get to know jakafi (ruxolitinib)

Get to Know Jakafi® (ruxolitinib)

For advanced practice providers who manage adults with polycythemia

vera who have an inadequate response to hydroxyurea

BEGIN • Jakati®G

ruxolitinib (tablets) 5mg • 10mg • 15mg • 20mg , 25mg

Overview

• Get to Know Jakafi® (ruxolitinib) is a self-guided

learning module developed specifically for advanced

practice providers (APPs) who manage patients with

polycythemia vera (PV)

• The module provides information about clinical

experience with Jakafi in adults with PV who have

had an inadequate response to or are intolerant of HU

• Important Safety Information is reviewed within this module

– Select Safety Information: Treatment with Jakafi can cause thrombocytopenia, anemia and

neutropenia. Perform a pre-treatment complete blood count (CBC) and monitor CBCs every

2 to 4 weeks until doses are stabilized, and then as clinically indicated. In patients with cytopenias,

consider dose reductions, temporarily interrupting Jakafi or transfusions, as clinically indicated.

Please see Important Safety Information for related and other risk information and Full

Prescribing Information available at https://www.jakafi.com/pdf/prescribing-information.pdf

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•

Jakafi-C ruxolitinib (tablets)

5mg • 10mg • 15mg • 20mg • 25mg

https://www.jakafi.com/pdf/prescribing-information.pdf

How to Use This Module

• This is a self-guided learning module

that allows you to:

– Explore information and data sets in detail

– Consider ways to apply the information to

clinical practice

• Each slide contains:

– Core clinical information

– Clickable prompts with additional insights

that can be expanded and collapsed

– Questions to consider about your own

practice

Important: The slides in this module are designed to be

viewed in the sequence presented. The clickable prompts on

each slide all need to be opened in numeric order before

proceeding to the next slide using the “Next” button located in

the upper right corner.

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3

The Presence of Certain Factors May Be a Potential Indication for Change in Cytoreductive Therapy

ELN, European LeukemiaNet; FDA, Food and Drug Administration; HU, hydroxyurea; IWG-MRT, International Working Group-Myeloproliferative Neoplasms Research and Treatment;

NCCN, National Comprehensive Cancer Network; PV, polycythemia vera.

References: 1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Myeloproliferative Neoplasms V.2.2021.

© National Comprehensive Cancer Network, Inc 2021. All rights reserved. Accessed August 18, 2021. To view the most recent and complete version of the guideline, go online to NCCN.org.

NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 2. Barbui T et al.

J Clin Oncol. 2011;29(6):761-770.

Actively monitor patient response and

signs/symptoms of disease progression

Assessments should be made

• Every 3 to 6 months or more frequently as

clinically indicated

• Per IWG-MRT and ELN Response Criteria

Monitor for new thrombosis or bleeding

The presence of any one of these factors may

warrant a change in cytoreductive therapy

• Intolerance or resistance to HU2 or peginterferon alfa-2a

• Disease-related symptoms

• New thrombosis or disease-related major bleeding

• Progressive thrombocytosis and/or leukocytosis

• Frequent and/or persistent need for phlebotomy,

but with poor tolerance of phlebotomy

• Splenomegaly

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Recommendations for Patients With PV on Cytoreductive Therapy1

1

2

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• - •

• Jakafi O

ruxolrtinib ltabletsl


5mg • 10mg • 15mg • 20mg • 25mg

Introduction

Clinical characteristics of advanced PV

NEXT •

Jakati®G ruxolitinib (tablets)

5mg • 10mg • 15mg • 20mg , 25mg

PV Is a Hematologic Malignancy That May Become Advanced in a Subset of Patients1-6

• Clinical characteristics of advanced PV, despite treatment with HU at the maximum tolerated

dose and phlebotomy, include1,7-9:

Hct, hematocrit; HU, hydroxyurea; PV, polycythemia vera; WBC, white blood cell.

References: 1. Barosi G et al. Br J Haematol. 2010;148(6):961-963. 2. Parasuraman S et al. Exp Hematol Oncol. 2016;5:3. 3. Mascarenhas J. Clin Lymphoma Myeloma Leuk.

2016;16(suppl):S124-S129. 4. Rumi E et al. Blood. 2017;129(6):680-692. 5. Michiels JJ et al. World J Hematol. 2013;2(3):71-88. 6. Michiels JJ. World J Crit Care Med. 2015;4(3):230-239.

7. Marchioli R et al. N Engl J Med. 2013;368(1):22-33. 8. Barbui T et al. Blood. 2015;126(4):560-561. 9. Emanuel R et al. Clin Oncol. 2012;30(33):4098-4103.

Hct

≥45%

Disease-related

SYMPTOMSWBCCOUNT

>11 109/L

PLUS OR

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5

•

'= ,~

'-


5mg • 10mg • 15mg • 20mg • 25mg


6



Assessments should be made:













• Splenomegaly

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Recommendations for Patients With PV on Cytoreductive Therapy1

1

2

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ELN, European LeukemiaNet; HU, hydroxyurea; IWG-MRT, International Working Group-Myeloproliferative Neoplasms Research and Treatment;





J Clin Oncol. 2011;29(6):761-770.

•


5mg • 10mg • 15mg • 20mg • 25mg






J Clin Oncol. 2011;29(6):761-770.

















• Splenomegaly

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Recommendations for Patients with PV on Cytoreductive Therapy1

Note that these potential indicators for change of

therapy encompass the clinical characteristics of

advanced PV:

• Elevated Hct potentially due to intolerance or resistance to

HU and/or frequent/persistent need for phlebotomy

• Elevated WBC counts


1

X






J Clin Oncol. 2011;29(6):761-770.

















• Splenomegaly

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Recommendations for Patients with PV on Cytoreductive Therapy1

• Jakafi® (ruxolitinib) is FDA approved for treatment

of PV in adults who have had an inadequate response to or are

intolerant of HU1

• The phase 3 RESPONSE study defined inadequate response to

include the maximum tolerated dose of HU, not just the ELN

criteria of 2 g/d, after 3 months2,3

• RESPONSE was an open-label trial and, therefore, not designed

to evaluate a difference in symptoms1

• The clinical effect of Jakafi on thrombosis has not been

established

FDA, Food and Drug Administration.

References: 1. Jakafi Prescribing Information. Wilmington, DE: Incyte Corporation.

2. Vannucchi AM et al. N Engl J Med. 2015;372(5):426-435. 3. Barbui T et al. J Clin Oncol.

2011;29(6):761-770.

2

X

NCCN Guidelines® for Myeloproliferative Neoplasms

FDA, Food and Drug Administration; NCCN, National Comprehensive Cancer Network; PV, polycythemia vera.

References: 1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Myeloproliferative Neoplasms V.2.2021. © National

Comprehensive Cancer Network, Inc 2021. All rights reserved. Accessed August 18, 2021. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN

makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 2. Jakafi Prescribing Information.

Wilmington, DE: Incyte Corporation.

