 3 4

Baseline VAS: VAS = 0 0 < VAS < 40 40 ≤ VAS < 70 70 ≤ VAS ≤ 100 (mm)

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100

Prop

ortio

n of

Pat

ient

s (%

)

ImprovedSameWorsened

VAS Change by 20 mm at 1 YearNo pruritus Mild Moderate Severe/

Very Severe


Correlations between Changes in Pruritus Measures at 1 YearVAS vs. Total 5-D Itch, PBC-40 Itch or Fatigue

∆ Total 5-D Itch ∆ PBC-40 Itch ∆ PBC-40 Fatigue

∆ VA

S

r = 0.65p < 0.0001

r = 0.61p < 0.0001

r = 0.40p = 0.0001

5/10 mg 10 mg


5-D Itch: DurationHow many hours a day have you been itching?

5-D Itch: Duration5/10 mg 10 mg

Baseline At 1 Year Baseline At 1 Year

Baseline Total 1 2 3 4 5 Total 1 2 3 4 5

1: Less than 6 hrs/day 30 28 2 0 0 0 38 36 2 0 0 02: 6-12 hrs/day 7 3 3 1 0 0 6 6 0 0 0 03: 12-18 hrs/day 1 1 0 0 0 0 2 1 1 0 0 04: 18-23 hrs/day 0 0 0 0 0 0 0 0 0 0 0 05: All day 2 2 0 0 0 0 1 1 0 0 0 0

Total 40 34 5 1 0 0 47 44 3 0 0 00102030405060708090

100

Prop

ortio

n of

Pat

ient

s (%

)

BL 1 Yr BL 1 Yr

5/10 mg 10 mg


5-D Itch: DegreeIntensity of itching

5-D Itch: Degree5/10 mg 10 mg



1: Not present 15 12 3 0 0 0 17 14 2 1 0 0

2: Mild 13 4 7 2 0 0 13 4 9 0 0 0

3: Moderate 10 3 2 5 0 0 12 5 5 2 0 0

4: Severe 3 0 2 1 0 0 5 0 2 2 1 0

5: Unbearable 0 0 0 0 0 0 5 0 0 0 0 0

Total 41 19 14 8 0 0 47 23 18 5 1 00102030405060708090

100

Prop

ortio

n of

Pat

ient

s (%

)

BL 1 Yr BL 1 Yr

5/10 mg 10 mg


5-D Itch: DirectionHas itching gotten better or worse?

5-D Itch: Direction5/10 mg 10 mg



1: Completely resolved 8 7 0 0 1 0 9 7 1 0 1 02: Much better, but

still present 9 4 2 0 3 0 4 2 1 1 0 03: Little bit better, but

still present 4 2 1 0 1 0 1 1 0 0 0 0

4: Unchanged 16 2 6 0 6 2 31 7 8 3 13 0

5: Getting worse 2 1 0 0 1 0 2 0 2 0 0 0

Total 39 16 9 0 12 2 47 17 12 4 14 00102030405060708090

100

Prop

ortio

n of

Pat

ient

s (%

)

BL 1 Yr BL 1 Yr

5/10 mg 10 mg


5-D Itch: DisabilityImpact of itching on the activities

5-D Itch: Disability with Highest Score

5/10 mg 10 mgBaseline At 1 Year Baseline At 1 Year


0: N/A 1 1 0 0 0 0 0 0 0 0 0 01: Never affects 15 14 1 0 0 0 20 18 1 1 0 02: Rarely affects 8 6 2 0 0 0 6 3 3 0 0 03: Occasionally affects 9 3 4 0 2 0 8 3 3 2 0 04: Frequently affects 3 1 1 0 1 0 9 3 1 3 2 05: Always affects 5 0 3 1 1 0 4 2 0 2 0 0

Total 41 25 11 1 4 0 47 29 8 8 2 0

Activities: Sleep, Leisure/Social, Housework/Errands, Work/School

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100

Prop

ortio

n of

Pat

ient

s (%

)

BL 1 Yr BL 1 Yr

5/10 mg 10 mg


5-D Itch: Distribution of Itching LocationsPresentation of itching body parts

Number of Itch Locations Per Patient

Median 5/10 mg 10 mg

Baseline 3 5

1 Year 2 1

0 5 10 15 20 25 30

GroinChest

ButtocksFace

Tops of Hands/FingersPoints of Contact w/ Clothing

ThighsSoles

Lower legsPalms

AbdomenTops of Feet/Toes

ForearmsUpper ArmsHead/Scalp

Back

5/10 mg

Number of Patients0 5 10 15 20 25 30

10 mg

Number of Patients

Day 11 Year

Day 11 Year


5-D Itch: Impact of Itching on Sleep

5-D Itch: Sleep5/10 mg 10 mg



1: Never affects sleep 19 17 2 0 0 0 24 21 3 0 0 02: Occasionally delays falling

asleep 10 7 3 0 0 0 8 5 3 0 0 03: Frequently delays falling

asleep 7 3 3 1 0 0 2 0 2 0 0 04: Delays falling asleep andoccasionally wakes me up at night 2 1 1 0 0 0 9 4 2 1 2 0

5: Delays falling asleep andfrequently wakes me up at night 2 0 1 0 1 0 4 2 0 2 0 0

Total 40 28 10 1 1 0 47 32 10 3 2 00102030405060708090

100

Prop

ortio

n of

Pat

ient

s (%

)

BL 1 Yr BL 1 Yr

5/10 mg 10 mg


PBC-40: Itch

Q8. Itch disturbed my sleep Q9. I scratched so much Q10. I felt embarrassed because I made my skin raw of the itching

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100

Prop

ortio

n of

Pat

ient

s (%

)

BL 1 Yr BL 1 Yr

5/10 mg 10 mg

0102030405060708090

100

Prop

ortio

n of

Pat

ient

s (%

)

BL 1 Yr BL 1 Yr

5/10 mg 10 mg

0102030405060708090

100

Prop

ortio

n of

Pat

ient

s (%

)

BL 1 Yr BL 1 Yr

5/10 mg 10 mg

Did not apply/no itchNeverRarelySometimesMost of the timeAlways


PBC-40: Fatigue

Q13. Fatigue interfered with my daily routine

Q17. Fatigue just suddenly hit me

Q18. PBC drained every ounce of energy out of me

0102030405060708090

100

Prop

ortio

n of

Pat

ient

s (%

)

BL 1 Yr BL 1 Yr

5/10 mg 10 mg

0102030405060708090

100

Prop

ortio

n of

Pat

ient

s (%

)

BL 1 Yr BL 1 Yr

5/10 mg 10 mg

0102030405060708090

100

Prop

ortio

n of

Pat

ient

s (%

)

BL 1 Yr BL 1 Yr

5/10 mg 10 mg

NeverRarelySometimesMost of the timeAlways


Conclusions

Seladelpar treatment for 1-year reduced pruritus burden in PBC− Most patients with baseline VAS ≥ 40 mm improved by ≥ 20 mm− Correlated improvements: VAS, 5D-Itch and PBC-40 Itch− Sleep disturbance reduced by 5D-Itch and PBC-40

ENHANCE Placebo-Controlled Results (Fall 2020)− Placebo, 5 and 10 mg− Numeric Rating Scale (NRS) e-Diary− Quality-of-life (daily activities, fatigue and more)

Seladelpar symptom improvement supports further evaluation in PBC

Improving the Lives of Patients with Liver Diseases

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