Novartis International AG : Novartis drug Jakavi® improved overall survival of myelofibrosis patients and impacted an

Novartis International AG : Novartis drug Jakavi® improved overall survival of
    myelofibrosis patients and impacted an underlying mechanism of disease

Novartis International AG / Novartis drug Jakavi® improved overall survival of
myelofibrosis patients and impacted an underlying mechanism of disease .
Processed and transmitted by Thomson Reuters ONE. The issuer is solely
responsible for the content of this announcement.

  *Jakavi^® reduced risk of death by 52% and sustained reductions in spleen
    size in new three-year COMFORT-II study data
  *Analysis from a separate trial suggested that long-term treatment with
    Jakavi may stabilize or improve bone marrow fibrosis, a key marker of
    worsening disease
  *Jakavi continues to be well tolerated in myelofibrosis patients after
    three years of treatment

Basel, June  16, 2013-  Novartis  today announced  results  from a  Phase  III 
three-year follow-up  study that  showed Jakavi^®  (ruxolitinib)  demonstrated 
improved overall survival and sustained reductions in spleen size compared  to 
conventional therapy.  In a  separate long-term  exploratory analysis,  Jakavi 
slowed or  stabilized the  advancement of  bone marrow  fibrosis, one  of  the 
underlying disease  mechanisms and  consequences of  myelofibrosis, an  effect 
that has not been observed with conventional therapy in advanced myelofibrosis

Findings are  being presented  at the  18^th Congress  of European  Hematology 
Association (EHA) in Stockholm, Sweden.

In a three-year follow-up analysis  of the COMFORT-II study, patients  treated 
with Jakavi demonstrated  an overall survival  advantage compared to  patients 
receiving conventional therapy. A 52% reduction in risk of death was  observed 
in the  Jakavi  arm  compared  with conventional  therapy  (HR=0.48;  95%  CI, 
0.28-0.85; p=0.009)[1], and the estimated probability of overall survival  was 
significantly greater  with  Jakavi  compared  to  conventional  therapy  (81% 
compared to 61%, respectively) at  144 weeks. Additionally, 51.4% of  patients 
treated with Jakavi achieved a >=35%  reduction from baseline in spleen  size. 
Patients continue to maintain  their spleen response,  with the median  spleen 
reduction not yet reached in the study.

The results  are  consistent  with previous  COMFORT-II  and  COMFORT-I  study 
analyses, which demonstrate that Jakavi provides significant clinical benefits
over  conventional   therapy  and   placebo   for  patients   suffering   from 
myelofibrosis, a rare blood cancer.

"Jakavi is the first drug to demonstrate an improvement in overall survival in
patients with  advanced  myelofibrosis,"  said Dr.  Alessandro  M.  Vannucchi, 
Department of Hematology, University of Florence, Italy and lead study author.
"Moreover, we are encouraged  by these latest  study results, which  reinforce 
that the rapid, positive effects of Jakavi in improving patients' symptoms are
sustained over the long-term."

Myelofibrosis develops when uncontrolled signaling in the JAK pathway -  which 
regulates blood cell production - causes the body to make blood cells that  do 
not work properly,  which scars  the bone marrow  and results  in an  enlarged 
spleen and  other severe  complications[2],[3].  Jakavi directly  targets  the 
underlying mechanism of the disease  and it significantly reduces spleen  size 
and improves symptoms regardless of JAK mutational status, disease subtype  or 
any prior treatment[4],[5],[6],[7],[8].

Data  were  also  presented  from  an  exploratory  analysis  of  bone  marrow 
morphology  from  a  separate  Phase  I/II  trial  of  Jakavi,  compared  with 
historical controls  from patients  treated with  conventional therapy.  After 
four years  of  Jakavi therapy,  bone  marrow  fibrosis improved  in  22%  and 
stabilized in 56% of patients with myelofibrosis. A comparable effect was  not 
seen with long-term conventional therapy.[9]

"For the first time in advanced myelofibrosis, drug therapy showed evidence of
bone marrow  fibrosis stabilization  or improvement,  further supporting  that 
Jakavi may modify the natural course of disease," said Alessandro Riva,  M.D., 
Global Head,  Oncology Development  and  Medical Affairs,  Novartis  Oncology. 
"These data are of great  interest because bone marrow transplantation,  which 
carries a  high risk  of morbidity  and mortality,  is the  only other  option 
proven  to   impact   bone  marrow   fibrosis   in  patients   with   advanced 

COMFORT-II Three-Year Long-Term Study Background
In the three-year analysis of COMFORT-II (COntrolled MyeloFibrosis Study  with 
ORal JAK Inhibitor  Therapy), a  total of 45.2%  of patients  remained on  the 
Jakavi treatment arm,  while all patients  randomized to conventional  therapy 
discontinued treatment. For  patients on conventional  therapy, 61.6%  crossed 
over to the Jakavi treatment arm, with 48.9% of these patients ongoing in  the 
extension  phase  of  the  study.  The  median  duration  of  Jakavi  exposure 
(randomized and  extension  phases) was  136  weeks and  conventional  therapy 
exposure (randomized  treatment  only)  was 45  weeks.  Overall  survival  was 
estimated using the Kaplan-Meier method.