NCCN Guidelines recommend ruxolitinib as a treatment option

for patients with PV who have had an inadequate response

to or are intolerant of cytoreductive therapy1

Ruxolitinib (Jakafi®) is the first and only FDA-approved

therapy for treatment of PV in adults who have had an

inadequate response to or are intolerant of hydroxyurea2

7

1

NEXT •

JakatrC ruxolitinib (tablets)

5mg • 10mg , 15mg , 20mg , 25mg

FDA, Food and Drug Administration; NCCN, National Comprehensive Cancer Network; PV, polycythemia vera.

References: 1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Myeloproliferative Neoplasms V.2.2021. © National

Comprehensive Cancer Network, Inc 2021. All rights reserved. Accessed August 18, 2021. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN

makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 2. Jakafi Prescribing Information.

Wilmington, DE: Incyte Corporation.

NCCN Guidelines® for Myeloproliferative Neoplasms

NCCN Guidelines recommend ruxolitinib as a treatment option

for patients with PV who have had an inadequate response

to or are intolerant of cytoreductive therapy1

Ruxolitinib (Jakafi®) is the first and only FDA-approved

therapy for treatment of PV in adults who have had an

inadequate response to or are intolerant of hydroxyurea2

Initial results from the Jakafi

registrational RESPONSE trial were first

published in Vannucchi AM, Kiladjian

JJ, Greisshammer M, et al. Ruxolitinib

versus standard therapy for the

treatment of polycythemia vera. N Engl

J Med. 2015;372(5):426-435.

1

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RESPONSE Trial

Ruxolitinib vs standard therapy in phlebotomy-dependent PV patients

with splenomegaly who were resistant or intolerant to HU

NEXT •

JakatrS ruxolitinib (tablets)

5mg • 10mg • 15mg , 20mg , 25mg

Jakafi

10 mg twice daily

(n = 110)

Crossover to

Jakafi

Week 32

Primary Analysisc

Week 80 Week 256

Final Planned

Analysis

BATHU 60% Obs 15%IFN 12%

Other 13%>1 agent 5%

(n = 112)

• Resistance to or

intolerance of HUa

• Phlebotomy requirementb

• Splenomegaly with CT- or

MRI-confirmed volume

Prerandomization

(day −28 to day −1)

Hct between

40% and 45%

Hct Control Period

Ra

nd

om

ize

d 1

:1

RESPONSE Trial Design

9

BAT, best available therapy; CT, computed tomography; ELN, European LeukemiaNet; Hct, hematocrit; HU, hydroxyurea; IFN, interferon; MRI, magnetic resonance imaging;

Obs, observation.a Based on modified ELN criteria.2,6

b Phlebotomy eligibility requirement: Patients required at least 2 phlebotomies within the 24 weeks before screening (the most distant and the most recent phlebotomies must have been at

least 4 weeks apart) and at least 1 phlebotomy within the 16 weeks before screening. Patients also could have met the criteria if they required a phlebotomy within the 16 weeks before

screening and had an Hct level >45% at screening.2

c The composite primary endpoint was defined as Hct control without phlebotomy eligibility and a ≥35% spleen volume reduction as measured by CT or MRI. To achieve the Hct control

endpoint, patients could not become eligible for phlebotomy between weeks 8 and 32. Phlebotomy eligibility was defined as Hct >45% that is ≥3 percentage points higher than baseline

or Hct >48% (lower value).1,2

References: 1. Jakafi Prescribing Information. Wilmington, DE: Incyte Corporation. 2. Vannucchi AM et al. N Engl J Med. 2015;372(5):426-435. 3. Kiladjian JJ et al. Lancet Haematol.

2020;7(3):E226-E237. 4. Data on file. Incyte Corporation. Wilmington, DE. 5. Harrison C et al. Br J Haematol. 2018;182(2):279-284. 6. Barosi G et al. Br J Haematol. 2009;148(6):961-963.

RESPONSE Trial Design1-5

of patients in the Jakafi arm completed 5 YEARS OF ON-STUDY TREATMENT366%

3

1

2

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•I


5mg • 10mg • 15mg • 20mg • 25mg

Jakafi

10 mg twice daily

(n = 110)

Crossover to

Jakafi

Week 32

Primary Analysisc

Week 80 Week 256

Final Planned

Analysis



(n = 112)


intolerance of HUa




Prerandomization


Hct between

40% and 45%

Hct Control Period

Ra

nd

om

ize

d 1

:1














Jakafi was assessed vs standard therapy in

phlebotomy-dependent PV patients with

splenomegaly who were resistant or intolerant

to HU.

RESPONSE was a randomized, open-label, active-

controlled phase 3 trial comparing Jakafi with best

available therapy (BAT) in 222 patients.

BAT in the trial was defined as single-agent therapy

chosen at the treating physician’s discretion. BAT

included hydroxyurea, interferon or pegylated

interferon, pipobroman, anagrelide, immunomodulators

such as lenalidomide or thalidomide, or no medication.

PV, polycythemia vera.

Reference: Jakafi Prescribing Information. Wilmington, DE: Incyte Corporation.

1

X

•

Jakafi

10 mg twice daily

(n = 110)

Crossover to

Jakafi

Week 32

Primary Analysisc

Week 80 Week 256

Final Planned

Analysis



(n = 112)


intolerance of HUa




Prerandomization


Hct between

40% and 45%

Hct Control Period

Ra

nd

om

ize

d 1

:1














Remember: NCCN Guidelines list a number of factors

that could indicate the need for a change in

cytoreductive therapy.1

Eligibility criteria in the RESPONSE trial touched on

3 of these factors2:

• Intolerance or resistance to HU or peginterferon

alfa-2a



• Splenomegaly

Reference: 1. Referenced with permission from the NCCN Clinical Practice

Guidelines in Oncology (NCCN Guidelines®) for Myeloproliferative Neoplasms

V.2.2021. © National Comprehensive Cancer Network, Inc 2021. All rights

reserved. Accessed August 18, 2021. To view the most recent and complete

version of the guideline, go online to NCCN.org. NCCN makes no warranties of any

kind whatsoever regarding their content, use or application and disclaims any

responsibility for their application or use in any way. 2. Jakafi Prescribing

Information. Wilmington, DE: Incyte Corporation.

2

X

•I

•

Jakafi

10 mg twice daily

(n = 110)

Crossover to

Jakafi

Week 32

Primary Analysisc

Week 80 Week 256

Final Planned

Analysis



(n = 112)


intolerance of HUa




Prerandomization


Hct between

40% and 45%

Hct Control Period

Ra

nd

om

ize

d 1

:1














Long-term follow up from the RESPONSE trial

found that 66% of patients in the Jakafi arm

completed 5 years of on-treatment study.

The study authors concluded that Jakafi is a

safe and effective long-term treatment option

for patients with PV who are resistant to or

intolerant of HU.

Reference: Kiladjian JJ et al. Lancet Haematol. 2020;7(3):E226-E237.

3

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•

RESPONSE Baseline Demographics and Disease Characteristics

10

Values shown are mean (SD) unless otherwise indicated.

Hct, hematocrit; HU, hydroxyurea; SD, standard deviation; WBC, white blood cell.a Following Hct control period prior to randomization.

