Novartis International AG: Pivotal Phase III data show polycythemia vera
patients on Novartis drug Jakavi® achieved significant improvement in disease
Novartis International AG / Pivotal Phase III data show polycythemia vera
patients on Novartis drug Jakavi® achieved significant improvement in disease
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*77% of patients on Jakavi^® (ruxolitinib) vs 20% on best available therapy
achieved hematocrit control or spleen reduction, key treatment goals in
*Nearly half of ruxolitinib-treated patients had a 50% or more reduction in
debilitating PV symptoms compared to 5% on best available therapy
*Global regulatory filings are underway based on these data; if approved,
ruxolitinib will be the first JAK 1/2 inhibitor available for PV patients
The digital press release with multimedia content can be accessed here:
Basel, June 3, 2014- Novartis today announced results from the first-ever
pivotal Phase III study evaluating a JAK 1/2 inhibitor for the treatment of
polycythemia vera (PV). Jakavi^® (ruxolitinib) significantly improved
hematocrit control without the need for phlebotomy (a procedure to remove
blood from the body to reduce the concentration of red blood cells) and
reduced spleen size in patients with PV who are resistant to or intolerant of
hydroxyurea. Findings are being presented at the 50th Annual Meeting of the
American Society of Clinical Oncology in Chicago, Illinois.
PV is a chronic, incurable blood cancer associated with an overproduction of
blood cells that can cause serious cardiovascular complications, such as
stroke and heart attack. Currently, there are limited treatments for
polycythemia vera and a high unmet need exists for new therapies that provide
effective disease control.
"Patients with polycythemia vera may not have their disease controlled with
existing therapies, increasing their risk for cardiovascular complications,"
said Srdan Verstovsek, MD, PhD, of MD Anderson Cancer Center, Houston, Texas
and lead study author. "In the RESPONSE trial, patients treated with
ruxolitinib showed better disease control, including controlled hematocrit
levels without the need for phlebotomy, reduced spleen size and improved
symptom management compared to current therapies."
At week 32 of the study, 77% of patients randomized to ruxolitinib achieved
one or both components of the composite endpoint of hematocrit control (volume
percentage of red blood cells in whole blood) or spleen size reductionin
comparison with 20% of patients randomized to best available therapy. A
significantly greater proportion of patients achieved the composite primary
endpoint when treated with ruxolitinib compared to best available therapy (21%
compared to 1%, respectively; p< .0001), and 91% of these patients treated
with ruxolitinib maintained their response at week 48.
"New treatments for polycythemia vera are greatly needed, as this is a disease
that causes debilitating daily symptoms, which are as severe as symptoms
associated with myelofibrosis, and also puts patients at risk for serious
cardiovascular complications, such as stroke and heart attack," said
Alessandro Riva, MD, Global Head, Novartis Oncology Development and Medical
Affairs. "These findings reinforce ruxolitinib's significant clinical benefit
and potential to become an important new treatment option for polycythemia
vera patients who are no longer responding to or are intolerant of prior
In the study, a 50% or more improvement in PV-related symptoms was seen in 49%
of ruxolitinib-treated patients compared to 5% of patients treated with best
available therapy. Patients treated with ruxolitinib also experienced a
reduction in night sweats and itchiness (approximately 99% and 95%,
respectively). In addition, a greater proportion of patients on the
ruxolitinib treatment arm achieved complete hematologic response as defined by
the modified 2009 European LeukemiaNet (ELN) criteria, a key secondary
endpoint, when compared to the best available therapy arm (24% compared to 9%,
Ruxolitinib was well tolerated and adverse events (AEs) were consistent with
those previously seen in ruxolitinib studies in PV and
myelofibrosis,,. Within the first 32 weeks of treatment, Grade 3 or 4
hematologic AEs in the ruxolitinib treatment arm were anemia (1.8%) and
thrombocytopenia (5.5%), and fewer patients treated with ruxolitinib
experienced thromboembolic events when compared to those who received best
available therapy (1 patient compared to 6 patients, respectively). The
most common non-hematologic AEs were headache, diarrhea and fatigue, which
were mainly Grade 1 or 2. Additionally, 3.6% of patients randomized to the
ruxolitinib treatment arm discontinued treatment due to AEs compared to 1.8%
on the best available therapy arm.
