Market Overview

Four-Year Phase 3 Data Analysis Shows Durability of Response of Jakafi® (ruxolitinib) in Patients with Polycythemia Vera

Share:

- Long-term data reinforce Jakafi®
(ruxolitinib) as an effective long-term treatment option for patients
with polycythemia vera (PV) who have had an inadequate response to or
are intolerant of hydroxyurea

- Overall safety profile of Jakafi remained consistent with
previously-reported 80-week RESPONSE data

Incyte Corporation (NASDAQ:INCY) today announced new 208-week (4-year)
follow-up data from the ongoing, global, multi-center, open-label Phase
3 RESPONSE study of Jakafi® (ruxolitinib) comparing the
efficacy and safety of Jakafi with best available therapy (BAT) in
patients with polycythemia vera (PV) who are resistant to or intolerant
of hydroxyurea (HU). The pre-planned data analysis showed a durable
primary response to Jakafi in patients with PV who are resistant to or
intolerant of HU and the overall safety profile for Jakafi remained
consistent with previously reported 80-week RESPONSE data.1
The results were shared in an oral presentation today at the 59th
American Society of Hematology (ASH) Annual Meeting 2017 in Atlanta,
Georgia.

"With 30 months of additional follow-up, the four-year RESPONSE data
analysis presented today at ASH further reinforces the potential of
Jakafi as a long-term option for patients with PV," said Peg Squier,
M.D., Ph.D., Head of U.S. Medical Affairs at Incyte. "Given the few
treatment options available to treat this chronic and progressive blood
cancer, these long-term safety and efficacy data are meaningful to
patients with uncontrolled PV."

The 80-week follow-up results from RESPONSE confirmed that among
patients who initially responded to Jakafi treatment, the probability of
maintaining primary and hematocrit (Hct) responses for ≥ 80 weeks was
92% and 89%, respectively, and hence Jakafi could be an effective
long-term treatment option for patients with PV who are HU-resistant or
intolerant.

At the week 208 analysis, the overall long-term safety profile remained
consistent with the 80-week data analysis and the response was durable.
In both the Jakafi arm and the crossover population, around 30% of
patients completed the study treatment and 37% of patients were still
receiving treatment.

"These are clinically relevant long-term safety and efficacy results,
and further support the use of Jakafi in PV patients who have an
inadequate response to or are intolerant of hydroxyurea," said Srdan
Verstovsek, M.D., Ph.D., medical oncologist and professor, Department of
Leukemia at The University of Texas MD Anderson Cancer Center, Houston,
Texas.

About the RESPONSE Trial

RESPONSE is an ongoing, global, multi-center, open-label, Phase 3 trial
comparing the efficacy and safety of Jakafi® (ruxolitinib)
with BAT in 222 patients (Jakafi, 110; BAT, 112) with PV who are
resistant to or intolerant of hydroxyurea (HU).2

The primary response was a composite endpoint of the proportion of
patients who achieved both hematocrit (Hct) control (defined as no
phlebotomy eligibility from week 8 through week 32, with no more than 1
post-randomization phlebotomy eligibility up to week 8) and a spleen
volume reduction of at least 35% from baseline at week 32. Phlebotomy
eligibility was defined as an Hct >45% and at least 3 percentage points
greater than baseline or an Hct >48%. Patients randomized to BAT could
crossover (CO) to ruxolitinib at week 32 if they did not meet the
primary endpoint, or after week 32 in case of disease progression (PBT
eligibility, splenomegaly progression, or both).2

The primary endpoint of the RESPONSE study was achieved, demonstrating
that Jakafi was superior to BAT at controlling Hct and reducing spleen
volume at week 32.2 The 80-week follow-up results from
RESPONSE have been published previously and confirmed that ruxolitinib
could be an effective long-term therapy option for
HU-resistant/intolerant (R/I) patients with PV.3

Durability of the primary response, overall clinicohematologic (CLHM)
response (defined as Hct control, platelet count ≤ 400 × 109/L,
white blood cell count ≤ 10 × 109/L, and spleen volume
reduction ≥ 35% by imaging), as well as long-term safety were updated at
week 208.1

At week 208, the Kaplan-Meier (KM) estimate of duration of primary
response was 0.73 (95% CI: 0.49, 0.87), and the KM estimate of duration
of absence of PBT eligibility was 0.73 (95% CI: 0.60, 0.83). The KM
estimate of duration of at least 35% reduction in spleen volume was 0.86
(95% CI: 0.61, 0.95). Median duration of primary and CLHM responses has
not been reached.1