References: 1. Vannucchi AM et al. N Engl J Med. 2015;372(5):426-435. 2. Data on file. Incyte Corporation. Wilmington, DE.

NEXT

Characteristic1

Jakafi

(n = 110)

Best Available Therapy

(n = 112)

Age in years, median (range) 62 (34-90) 60 (33-84)

Men, % 60 71

HU resistance/intolerance, %

Resistance

Intolerance

46.4

53.6

45.5

54.5

HU dose at baseline, median (range), g/day2

HU resistant

HU intolerant

1.0 (0.3-2.5), n = 49

1.0 (0.1-2.5), n = 28

1.25 (0.5-2.2), n = 48

1.5 (0.1-2.0), n = 25

History of prior thromboembolic event, % 35.5 29.5

JAK2V617F-positive, % 94.5 95.5

Hct, %a 43.6 (2.2) 43.9 (2.2)

WBC 109/L 17.6 (9.6) 19.0 (12.2)

Platelets 109/L 485 (323) 499 (319)

≥3 phlebotomies in prior 24 weeks, %2 30.9 42.0

Spleen length, median (range), cm 7 (0-24) 7 (0-25)

Spleen volume, median (range), cm3 1195 (396-4631) 1322 (254-5147)

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5mg • 10mg • 15mg • 20mg • 25mg



Hct, hematocrit; HU, hydroxyurea; SD, standard deviation; WBC, white blood cell.a Following Hct control period prior to randomization.


Characteristic1

Jakafi

(n = 110)


(n = 112)


Men, % 60 71


Resistance

Intolerance

46.4

53.6

45.5

54.5


HU resistant

HU intolerant

1.0 (0.3-2.5), n = 49

1.0 (0.1-2.5), n = 28

1.25 (0.5-2.2), n = 48

1.5 (0.1-2.0), n = 25



Hct, %a 43.6 (2.2) 43.9 (2.2)

WBC 109/L 17.6 (9.6) 19.0 (12.2)

Platelets 109/L 485 (323) 499 (319)




HU resistance was defined as a dose ≥2 g/day or a

maximum tolerated dose <2 g/day resulting

in at least 1 of the following:

• Need for phlebotomy to maintain Hct <45%

• Platelets >400 × 109/L and WBC >10 × 109/L

• Failure to reduce splenomegaly extending >10 cm below the costal

margin by >50%, as measured by palpation

HU intolerance was defined as:

• ANC <1.0 × 109/L, platelets <100 × 109/L, or Hb <10 g/dL at the

lowest dose of HU required to achieve a response

• Presence of leg ulcers or other unacceptable HU-related

nonhematologic toxicities at any dose of HU

ANC, absolute neutrophil count; Hb, hemoglobin.

Reference: Vannucchi AM et al. N Engl J Med. 2015;372(5):426-435.

1

X



ANC, absolute neutrophil count; Hb, hemoglobin; Hct, hematocrit; HU, hydroxyurea; SD, standard deviation; WBC, white blood cell.a Following Hct control period prior to randomization.


Characteristic1

Jakafi

(n = 110)


(n = 112)


Men, % 60 71


Resistance

Intolerance

46.4

53.6

45.5

54.5


HU resistant

HU intolerant

1.0 (0.3-2.5), n = 49

1.0 (0.1-2.5), n = 28

1.25 (0.5-2.2), n = 48

1.5 (0.1-2.0), n = 25



Hct, %a 43.6 (2.2) 43.9 (2.2)

WBC 109/L 17.6 (9.6) 19.0 (12.2)

Platelets 109/L 485 (323) 499 (319)




1

Remember: The clinical characteristics of advanced PV include1-3:

• Hct ≥45% plus

• WBC count >11 109/L or


The RESPONSE trial evaluated a number of clinical endpoints,

but this training module will focus on the management of these 3

disease characteristics.

The table shows mean Hct and WBC counts at baseline among

patients in the trial. Note that patients with Hct <40% or >45%

entered a Hct control period prior to randomization.

References: 1. Barbui T et al. Blood. 2015;126(4):560-561. 2. Marchioli R et al. N Engl J Med.

2013;368(1):22-33. 3. Emanuel R et al. Clin Oncol. 2012;30(33):4098-4103.

Hct, %a 43.6 (2.2) 43.9 (2.2)

WBC 109/L 17.6 (9.6) 19.0 (12.2)X

2

0

20

40

60

80

100

Pro

ba

bilit

y (

%)

Duration of Response (Weeks)

No. of responders/events/censor: 25/6/19

Kaplan-Meier median: not reached

Censoring timesJakafi

0

6 18 30 42 54 66 78 90 102 114 126 138 150 162 174 186 198 210 222

12 24 36 48 60 72 84 96 108 120 132 144 156 168 180 192 204 216 228

EventsAt risk 25

0

25

0

25

0

25

0

25

0

25

0

24

1

22

2

22

2

22

2

22

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0

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Reproduced from Lancet Haematol. Vol. 7 number 3. Kiladjian J-J et al. Long-term efficacy and safety of ruxolitinib versus best available therapy in polycythaemia

vera (RESPONSE): 5-year follow up of a phase 3 study. Pages e226-e237. Copyright 2020, with permission from Elsevier.

23%(25/110) of patients

receiving Jakafi achieved

Hct control and ≥35%

spleen volume reduction at

week 32 vs <1% (1/112) of

patients receiving BAT (P < 0.0001)1b

RESPONSE Composite Primary Endpoint1a

BAT, best avilable therapy; CI, confidence interval; CT, computed tomography; Hct, hematocrit; MRI, magnetic resonance imaging.a The composite primary endpoint was defined as Hct control without phlebotomy eligibility and a ≥35% spleen volume reduction as measured by CT or MRI. Phlebotomy eligibility was defined as Hct >45%

that is ≥3 percentage points higher than baseline or Hct >48% (lower value).1,2

b Jakafi 95% CI, 15%-32%; BAT 95% CI, 0%-5%.1

c Analysis was conducted in week 32 primary responders, beginning at week 32. The median duration of primary response was not reached. Progression was defined as: the first of 2 consecutive Hct

assessments that confirmed phlebotomy eligibility, a spleen volume that was reduced by <35% from the baseline AND that was 25% increased at the time of the best documented spleen volume response,

death, or development of myelofibrosis or acute leukemia.3

References: 1. Jakafi Prescribing Information. Wilmington, DE: Incyte Corporation. 2. Kiladjian JJ et al. Lancet Haematol. 2020;7(3):E226-E237. 3. Data on file. Incyte Corporation. Wilmington, DE.

Kaplan-Meier Estimate: Durability of Primary Response at 5 Years

(95% CI: 0.51, 0.88)

RESPONSE Trial

Probability of Maintaining the Primary Response at 5 Years2c74%

1

3

2

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5mg • 10mg • 15mg • 20mg • 25mg



b Jakafi 95% CI, 15%-32%; BAT 95% CI, 0%-5%.1





0

20

40

60

80

100

Pro

ba

bilit

y (

%)





0

6 18 30 42 54 66 78 90 102 114 126 138 150 162 174 186 198 210 222

12 24 36 48 60 72 84 96 108 120 132 144 156 168 180 192 204 216 228

EventsAt risk 25

0

25

0

25

0

25

0

25

0

25

0

24

1

22

2

22

2

22

2

22

2

22

2

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22

2

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11

6

11

6

9

6

0

6







week 32 vs <1% (1/112) of

patients receiving BAT(P < 0.0001)1b



(95% CI: 0.51, 0.88)

RESPONSE Trial


z

The study primary endpoint

accounted for Hct control and

spleen volume reduction.