Data from the RESPONSE trial will support worldwide regulatory submissions
planned this year. The data will also be presented at the upcoming 19th
Congress of the European Hematology Association in Milan, Italy.
Ruxolitinib is currently approved in more than 60 countries for patients with
myelofibrosis, a debilitating and life-threatening blood cancer.
RESPONSE is a global, randomized, open-label study conducted at 109 sites. 222
patients with PV resistant to or intolerant of hydroxyurea were randomized 1:1
to receive either ruxolitinib (starting dose of 10 mg twice-daily) or best
available therapy, which was defined as investigator selected monotherapy or
observation only. Ruxolitinib dose was adjusted as needed throughout the
The primary endpoint of the study was the proportion of patients whose
hematocrit was controlled without phlebotomy from week 8 through 32 and whose
spleen volume was reduced by 35% or more from baseline as assessed by imaging
at 32 weeks. In addition, efficacy was further assessed using two key
secondary endpoints: durable primary response and complete hematological
remission. Other endpoints include safety, symptom improvement (as measured by
the MPN-SAF 14-item total symptom score) and quality of life.
About Polycythemia Vera
PV is a chronic, incurable blood cancer associated with an overproduction of
blood cells in the bone marrow that affects roughly one to three people per
100,000 globally. It is typically characterized by an elevated hematocrit,
the volume percentage of red blood cells in whole blood, which can lead to a
thickening of the blood and an increased risk of blood clots. This can
cause serious cardiovascular complications, such as stroke and heart
attack, resulting in increased morbidity and mortality. Phlebotomy, a
procedure to remove blood from the body to reduce the concentration of red
blood cells, is commonly used to maintain a normal hematocrit level.
Additionally, patients with PV often have enlarged spleen and numerous
debilitating symptoms that significantly affect their daily life. A
proportion of patients become intolerant or resistant to currently available
therapies. In fact, approximately 25% of PV patients become resistant to or
intolerant of hydroxyurea treatment, which results in inadequate disease
control and an increased risk of progression,.
Jakavi (ruxolitinib) is an oral inhibitor of the JAK 1 and JAK 2 tyrosine
kinases and was approved by the European Commission in August 2012 for the
treatment of disease-related splenomegaly or symptoms in adult patients with
primary myelofibrosis (also known as chronic idiopathic myelofibrosis),
post-polycythemia vera myelofibrosis or post-essential thrombocythemia
myelofibrosis. Jakavi is approved in more than 60 countries, including the
European Union, Canada and some countries in Asia, Latin and South America.
Additional worldwide regulatory filings are underway.
Novartis licensed ruxolitinib from Incyte Corporation for development and
commercialization outside the United States. Both the European Commission and
the U.S. Food and Drug Administration (FDA) granted ruxolitinib orphan drug
status for myelofibrosis. Jakavi is marketed in the United States by Incyte
Corporation under the name Jakafi^®for the treatment of patients with
intermediate or high-risk myelofibrosis.
The recommended starting dose for Jakavi in patients with myelofibrosis is 15
mg twice daily for patients with a platelet count between 100,000 cubic
millimeters (mm^3) and 200,000 mm^3, and 20 mg twice daily for patients with a
platelet count of >200,000 mm^3. Doses may be titrated based on safety and
efficacy. There is limited information to recommend a starting dose for
patients with platelet counts between 50,000/mm^3 and <100,000/mm^3. The
maximum recommended starting dose in these patients is 5 mg twice daily, and
patients should be titrated cautiously.
Jakavi is a registered trademark of Novartis AG in countries outside the
United States. Jakafi is a registered trademark of Incyte Corporation. The
safety and efficacy profile of Jakavi has not yet been established outside the
Jakavi Important Safety Information for Treatment of Myelofibrosis
Jakavi can cause serious side effects, including a decrease in blood cell
count and infections. Complete blood count monitoring is recommended. Dose
reduction or interruption may be required in patients with any hepatic
impairment or severe renal impairment or in patients developing hematologic
adverse reactions such as thrombocytopenia, anemia and neutropenia. Dose
reductions are also recommended when Jakavi is co-administered with strong
CYP3A4 inhibitors or fluconazole. Use of Jakavi during pregnancy is not
recommended, and women should avoid becoming pregnant during Jakavi therapy.