All AEs were consistent with previous  analyses of treatment with Jakavi.  The 
most common hematologic AEs in either arm (Jakavi, conventional therapy)  were 
anemia (50.0%; 16.4%)  and thrombocytopenia  (50.7%; 13.7%).  The most  common 
non-hematologic abnormalities  for  each arm  (Jakavi,  conventional  therapy) 
include peripheral edema  (swelling of extremities)  (36.3%; 28.8%),  diarrhea 
(32.2%; 17.8%) and asthenia (weakness) (24.0%; 12.3%)[1].

A total of 191 patients were exposed  to Jakavi by the data cut-off date,  146 
patients initially  randomized  to  Jakavi  treatment  and  45  patients  that 
eventually  crossed  over  from   the  conventional  therapy  arm.   Treatment 
discontinuations in the Jakavi arm were primarily due to adverse events  (AEs) 
(16.4%)  and  disease  progression  (15.1%),  while  discontinuations  in  the 
conventional therapy arm were  primarily due to  consent withdrawal and  other 
reasons (12.3% each). Only  two patients discontinued due  to anemia (1%)  and 
seven patients due to thrombocytopenia (3.6%).

Long-Term Bone Marrow Morphology Analysis Background
The data  from  this separate  exploratory  analysis assessed  the  effect  of 
long-term  Jakavi  treatment  on  bone  marrow  morphology  in  patients  with 
myelofibrosis. An analysis of trephine biopsies were obtained from the  cohort 
of  myelofibrosis  patients   treated  at  MD   Anderson  Cancer  Center   who 
participated in Study 251, a Phase I/II trial of ruxolitinib[9].

Biopsies of  myelofibrosis  patients  treated with  Jakavi  were  obtained  at 
baseline, 24 months (68  patients) and 48 months  (18 patients). Samples  were 
also collected from a multicenter  observational database from three  European 
Union countries (160 biopsies in a cohort of 139 patients) in patients treated
with conventional  therapy  at 24  months  (97  patients) and  48  months  (63 

Bone marrow  fibrosis  grade (G)  changes  vs. baseline  were  categorized  as 
improvement, stabilization,  and  worsening  according  to  the  World  Health 
Organization (WHO) grading scale (0-3)  and reviewers were blinded to  patient 
characteristics and outcomes. Additional  analyses were performed on  biopsies 
from patients in the Jakavi-treated cohort: changes over time in the degree of
collagen deposition, amount of osteosclerosis (abnormal bone density) and bone
marrow cellularity[9]. Bone  marrow biopsies  of Jakavi  treated patients  who 
were evaluated at baseline presented with 21% G1 fibrosis, 53% G2 fibrosis and
26% G3 fibrosis. Distribution of baseline WHO fibrosis grades between  Jakavi- 
and conventionally- treated groups showed no noticeable difference (p=0.441 by
Cochran Mantel-Haenszel test)[9].

About Myelofibrosis
Myelofibrosis is a  life-threatening blood  cancer with a  poor prognosis  and 
limited  treatment   options[10],[11].  Studies   show  that   patients   with 
myelofibrosis have a decreased life expectancy, with a median overall survival
of 5.7  years[12].  Although allogeneic  stem  cell transplantation  may  cure 
myelofibrosis, the  procedure is  associated  with significant  morbidity  and 
transplant-related mortality,and is available to less than 5% of patients  who 
are young and fit enough to undergo the procedure[13].

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 45 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 US  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  is 15 mg  twice daily for  patients 
with a  platelet count  between 100,000cubic  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 

Jakavi is  a registered  trademark of  Novartis AG  in countries  outside  the 
United States. Jakafi is a registered trademark of Incyte Corporation.

Jakavi^® Important Safety Information
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 severe hepatic  or 
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,  bruising, 
bleeding and increased  blood pressure.  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[14].

Please see full Prescribing Information available at .