The composite primary endpoint in the

RESPONSE trial was defined as both

Hct control without phlebotomy

eligibility and a ≥35% spleen volume

reduction as measured by CT or MRI.

To achieve the Hct control endpoint,

patients could not become eligible for

phlebotomy between weeks 8 and 32

of the trial.

? How is Hct control defined at your

practice? How important is it to

achieve Hct control without relying

on phlebotomy?

Reference: Jakafi Prescribing Information. Wilmington, DE:

Incyte Corporation.X

1

? . TT rrrrTTTTTTTTrTTTTTTTT



b Jakafi 95% CI, 15%-32%; BAT 95% CI, 0%-5%.1





0

20

40

60

80

100

Pro

ba

bilit

y (

%)





0

6 18 30 42 54 66 78 90 102 114 126 138 150 162 174 186 198 210 222

12 24 36 48 60 72 84 96 108 120 132 144 156 168 180 192 204 216 228

EventsAt risk 25

0

25

0

25

0

25

0

25

0

25

0

24

1

22

2

22

2

22

2

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11

6

11

6

9

6

0

6







week 32 vs <1% (1/112) of

patients receiving BAT (P < 0.0001)1b



(95% CI: 0.51, 0.88)

RESPONSE Trial


BAT in the trial included HU (60%),

interferon/pegylated interferon (12%), anagrelide (7%),

pipobroman (2%), lenalidomide/thalidomide (5%), and

observation (15%).

HU, hydroxyurea.

Reference: Jakafi Prescribing Information. Wilmington, DE: Incyte Corporation.X

2

rrrrrrr TTrrrrrrr TT rrT TT TTT TT rrT TT TTT r

BAT, best avilable therapy; CI, confidence interval; CT, computed tomography; Hct, hematocrit; HU, hydroxyurea; MRI, magnetic resonance imaging.a The composite primary endpoint was defined as Hct control without phlebotomy eligibility and a ≥35% spleen volume reduction as measured by CT or MRI. Phlebotomy eligibility was defined as Hct >45%


b Jakafi 95% CI, 15%-32%; BAT 95% CI, 0%-5%.1






0

20

40

60

80

100

Pro

ba

bilit

y (

%)





0

6 18 30 42 54 66 78 90 102 114 126 138 150 162 174 186 198 210 222

12 24 36 48 60 72 84 96 108 120 132 144 156 168 180 192 204 216 228

EventsAt risk 25

0

25

0

25

0

25

0

25

0

25

0

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5

17

5

17

5

17

5

16

6

16

6

16

6

11

6

11

6

9

6

0

6







week 32 vs <1% (1/112) of

patients receiving BATb

(P < 0.0001)1c


(95% CI: 0.51, 0.88)

RESPONSE Trial

Probability of Maintaining the Primary Response at 5 Years2d74%


found patients on Jakafi who achieved the

primary response (n = 25) had a 74%

probability of maintaining that response at

5 years.


3

X

rrrrrrr TTrrrrrrr TT rrT TT TTT TT rrT TT TTT r

60%(66/110) of patients receiving

Jakafi achieved Hct controla

at week 32 vs 19% (21/112)

of patients receiving BAT1

RESPONSE Trial

Individual Component of Primary Endpoint

Jakafi Achieved a Higher Rate of Hct Control in the Absence of Phlebotomy Eligibility vs BAT1

12

BAT, best available therapy; CI, confidence interval; Hct, hematocrit; MF, myelofibrosis. a To achieve the Hct control endpoint, patients could not become eligible for phlebotomy between weeks 8 and 32. Phlebotomy eligibility was defined as Hct >45% that is 3 percentage points

higher than baseline or Hct >48% (lower value).1,3

b Analysis conducted in week 32 Hct control responders, beginning at week 32. Progression events for the evaluation of duration of absence of phlebotomy eligibil ity included first of 2

consecutive Hct assessments that confirms phlebotomy eligibility, death, or development of MF or acute leukemia.4

References: 1. Jakafi Prescribing Information. Wilmington, DE: Incyte Corporation. 2. Kiladjian JJ et al. Lancet Haematol. 2020;7(3):E226-E237. 3. Vannucchi AM et al. N Engl J Med.

2015;372(5):426-435. 4. Data on file. Incyte Corporation. Wilmington, DE.

Kaplan-Meier Estimate: Durability of Hct Control at 5 Years

(95% CI: 0.60, 0.83)

Probability of Maintaining Hct Control* at 5 Years2b

*Absence of phlebotomy eligibility.73%

Pro

ba

bilit

y (

%)


0

20

40

60

80

100

Reproduced from Lancet Haematol. Vol. 7 number 3. Kiladjian J-J et al. Long-term efficacy and safety of ruxolitinib versus best available therapy in polycythaemia vera

(RESPONSE): 5-year follow up of a phase 3 study. Pages e226-e237. Copyright 2020, with permission from Elsevier.

0

6

12

18

24

30

36

42

48

54

60

66

72

78

84

90

96

102

108

114

120

126

132

138

144

150

156

162

168

174

180

186

192

198

204

210

216

222

228

234

240

246

252

258

264


Kaplan-Meier median: N/A week


EventsAt risk 66

0

66

0

66

0

66

0

66

0

66

0

64

0

63

1

62

2

60

4

58

5

58

5

56

6

56

6

56

6

56

6

56

6

55

7

54

8

54

8

53

9

51

10

49

10

49

10

48

10

48

10

48

10

44

12

44

12

44

12

42

14

42

14

42

14

41

15

40

15

39

16

39

16

39

16

39

16

38

16

28

16

5

16

3

16

1

16

0

16

1

2

NEXT •

- I I I I'---.., ------......_ __ , •----·•-11

+


5mg • 10mg • 15mg • 20mg • 25mg







b Analysis conducted in week 32 Hct control responders, beginning at week 32. Progression events for the evaluation of duration of absence of phlebotomy eligibility included first of 2






at week 32 vs 19% (21/112)


RESPONSE Trial


(95% CI: 0.60, 0.83)

Pro

ba

bilit

y (

%)


0

20

40

60

80

100



0

6

12

18

24

30

36

42

48

54

60

66

72

78

84

90

96

102

108

114

120

126

132

138

144

150

156

162

168

174

180

186

192

198

204

210

216

222

228

234

240

246

252

258

264




EventsAt risk 66

0

66

0

66

0

66

0

66

0

66

0

64

0

63

1

62

2

60

4

58

5

58

5

56

6

56

6

56

6

56

6

56

6

55

7

54

8

54

8

53

9

51

10

49

10

49

10

48

10

48

10

48

10

44

12

44

12

44

12

42

14

42

14

42

14

41

15

40

15

39

16

39

16

39

16

39

16

38

16

28

16

5

16

3

16

1

16

0

16

Looking at just the Hct component of the composite

primary endpoint, 60% of patients on Jakafi achieved

Hct control at week 32.