Out of the 70 patients (63.6%) in the Jakafi arm who achieved an overall
CLHM response at week 32, 21 had progressed by week 208. The KM estimate
of duration of complete hematological remission (defined as Hct control,
platelet count ≤ 400 × 109/L, and white blood cell count ≤ 10
× 109/L) at 208-weeks was 0.54 (95% CI: 0.31, 0.72). RESPONSE
data also demonstrated that the KM estimate for overall survival at
5-years was 90.6% (95% CI: 80.1, 95.7) for patients treated with Jakafi
compared to 87.7% (95% CI: 74.8, 94.3) for patients treated with BAT.1

At the week 208 analysis, 41 patients (37%) originally randomized to the
Jakafi arm were still receiving therapy (median exposure, 225 weeks)
versus no patients on BAT (median exposure, 34 weeks). Among patients in
the Jakafi arm, 29% completed the treatment as per protocol. Of the 98
patients who crossed over to Jakafi after week 32, 38% remained on
Jakafi (median exposure, 189 weeks) and 31% completed treatment. Other
main reasons for the study drug discontinuations (Jakafi + CO patients)
were disease progression (11% + 8%), patient decision (6% + 6%), and
adverse events (14% + 14%).1

The most common adverse events in the Jakafi randomized arm (week 208 vs
week 80) per 100 patient-years of exposure were anemia (9.3 vs 13.2),
pruritus (7.3 vs 9.7), diarrhea (7.1 vs 9.7), headache (6.1 vs 10.5),
arthralgia (5.9 vs 6.1), increased weight (5.6 vs 7.5) and muscle spasms
(5.4 vs 7.9).

The 208-week results (Abstract #322) were presented as a part of an oral
session (#634) on Sunday, December 10, 2017, 7:30-9:00 AM Eastern Time
(8:15 AM), Building C, Level 2, C208-C210.

About Polycythemia Vera (PV)

Polycythemia vera (PV) is a myeloproliferative neoplasm (MPN) and is
typically characterized by elevated hematocrit, the percent volume of
red blood cells in the blood, which can lead to a thickening of the
blood and an increased risk of blood clots. An elevated white blood cell
and/or platelet count may also be present.4 Patients with PV
who fail to consistently maintain appropriate hematocrit levels have a
four times higher risk of major thrombosis (blood clots) or
cardiovascular death.5 Patients with PV can also suffer from
an enlarged spleen and a significant symptom burden which may be
attributed to thickening of the blood and lack of oxygen to parts of the
body.6 Signs and symptoms of PV commonly include fatigue,
itching, night sweats, bone pain, fever, and unexplained weight loss.7

Approximately 100,000 patients in the U.S. are living with PV.8
Current standard treatment for PV is phlebotomy (the removal of blood
from the body) plus aspirin. When phlebotomy can no longer control PV,
chemotherapy such as hydroxyurea, or interferon, is utilized in
high-risk patients.9,10 Approximately one in four patients
with PV are considered uncontrolled11,12 because they have an
inadequate response to or are intolerant of hydroxyurea, the most
commonly used chemotherapeutic agent for the treatment of PV.

About Jakafi® (ruxolitinib)

Jakafi is a first-in-class JAK1/JAK2 inhibitor approved by the U.S. Food
and Drug Administration for treatment of people with polycythemia vera
(PV) who have had an inadequate response to or are intolerant of
hydroxyurea.

Jakafi is also indicated for treatment of people with intermediate or
high-risk myelofibrosis (MF), including primary MF, post–polycythemia
vera MF, and post–essential thrombocythemia MF.

Jakafi is marketed by Incyte in the United States and by Novartis as
Jakavi® (ruxolitinib) outside the United States. Jakafi is a
registered trademark of Incyte Corporation. Jakavi is a registered
trademark of Novartis AG in countries outside the United States.

Important Safety Information

Jakafi can cause serious side effects, including:

Low blood counts: Jakafi® (ruxolitinib) may cause
your platelet, red blood cell, or white blood cell counts to be lowered.
If you develop bleeding, stop taking Jakafi and call your healthcare
provider. Your healthcare provider will perform blood tests to check
your blood counts before you start Jakafi and regularly during your
treatment. Your healthcare provider may change your dose of Jakafi or
stop your treatment based on the results of your blood tests. Tell your
healthcare provider right away if you develop or have worsening symptoms
such as unusual bleeding, bruising, tiredness, shortness of breath, or a
fever.

Infection: You may be at risk for developing a serious infection
during treatment with Jakafi. Tell your healthcare provider if you
develop any of the following symptoms of infection: chills, nausea,
vomiting, aches, weakness, fever, painful skin rash or blisters.

Skin cancers: Some people who take Jakafi have developed certain
types of non-melanoma skin cancers. Tell your healthcare provider if you
develop any new or changing skin lesions.

Increases in Cholesterol: You may have changes in your blood
cholesterol levels. Your healthcare provider will do blood tests to
check your cholesterol levels during your treatment with Jakafi.

The most common side effects of Jakafi include: low platelet
count, low red blood cell counts, bruising, dizziness, headache.