Women taking Jakavi should not breast feed. The most common adverse drug
reactions, occurring at any level of severity (incidence >10%) are urinary
tract infections, anemia, thrombocytopenia, neutropenia, hypercholesterolemia,
dizziness, headache, alanine aminotransaminase increased, asparte
aminotransferase increased and bruising. Other common adverse drug reactions
(incidence 1 to 10%) are herpes zoster, weight gain, flatulence and
tuberculosis (1%). Progressive multifocal leukencephalopathy (PML) has been
reported. Physicians should be alert for neuropsychiatric symptoms suggestive
of PML. Please see full Prescribing Information available
The foregoing release contains forward-looking statements that can be
identified by words such as "underway," "will," "being presented," "can,"
"may," "potential," "to become," "planned," "upcoming," "should," "has not
yet," or similar terms, or by express or implied discussions regarding
potential new indications or labeling for Jakavi, or regarding potential
future revenues from Jakavi. You should not place undue reliance on these
statements. Such forward-looking statements are based on the current beliefs
and expectations of management regarding future events, and are subject to
significant known and unknown risks and uncertainties. Should one or more of
these risks or uncertainties materialize, or should underlying assumptions
prove incorrect, actual results may vary materially from those set forth in
the forward-looking statements. There can be no guarantee that Jakavi will be
submitted or approved for any additional indications or labeling in any
market, or at any particular time. Nor can there be any guarantee that Jakavi
will be commercially successful in the future. In particular, management's
expectations regarding Jakavi could be affected by, among other things, the
uncertainties inherent in research and development, including unexpected
clinical trial results and additional analysis of existing clinical data;
unexpected regulatory actions or delays or government regulation generally;
the company's ability to obtain or maintain proprietary intellectual property
protection; general economic and industry conditions; global trends toward
health care cost containment, including ongoing pricing pressures; unexpected
manufacturing issues, and other risks and factors referred to in Novartis AG's
current Form20-F on file with the US Securities and Exchange Commission.
Novartis is providing the information in this press release as of this date
and does not undertake any obligation to update any forward-looking statements
contained in this press release as a result of new information, future events
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 Verstovsek S, et al. Results of a prospective, randomized, open-label
Phase III study of ruxolitinib in polycythemia vera patients resistant to or
intolerant of hydroxyurea: The RESPONSE Trial. Abstract #7026. 50th American
Society of Clinical Oncology (ASCO) Chicago, IL.
 Leukemia & Lymphoma Society. "Polycythemia Vera Facts." Available at:
polycythemiavera.pdf. Accessed on April 28, 2014.
 Barbui T, Finazzi G. Treatment of polycythemia vera.
 Novartis Data on File.
 Vannucchi, A, et al. Long-Term Outcomes From A Phase 3 Study Comparing
Ruxolitinib With Best Available Therapy (BAT) For The Treatment of
Myelofibrosis (MF): A 3 Year Update of Comfort II. Abstract #S1111.18^th
Congress of European Hematology Association (EHA), 2013. Stockholm, Sweden.
 Verstovsek S, Ruben M, Gotlib J, et al. Long-Term Outcome of Ruxolitinib
Therapy in Patients with Myelofibrosis: 3-Year Update From COMFORT-I. Abstract
#396. 55th American Society of Hematology (ASH) Annual Meeting and Exposition,
2013. New Orleans, LA.
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Journal of Hematology.2014:1-7.
 Finazzi G and Barbui T. How I treat patients with polycythemia vera.
 Alvarez-Larran A, 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(6):1363-1369.
 Najean Y, Dresch C, Rain JD. The very-long-term course of polycythaemia:
a complement to the previously published data of the Polycythaemia Vera Study
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 JAKAVI [Summary of Product Characteristics]. Basel, Switzerland: Novartis
Pharma AG; 2012.
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