Recall that 60% of patients in the BAT arm received HU.

HU, hydroxyurea.


X

1

T T T r T T T T T r T T T T T r T T T T







b Analysis conducted in week 32 Hct control responders, beginning at week 32. Progression events for the evaluation of duration of absence of phlebotomy eligibility included first of 2






at week 32 vs 19% (21/112)


RESPONSE Trial


(95% CI: 0.60, 0.83)

Pro

ba

bilit

y (

%)


0

20

40

60

80

100



0

6

12

18

24

30

36

42

48

54

60

66

72

78

84

90

96

102

108

114

120

126

132

138

144

150

156

162

168

174

180

186

192

198

204

210

216

222

228

234

240

246

252

258

264




EventsAt risk 66

0

66

0

66

0

66

0

66

0

66

0

64

0

63

1

62

2

60

4

58

5

58

5

56

6

56

6

56

6

56

6

56

6

55

7

54

8

54

8

53

9

51

10

49

10

49

10

48

10

48

10

48

10

44

12

44

12

44

12

42

14

42

14

42

14

41

15

40

15

39

16

39

16

39

16

39

16

38

16

28

16

5

16

3

16

1

16

0

16


found patients on Jakafi who achieved Hct control

(n = 66) had a 73% probability of maintaining that

response at 5 years.


2

X

T T r ~ T T T T r ~ T T T T T ~ T T T T T ~ T T T T T r T T T T T r T T T T T r T T T T

Secondary Endpoint

Jakafi Demonstrated Significantly Higher Rates of Complete Hematologic Remission (CHR) vs BAT1

13

BAT, best available therapy; CI, confidence interval; Hct, hematocrit. a Jakafi 95% CI, 16%-33%; BAT 95% CI, 4%-15%.1

b Analysis was conducted in week 32 CHR responders, beginning at week 32. Progression events for the evaluation of duration of CHR included first of 2 consecutive Hct

assessments to confirm phlebotomy eligibility, first of 2 contiguous visits where platelet count was >400 109/L or WBC count >10 109/L, death, or development of myelofibrosis

or acute leukemia.3

References: 1. Jakafi Prescribing Information. Wilmington, DE: Incyte Corporation. 2. Vannucchi AM et al. N Engl J Med. 2015;372(5):426-435. 3. Data on file. Incyte Corporation.

Wilmington, DE.

Kaplan-Meier Estimate: Durability of CHR at 5 Years

0

20

40

60

80

100

Pro

bab

ilit

y (

%)


0 12 24 36 48 60 72 84 96 108 120 132 144 156 168 180 192 204 216 228 240

6 18 30 42 54 66 78 90 102 114 126 138 150 162 174 186 198 210 222 234 246

26

0

24

0

24

0

24

0

24

0

24

0

24

0

21

3

21

3

18

4

18

4

17

5

17

5

16

6

16

6

16

6

16

6

16

6

15

7

15

7

15

7

15

7

14

8

13

8

13

8

13

8

13

8

13

8

13

8

12

9

11

10

11

10

11

10

11

10

11

10

10

10

10

10

10

10

9

10

6

10

0

10

At risk


No. of responders/events/censor: 26/10/16Kaplan-Meier median: not reached

Events



Probability of Maintaining CHR at 5 Years2b55%

(95% CI: 0.32, 0.73)



CHR at week 32 vs 8%

(9/112) of patients receiving

BAT (P = 0.0016)1a

RESPONSE Trial

1

2

NEXT •

~---,_ I L,

+


5mg • 10mg • 15mg • 20mg • 25mg


b Analysis was conducted in week 32 CHR responders, beginning at week 32. Progression events for the evaluation of duration of CHR included first of 2 consecutive Hct

assessments to confirm phlebotomy eligibility, first of 2 contiguous visits where platelet count was >400 109/L or WBC count >10 109/L, death, or development of myelofibrosis

or acute leukemia.3


Wilmington, DE





BAT (P = 0.0016)1a

RESPONSE Trial

Secondary Endpoint

Jakafi Demonstrated Significantly Higher Rates of Complete Hematologic Remission (CHR)a vs BAT1


0

20

40

60

80

100

Pro

bab

ilit

y (

%)


0 12 24 36 48 60 72 84 96 108 120 132 144 156 168 180 192 204 216 228 240

6 18 30 42 54 66 78 90 102 114 126 138 150 162 174 186 198 210 222 234 246

26

0

24

0

24

0

24

0

24

0

24

0

24

0

21

3

21

3

18

4

18

4

17

5

17

5

16

6

16

6

16

6

16

6

16

6

15

7

15

7

15

7

15

7

14

8

13

8

13

8

13

8

13

8

13

8

13

8

12

9

11

10

11

10

11

10

11

10

11

10

10

10

10

10

10

10

9

10

6

10

0

10

At risk



Events




(95% CI: 0.32, 0.73)

CHR was defined in the trial as:

Hct control (as defined in the primary

endpoint), platelet count ≤400 × 109/L,

and WBC count ≤10 × 109/L.1,2

WBC, white blood cell.

References: 1. Jakafi Prescribing Information. Wilmington,

DE: Incyte Corporation. 2. Vannucchi AM et al. N Engl J

Med. 2015;372(5):426-435.X

1

r r r r T T T T T T T T


b Analysis was conducted in week 32 CHR responders, beginning at week 32. Progression events for the evaluation of duration of CHR included first of two consecutive Hct

assessments that confirms phlebotomy eligibility, first of two contiguous visits where platelet count was >400 109/L or WBC count >10 109/L, death, or development of myelofibrosis

or acute leukemia.3


Wilmington, DE





BAT (P = 0.0016)1b

RESPONSE Trial

Secondary Endpoint

Jakafi Demonstrated Significantly Higher Rates of Complete Hematologic Remission (CHR)a vs BAT1


0

20

40

60

80

100

Pro

bab

ilit

y (

%)


0 12 24 36 48 60 72 84 96 108 120 132 144 156 168 180 192 204 216 228 240

6 18 30 42 54 66 78 90 102 114 126 138 150 162 174 186 198 210 222 234 246

26

0

24

0

24

0

24

0

24

0

24

0

24

0

21

3

21

3

18

4

18

4

17

5

17

5

16

6

16

6

16

6

16

6

16

6

15

7

15

7

15

7

15

7

14

8

13

8

13

8

13

8

13

8

13

8

13

8

12

9

11

10

11

10

11

10

11

10

11

10

10

10

10

10

10

10

9

10

6

10

0

10

At risk



Events




(95% CI: 0.32, 0.73)


found patients on Jakafi who achieved CHR

(n = 26) had a 55% probability of maintaining that

response at 5 years.