These are not all the possible side effects of Jakafi. Ask your
pharmacist or healthcare provider for more information. Tell your
healthcare provider about any side effect that bothers you or that does
not go away.

Before taking Jakafi, tell your healthcare provider about: all
the medications, vitamins, and herbal supplements you are taking and all
your medical conditions, including if you have an infection, have or had
tuberculosis (TB), or have been in close contact with someone who has
TB, have or had hepatitis B, have or had liver or kidney problems, are
on dialysis, had skin cancer or have any other medical condition. Take
Jakafi exactly as your healthcare provider tells you. Do not change or
stop taking Jakafi without first talking to your healthcare provider. Do
not drink grapefruit juice while on Jakafi.

Women should not take Jakafi while pregnant or planning to become
pregnant, or if breast-feeding.

Full Prescribing Information, which includes a more complete
discussion of the risks associated with Jakafi, is available at 
www.jakafi.com.

About Incyte

Incyte Corporation is a Wilmington, Delaware-based biopharmaceutical
company focused on the discovery, development and commercialization of
proprietary therapeutics. For additional information on Incyte, please
visit the Company's website at www.incyte.com.

Follow @Incyte on Twitter at https://twitter.com/Incyte.

Forward-Looking Statements

Except for the historical information set forth herein, the matters set
forth in this press release, including statements regarding the
potential for Jakafi to be a long-term treatment for patients with PV,
contain predictions, estimates and other forward-looking statements.
These forward-looking statements are based on the Company's current
expectations and are subject to risks and uncertainties that may cause
actual results to differ materially, including unanticipated
developments and the risks related to the efficacy or safety of the
Company's development pipeline, the results of further research and
development, the high degree of risk and uncertainty associated with
drug development, clinical trials and regulatory approval processes,
other market or economic factors and competitive and technological
advances; and other risks detailed from time to time in the Company's
reports filed with the Securities and Exchange Commission, including its
Form 10-Q for the quarter ended September 30, 2017. Incyte disclaims any
intent or obligation to update these forward-looking statements.

References

  1. Kiladjian J, Verstovsek S, Griesshammer M, et al. Results From The
    208-Week (4-year) Follow-Up Of RESPONSE Trial, A Phase 3 Study
    Comparing Ruxolitinib (Rux) With Best Available Therapy (BAT) For The
    Treatment Of Polycythemia Vera (PV). Abstract #322. 59th American
    Society of Hematology (ASH) Annual Meeting 2017, Atlanta, Georgia, USA.
  2. Vannucchi AM, Kiladjian JJ, Griesshammer M, et al. Ruxolitinib versus
    standard therapy for the treatment of polycythemia vera. N Engl J Med.
    2015;372(5):426-435.
  3. Verstovsek S, Vannucchi AM, Griesshammer M, et al. Ruxolitinib versus
    best available therapy in patients with polycythemia vera: 80-week
    follow-up from the RESPONSE trial. Haematologica. 2016;101(7):821-829.
  4. Leukemia & Lymphoma Society. "Polycythemia Vera Facts." Available at: https://www.lls.org/sites/default/files/file_assets/FS13_PolycythemiaVera_FactSheet_final5.1.15.pdf.
    Accessed November 2015
    .
  5. Marchioli R, Finazzi G, Specchia G, et al. Cardiovascular Events and
    Intensity of Treatment in Polycythemia Vera. N Engl J Med.
    2013;368:22-33.
  6. National Institutes of Health. "What Are the Signs and Symptoms of
    Polycythemia Vera?" Available at: http://www.nhlbi.nih.gov/health/health-topics/topics/poly/signs.
    Accessed November 2015.
  7. Tefferi A. Polycythemia Vera and Essential Thrombocythemia: 2013
    Update on Diagnosis, Risk-Stratification, and Management. Am J
    Hematol. 2013;88:507-16.
  8. Data on file. Incyte Corporation.
  9. Vannucchi AM. How I treat polycythemia vera. Blood. 2014;
    124(22):3212-20.
  10. Passamonti F. How I treat polycythemia vera. Blood. 2012;
    120(2):275-84.
  11. Barosi G, Birgegard G, Finazzi G, et al. A Unified Definition of
    Clinical resistance and Intolerance to Hydroxycarbamide in
    Polycythaemia Vera and Primary Myelofibrosis: Results of a European
    LeukemiaNet (ELN) consensus process. Br J Haematol. 2010;149:961-3.
  12. Alvarez-Larrán A, Pereira A, Cervantes F, et al. Assessment and
    Prognostic Value of the European LeukemiaNet criteria for
    Clinicohematologic Response, Resistance, and Intolerance to
    Hydroxyurea in Polycythemia Vera. Blood. 2012;119:1363-9.

View Comments and Join the Discussion!