Novartis International AG: Pivotal Phase III data show polycythemia vera patients on Novartis drug Jakavi® achieved significant

   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
control . Processed and transmitted by NASDAQ OMX Corporate Solutions. The
issuer is solely responsible for the content of this announcement.

  *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[1]
  *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[2])  and 
reduced spleen size in patients with PV who are resistant to or intolerant  of 
hydroxyurea[1]. 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[2].  Currently, there  are  limited  treatments  for 
polycythemia vera and a high unmet need exists for new therapies that  provide 
effective disease control[3].

"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[2])  or spleen size  reductionin 
comparison with 20%  of patients  randomized to best  available therapy[1].  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[1].

"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[1].  Patients treated  with ruxolitinib  also experienced  a 
reduction  in  night  sweats  and   itchiness  (approximately  99%  and   95%, 
respectively)[4]. 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%,
respectively; p=.003)[1].

Ruxolitinib was well tolerated and  adverse events (AEs) were consistent  with 
those    previously    seen    in    ruxolitinib    studies    in    PV    and 
myelofibrosis[1],[5],[6]. 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)[1].  The 
most common non-hematologic  AEs were  headache, diarrhea  and fatigue,  which 
were mainly Grade 1 or 2[1]. 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[4].

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.

Study Design
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[1].

About Polycythemia Vera
PV is a chronic, incurable blood  cancer associated with an overproduction  of 
blood cells in the bone marrow[2] that affects roughly one to three people per
100,000 globally[7]. 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[2]. This  can 
cause  serious  cardiovascular  complications,   such  as  stroke  and   heart 
attack[2], resulting in  increased morbidity and  mortality[8]. 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[2].

Additionally, patients  with  PV  often  have  enlarged  spleen  and  numerous 
debilitating  symptoms  that  significantly  affect  their  daily  life[2].  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[9],[10].

About Jakavi
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[11].

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
approved indication.

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[11].   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 
or otherwise.

About Novartis
Novartis provides innovative  healthcare solutions that  address the  evolving 
needs of patients and societies. Headquartered in Basel, Switzerland, Novartis
offers a diversified portfolio to best meet these needs: innovative medicines,
eye  care,  cost-saving  generic  pharmaceuticals,  preventive  vaccines   and 
diagnostic tools, over-the-counter and animal health products. Novartis is the
only global company with leading positions in these areas. In 2013, the  Group 
achieved net  sales  of USD  57.9  billion,  while R&D  throughout  the  Group 
amounted  to  approximately  USD  9.9  billion  (USD  9.6  billion   excluding 
impairment  and  amortization  charges).   Novartis  Group  companies   employ 
approximately 135,000  full-time-equivalent associates  and sell  products  in 
more than 150 countries around the  world. For more information, please  visit

Novartis   is    on    Twitter.   Sign    up    to   follow    @Novartis    at

[1] 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.
[2] Leukemia & Lymphoma Society. "Polycythemia Vera Facts." Available at:
polycythemiavera.pdf. Accessed on April 28, 2014.
[3] Barbui T, Finazzi G. Treatment of polycythemia vera.
[4] Novartis Data on File.
[5] 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.
[6] 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.
[7] Titmarsh G, Duncombe A, McMullin M, et al. How common are
myeloproliferative neoplasms? A systematic review and meta-analysis.American
Journal of Hematology.2014:1-7.
[8] Finazzi G and Barbui T. How I treat patients with polycythemia vera.
Blood. 2007;109(12):5104-5111.
[9] 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.
[10] 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
Group. Br J Haematol. 1994;86(1):233-235.
[11] JAKAVI [Summary of Product Characteristics]. Basel, Switzerland: Novartis
Pharma AG; 2012.

                                    # # #

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