2

X

RESPONSE Individual Component of Complete Hematologic Remission: WBC Counts

Exploratory Analyses From the RESPONSE Trial

14

BAT, best available therapy; HU, hydroxyurea; SE, standard error; WBC, white blood cell.a In this particular analysis, data for patients treated with HU were included in the group of patients receiving BAT.2

b At baseline, 75.5% of patients (n = 83) receiving Jakafi and 71.4% of patients (n = 80) receiving BAT had WBC counts ≥11 × 109/L.2

References: 1. Vannucchi AM et al. N Engl J Med. 2015;372(5):426-435. 2. Harrison C et al. Br J Haematol. 2018;182(2):279-284.

From N Engl J Med. Vannucchi AM et al. Ruxolitinib versus standard therapy for the treatment of polycythemia vera. Volume

372. Pages 426-435. Copyright © 2015 Massachusetts Medical Society. Reproduced with permission from Massachusetts

Medical Society.

Reproduced with permission from Harrison CN et al. Comprehensive haematological control with ruxolitinib in patients with

polycythaemia vera resistant to or intolerant of hydroxycarbamide. Br J Haematol. 2018;182(2):279-284 & supplemental information.

Copyright © 2018 John Wiley & Sons, Ltd.

Mean Change From Baseline in WBC Counts For

Patient Subgroups With WBC Counts ≥11 109/L2a,bMean WBC Counts Over Time1

Jakafii

BAT

Standard error Jakafi

BAT

HU

1

NEXT

2

20

18 ..... ;;;- 16 ~

14 . e 12 :, 0 10 u u "' 3: e .. :i

12

No. of patients

Jakafi 110 106 BAT 111 107

16 20

Week

103

105

24

100

104

• •

28 32

96

87

! • •

•

-10 -+------------------------------------12 16 20 24 28 32

No. of patients Week

Jakafi 83 80 77 78 80 77 77 75 74 BAT 79 74 74 72 76 75 73 74 64 HU 46 43 42 41 44 43 42 42 34


5mg • 10mg • 15mg • 20mg • 25mg








Medical Society.






Jakafii

BAT


BAT

HU

1

The study assessed WBC counts as an

exploratory endpoint.

WBC counts ≤10 × 109/L were part of how CHR

was defined in the trial.1

Remember: One characteristic of advanced PV, in

addition to elevated Hct ≥45%, is WBC counts

>11 × 109/L despite treatment with HU at the

maximum tolerated dose and phlebotomy.2

? How do you manage patients with elevated

WBC counts at your practice?


References: 1. Vannucchi AM et al. N Engl J Med. 2015;372(5):426-435.

2. Barbui T et al. Blood. 2015;126(4):560-561.

1

X

. § 0

c., c., a, :::

C .. i

l\lo o p , n

?

Week Week








Medical Society.






Jakafii

BAT


BAT

HU

1

The study also assessed mean change from

baseline in WBC counts by patient subgroups

Change from baseline as assessed in patients with

WBC counts ≥11 × 109/L who received Jakafi, BAT,

and HU. Data for patients treated with HU were

also included in data for the group of patients

receiving BAT.

Reference: Harrison CN et al. Br J Haematol. 2018;182(2):279-284.

2

X

~ . § 0

c., c., a, ::: C .. i

l\lo o p , n Week No of patients Week

Patients Achieving a ≥50% Reduction in MPN-SAF Total Symptom Score at Week 321a

RESPONSE Exploratory Endpoint:Symptom Data

15

BAT, best available therapy; MPN-SAF, Myeloproliferative Neoplasm Symptom Assessment Form.a Patient-reported outcomes were assessed using the modified Myeloproliferative Neoplasm-Symptom Assessment Form (MPN-SAF) symptom diary. The MPN-SAF diary was

administered daily in an electronic diary format to score 14 disease-related symptoms on a scale of 0 (absent) to 10 (worst possible). At baseline, median Total Symptom Score was 23.4

(range, 0-106) in the group receiving Jakafi and 33.3 (range, 0-118) in the group receiving BAT. Patients with data at both baseline (value >0) and week 32 were included in this analysis.1,2


49%

64%

37%

62%

5%11% 13%

17%

0

20

40

60

80

All 14 Symptomson MPN-SAF

Cytokine Hyperviscosity Splenomegaly

Pa

tie

nts

Wit

h ≥

50

% R

ed

uc

tio

n

in S

ym

pto

m S

co

re (

%)

Symptom Clusters

(36/74)

(4/81)

(47/74)

(10/80)

(26/71)

(9/80)

(39/63)

(12/71)

Jakafi

BAT

From N Engl J Med. Vannucchi AM et al. Ruxolitinib versus standard therapy for the treatment of polycythemia vera. Volume 372.Pages 426-435. Copyright © 2015 Massachusetts Medical Society. Reproduced with permission from Massachusetts Medical Society.

1

NEXT

• •

•


5mg • 10mg • 15mg • 20mg • 25mg

BAT, best available therapy; MPN-SAF, Myeloproliferative Neoplasm Symptom Assessment Form.a Patient-reported outcomes were assessed using the modified Myeloproliferative Neoplasm-Symptom Assessment Form (MPN-SAF) symptom diary. The MPN-SAF diary was

administered daily in an electronic diary format to score 14 disease-related symptoms on a scale of 0 (absent) to 10 (worst possible). At baseline, median Total Symptom Score was 23.4

(range, 0-106) in the group receiving Jakafi and 33.3 (range, 0-118) in the group receiving BAT. Patients with data at both baseline (value >0) and week 32 were included in this analysis.1,2


RESPONSE Exploratory Endpoint:Symptom Data

49%

64%

37%

62%

5%11% 13%

17%

0

20

40

60

80

All 14 Symptomson MPN-SAF

Cytokine Hyperviscosity Splenomegaly

Pa

tie

nts

Wit

h ≥

50

% R

ed

uc

tio

n

in S

ym

pto

m S

co

re (

%)

Symptom Clusters

(36/74)

(4/81)

(47/74)

(10/80)

(26/71)

(9/80)

(39/63)

(12/71)

Jakafi

BAT

From N Engl J Med. Vannucchi AM et al. Ruxolitinib versus standard therapy for the treatment of polycythemia vera. Volume 372.Pages 426-435. Copyright © 2015 Massachusetts Medical Society. Reproduced with permission from Massachusetts Medical Society.

Patients Achieving a ≥50% Reduction in MPN-SAF Total Symptom Score at Week 321a

At week 32, 49% of patients receiving

Jakafi and 5% of patients receiving BAT had

a ≥50% reduction in the 14-item

Myeloproliferative Neoplasm-Symptom

Assessment Form (MPN-SAF) total

symptom score.

The MPN-SAF diary was administered daily

in an electronic diary format to score 14

disease-related symptoms on a scale of 0

(absent) to 10 (worst possible).

RESPONSE was an open-label trial, so it

was not designed to evaluate differences in

symptoms.

? Disease-related symptoms are an

important consideration in PV. How are

symptom evaluations conducted in your

practice? Is this information used in clinical

decision making?



1

X

?

RESPONSE Exploratory Endpoint:Symptom Data• Patients receiving Jakafi had greater reductions in all symptom clusters reported, whereas patients

receiving BAT had an increase in scores of many symptoms

16

BAT, best available therapy; Wk, week.a Patients with data at both baseline (value >0) and week 32 were included in this analysis. Negative values indicate a reduction in the severity of symptoms.


-49.6%

-94.9%

-61.1%

-99.5% -100%

-51.5%-44%

-80.2%

-64.1%

-41.8%

0%

-37.1%

-93.9%

-65.9%

-4.2% -2.1%

0.4% 3.9%

-4.4%

11.1% 16.7%7.9% 5.0%

10.9%17.2% 15.7%

0% 1.4%

-100

-80

-60

-40

-20

0

20

40

Med

ian

Ch

an

ge in

Sym

pto

m S

co

re

Fro

m B

aselin

e t

o W

k 3

2 (

%)

Jakafi

BAT

Cytokine SymptomsHyperviscosity

Symptoms

Splenomegaly

Symptoms

From N Engl J Med. Vannucchi AM et al. Ruxolitinib versus standard therapy for the treatment of polycythemia vera. Volume 372. Pages 426-435. Copyright © 2015 Massachusetts Medical Society. Reproduced with permission from Massachusetts Medical Society.

Median Percentage Change in Symptom Score From Baseline to Week 32a

1

NEXT

r::,r.,, -~°-' ~0 ~ -~0 ~0 ~o~ r:,, ·r:l ~ "?-() 01/j ~~ iit0 flt() ~f/j 1$' -<..~0

~() ,l 0~ -~°-'"?-~ 'l>'fj 0~ -iJ-0 ~ "<'(lj ~->ca ~($ ~ ~o Q.._o

~(lj c,O g

-- ------- ------- ---- ------• ------

r::,r.,, r::,r.,, ~r.,, !..r.,, -~ 0 ~0 <vf/j ~~\0~ -~<:' -iJ-0 0'?S q_<..o -~

<S' ~ -~°-' -<..~ O' ~~ -o~ ~~~ & or.,,

0 .s.~ r::,r.,, "<''l><:' ~0 ~

I ~'5

.#, ~

~Cj

<v'l>~

L_

• •

~ if?::-

00 JP ~ c,O

()~

•

_J


5mg • 10mg • 15mg • 20mg • 25mg

RESPONSE Exploratory Endpoint:Symptom Data• Patients receiving Jakafi had greater reductions in all symptom clusters reported, whereas patients

receiving BAT had an increase in scores of many symptoms

BAT, best available therapy; Wk, week.a Patients with data at both baseline (value >0) and week 32 were included in this analysis. Negative values indicate a reduction in the severity of symptoms.


-49.6%

-94.9%

-61.1%

-99.5% -100%

-51.5%-44%

-80.2%

-64.1%

-41.8%

0%

-37.1%

-93.9%

-65.9%

-4.2% -2.1%

0.4% 3.9%

-4.4%

11.1% 16.7%7.9% 5.0%

10.9%17.2% 15.7%

0% 1.4%

-100

-80

-60

-40

-20

0

20

40

Med

ian

Ch

an

ge in

Sym

pto

m S

co

re

Fro

m B

aselin

e t

o W

k 3

2 (

%)

Jakafi

BAT

Cytokine SymptomsHyperviscosity

Symptoms

Splenomegaly

Symptoms

From N Engl J Med. Vannucchi AM et al. Ruxolitinib versus standard therapy for the treatment of polycythemia vera. Volume 372. Pages 426-435. Copyright © 2015 Massachusetts Medical Society. Reproduced with permission from Massachusetts Medical Society.

Median Percent Change in Symptom Score From Baseline to Week 32a

Patients receiving Jakafi had greater symptom

reduction than BAT across all 3 symptom

clusters.

Symptoms in PV can be due to cytokine

hyperactivity, hyperviscosity, or splenomegaly.

Patients in the RESPONSE trial reported

reductions in symptom scores across all 3 of

these symptom clusters.

RESPONSE was an open-label trial, so it was not

designed to evaluate differences in symptoms.

? How do you account for disease-associated

symptom drivers when assessing treatment

response in your practice?



1

X

---------------------------·

? .

RESPONSE Safety Profile

17

ALT, alanine aminotransferase; AST, aspartate aminotransferase; BAT, best available therapy.a National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0. b Includes dizziness and vertigo. c Includes dyspnea and dyspnea exertional. d Includes herpes zoster and post-herpetic neuralgia. e Includes weight increased and abnormal weight gain. f Includes urinary tract infection and cystitis. g Presented values are worst grade values regardless of baseline.


Clinically Relevant Laboratory Abnormalitiesg

Jakafi (n = 110) BAT (n = 111)

All Gradesa

(%)b

Grade 3

(%)

Grade 4

(%)

All Grades

(%)

Grade 3

(%)

Grade 4

(%)

Hem

ato

log

y Anemia 72 <1 <1 58 0 0

Thrombocytopenia 27 5 <1 24 3 <1

Neutropenia 3 0 <1 10 <1 0

Ch

em

istr

y

Hypercholesterolemia 35 0 0 8 0 0

Elevated ALT 25 <1 0 16 0 0

Elevated AST 23 0 0 23 <1 0

Hypertriglyceridemia 15 0 0 13 0 0

Adverse Reactions (incidence ≥5%)

Jakafi (n = 110) BAT (n = 111)

All Gradesa

(%)Grade 3/4

(%)All Grades

(%)Grade 3/4

(%)

Diarrhea 15 0 7 <1

Dizzinessb 15 0 13 0

Dyspneac 13 3 4 0

Muscle spasms 12 <1 5 0

Constipation 8 0 3 0

Herpes zosterd 6 <1 0 0

Nausea 6 0 4 0

Weight gaine 6 0 <1 0

Urinary tract infectionsf 6 0 3 0

Hypertension 5 <1 3 <1

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ALT, alanine aminotransferase; AST, aspartate aminotransferase; BAT, best available therapy.a National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0. b Includes dizziness and vertigo. c Includes dyspnea and dyspnea exertional. d Includes herpes zoster and post-herpetic neuralgia. e Includes weight increased and abnormal weight gain. f Includes urinary tract infection and cystitis. g Presented values are worst grade values regardless of baseline.


RESPONSE Safety Profile

Clinically Relevant Laboratory Abnormalitiesg

Jakafi (n = 110) BAT (n = 111)

All Gradesa

(%)b

Grade 3

(%)

Grade 4

(%)

All Grades

(%)

Grade 3

(%)

Grade 4

(%)

Hem

ato

log

y Anemia 72 <1 <1 58 0 0

Thrombocytopenia 27 5 <1 24 3 <1

Neutropenia 3 0 <1 10 <1 0

Ch

em

istr

y

Hypercholesterolemia 35 0 0 8 0 0

Elevated ALT 25 <1 0 16 0 0

Elevated AST 23 0 0 23 <1 0

Hypertriglyceridemia 15 0 0 13 0 0

Adverse Reactions (incidence ≥5%)

Jakafi (n = 110) BAT (n = 111)

All Gradesa

(%)Grade 3/4

(%)All Grades

(%)Grade 3/4

(%)

Diarrhea 15 0 7 <1

Dizzinessb 15 0 13 0

Dyspneac 13 3 4 0

Muscle spasms 12 <1 5 0

Constipation 8 0 3 0

Herpes zosterd 6 <1 0 0

Nausea 6 0 4 0

Weight gaine 6 0 <1 0

Urinary tract infectionsf 6 0 3 0

Hypertension 5 <1 3 <1

Discontinuation for AEs, regardless of

causality, was observed in 4% of

patients treated with Jakafi.

AE, adverse event.

Reference: Jakafi Prescribing Information. Wilmington,

DE: Incyte Corporation.

X

Important Safety Information

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Important Safety Information

19ANC, absolute neutrophil count.


• Treatment with Jakafi® (ruxolitinib) can cause thrombocytopenia, anemia and neutropenia,

which are each dose-related effects. Perform a pre-treatment complete blood count (CBC) and

monitor CBCs every 2 to 4 weeks until doses are stabilized, and then as clinically indicated

• Manage thrombocytopenia by reducing the dose or temporarily interrupting Jakafi. Platelet

transfusions may be necessary

• Patients developing anemia may require blood transfusions and/or dose modifications of Jakafi

• Severe neutropenia (ANC <0.5 × 109/L) was generally reversible by withholding Jakafi until

recovery

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Important Safety Information (continued)

20

• Serious bacterial, mycobacterial, fungal and viral infections have occurred. Delay starting Jakafi

until active serious infections have resolved. Observe patients receiving Jakafi for signs and

symptoms of infection and manage promptly. Use active surveillance and prophylactic

antibiotics according to clinical guidelines

• Tuberculosis (TB) infection has been reported. Observe patients taking Jakafi for signs and

symptoms of active TB and manage promptly. Prior to initiating Jakafi, evaluate patients for TB

risk factors and test those at higher risk for latent infection. Consult a physician with expertise in

the treatment of TB before starting Jakafi in patients with evidence of active or latent TB.

Continuation of Jakafi during treatment of active TB should be based on the overall risk-benefit

determination


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21

• Progressive multifocal leukoencephalopathy (PML) has occurred with Jakafi treatment. If PML is

suspected, stop Jakafi and evaluate

• Advise patients about early signs and symptoms of herpes zoster and to seek early treatment

• Increases in hepatitis B viral load with or without associated elevations in alanine

aminotransferase and aspartate aminotransferase have been reported in patients with chronic

hepatitis B virus (HBV) infections. Monitor and treat patients with chronic HBV infection

according to clinical guidelines


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22DIC, disseminated intravascular coagulation.


• When discontinuing Jakafi, myeloproliferative neoplasm-related symptoms may return within

one week. After discontinuation, some patients with myelofibrosis have experienced fever,

respiratory distress, hypotension, DIC, or multi-organ failure. If any of these occur after

discontinuation or while tapering Jakafi, evaluate and treat any intercurrent illness and consider

restarting or increasing the dose of Jakafi. Instruct patients not to interrupt or discontinue Jakafi

without consulting their physician. When discontinuing or interrupting Jakafi for reasons other

than thrombocytopenia or neutropenia, consider gradual tapering rather than abrupt

discontinuation

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23 Reference: Jakafi Prescribing Information. Wilmington, DE: Incyte Corporation.

• Non-melanoma skin cancers (NMSC) including basal cell, squamous cell, and Merkel cell

carcinoma have occurred. Perform periodic skin examinations

• Treatment with Jakafi has been associated with increases in total cholesterol, low-density

lipoprotein cholesterol, and triglycerides. Assess lipid parameters 8-12 weeks after initiating

Jakafi. Monitor and treat according to clinical guidelines for the management of hyperlipidemia

• Another JAK-inhibitor has increased the risk of major adverse cardiovascular events (MACE),

including cardiovascular death, myocardial infarction, and stroke (compared to those treated

with tumor TNF blockers) in patients with rheumatoid arthritis, a condition for which Jakafi is not

indicated. Consider the benefits and risks for the individual patient prior to initiating or continuing

therapy with Jakafi particularly in patients who are current or past smokers and patients with

other cardiovascular risk factors. Patients should be informed about the symptoms of serious

cardiovascular events and the steps to take if they occur

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• Another JAK-inhibitor has increased the risk of thrombosis, including deep venous thrombosis

(DVT), pulmonary embolism (PE), and arterial thrombosis (compared to those treated with TNF

blockers) in patients with rheumatoid arthritis, a condition for which Jakafi is not indicated. In

patients with myelofibrosis (MF) and polycythemia vera (PV) treated with Jakafi in clinical trials,

the rates of thromboembolic events were similar in Jakafi and control treated patients. Patients

with symptoms of thrombosis should be promptly evaluated and treated appropriately

• Another JAK-inhibitor has increased the risk of lymphoma and other malignancies excluding

NMSC (compared to those treated with TNF blockers) in patients with rheumatoid arthritis, a

condition for which Jakafi is not indicated. Patients who are current or past smokers are at

additional increased risk. Consider the benefits and risks for the individual patient prior to

initiating or continuing therapy with Jakafi, particularly in patients with a known secondary

malignancy (other than a successfully treated NMSC), patients who develop a malignancy, and

patients who are current or past smokers

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Please see the Full Prescribing Information

at www.jakafi.com/pdf/prescribing-information.pdf

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• In myelofibrosis and polycythemia vera, the most common nonhematologic adverse reactions

(incidence >15%) were bruising, dizziness, headache, and diarrhea. In acute graft-versus-host

disease, the most common nonhematologic adverse reactions (incidence >50%) were infections

(pathogen not specified) and edema. In chronic graft-versus-host disease, the most common

nonhematologic adverse reactions (incidence >20%) were infections (pathogen not specified)

and viral infections

• Avoid concomitant use with fluconazole doses greater than 200 mg. Dose modifications may be

required when administering Jakafi with fluconazole doses of 200 mg or less, or with strong

CYP3A4 inhibitors, or in patients with renal or hepatic impairment. Patients should be closely

monitored and the dose titrated based on safety and efficacy

• Use of Jakafi during pregnancy is not recommended and should only be used if the potential

benefit justifies the potential risk to the fetus. Women taking Jakafi should not breastfeed during

treatment and for 2 weeks after the final dose

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http://www.jakafi.com/pdf/prescribing-information.pdf

Monitor Your Patients With PV Regularly and Consider Jakafi for Appropriate Patients

Hct, hematocrit; HU, hydroxyurea; PV, polycythemia vera; WBC, white blood cell.a Jakafi is indicated for treatment of polycythemia vera (PV) in adults who have had an inadequate response to or are intolerant of hydroxyurea.

Jakafi and the Jakafi logo are registered trademarks of Incyte. All other trademarks are the property of their respective owners.

© 2021, Incyte Corporation. MAT-JAK-02671 10/21

Monitor your patients who are being treated with HU and phlebotomy

for clinical characteristics of advanced PV• Defined as elevated Hct ≥45% plus either elevated WBC >11 × 109/L or disease-related

symptoms despite treatment with maximum tolerated dose of HU and phlebotomy

Counsel patients about how actively monitoring blood counts and

symptoms helps you evaluate for changes in their disease

Educate appropriate patients about Jakafi as a potential

treatment optiona

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