The  foregoing  release  contains  forward-looking  statements  that  can   be 
identified by terminology such as "suggested," "may," "encouraged," or similar
expressions, or by express or  implied discussions regarding potential  future 
revenues from Jakavi. You should not place undue reliance on these statements.
Such forward-looking  statements  reflect  the  current  views  of  management 
regarding future events,  and involve known  and unknown risks,  uncertainties 
and other factors that may cause  actual results with Jakavi to be  materially 
different from any  future results, performance  or achievements expressed  or 
implied by such statements. There can be no guarantee that Jakavi will achieve
any particular levels of  revenue in the  future. In particular,  management's 
expectations regarding  Jakavi  could  be affected  by,  among  other  things, 
unexpected regulatory actions  or delays or  government regulation  generally; 
unexpected clinical trial results, including unexpected new clinical data  and 
unexpected additional analysis of existing clinical data; government, industry
and  general  public  pricing  pressures;  unexpected  manufacturing   issues; 
competition in general; the company's ability to obtain or maintain patent  or 
other proprietary  intellectual  property  protection;  the  impact  that  the 
foregoing factors could have on the values attributed to the Novartis  Group's 
assets and liabilities as recorded in the Group's consolidated balance  sheet, 
and other risks and factors referred to in Novartis AG's current Form 20-F  on 
file with the  US Securities and  Exchange Commission. Should  one or more  of 
these risks  or uncertainties  materialize, or  should underlying  assumptions 
prove incorrect, actual  results may vary  materially from those  anticipated, 
believed, estimated or expected. 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 2012, the Group
achieved net sales of USD 56.7 billion, while R&D throughout the Group
amounted to approximately USD 9.3 billion (USD 9.1 billion excluding
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approximately 129,000 full-time-equivalent associates and operate in more than
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[1] 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.
[2] Leukemia & Lymphoma Society. Idiopathic myelofibrosis. Available at:
myelofibrosis/. Accessed April 2013.
[3] Mesa RA, Schwagera S, Radia D, et al. The Myelofibrosis Symptom Assessment
Form (MFSAF): an evidence-based brief inventory to measure quality of life and
symptomatic response to treatment in myelofibrosis. Leuk Res.
[4] Verstovsek S, Mesa RA, Gotlib J, et al. A Double-Blind, Placebo-Controlled
Trial of Ruxolitinib for Myelofibrosis. New Eng J Med. 2012: March
[5] Harrison C, Kiladjian JJ, Al-Ali HK, et al. JAK Inhibition with
Ruxolitinib versus Best Available Therapy for Myelofibrosis. New Eng J Med.
2012: March 1;366:787-98.
[6] Vannucchi A, Kiladjian JJ, Gisslinger H, et al. Reductions in JAK2V617F
Allele Burden with Ruxolitinib Treatment in COMFORT-II, a Phase III Study
Comparing the Safety and Efficacy of Ruxolitinib to Best Available Therapy
(BAT). 2012. Abstract #802. American Society of Hematology 2012. Annual
Meeting, Atlanta, GA.
[7] Harrison C, Kiladjian JJ, Gisslinger H, et al. Association of Cytokine
Levels and Reductions in Spleen Size in COMFORT-II, a Phase 3 Study Comparing
Ruxolitinib to Best Available Therapy (BAT). Abstract # 6625. American Society
of Clinical Oncology 2012 Annual Meeting, Chicago, IL.
[8] Cervantes, F, et al. Long-Term Safety, Efficacy, and Survival Findings
From COMFORT-II, a Phase 3 Study Comparing Ruxolitinib with Best Available
Therapy (BAT) for the Treatment of Myelofibrosis (MF) Blood. 2012. Abstract
#801. American Society of Hematology 2012 Annual Meeting. Atlanta, GA.)
[9] Kvasnicka, HM, et al. Long Term Intervention Effects on Bone Marrow
Morphology in Myelofibrosis: Patients Treated With Ruxolitinib and Best
Available Therapy. Abstract #S591.18^th Congress of European Hematology
Association (EHA). 2013. Stockholm, Sweden.
[10] Verstovsek S, Kantarjian H, Mesa RA, et al. Safety and Efficacy of JAK1 &
JAK2 Inhibitor, INCB018424, in Myelofibrosis. New Eng J Med. 2010 September
[11] Mesa RA, Schwagera S, Radia D, et al. The Myelofibrosis Symptom
Assessment Form (MFSAF): an evidence-based brief inventory to measure quality
of life and symptomatic response to treatment in myelofibrosis. Leuk Res.
[12] Cervantes F, Dupriez B, Pereira A, et al. New prognostic scoring system
for primary myelofibrosis based on a study of the International Working Group
for Myelofibrosis Research and Treatment. Blood. 2009;113:2895-2901.
[13] Patriarca F, Bacigalupo A, Sperotto A, et al. Allogeneic hematopoietic
stem cell transplantation in myelofibrosis: the 20-year experience of the
Gruppo Italiano Trapianto di Midollo Osseo (GITMO). Haematologica.
[14] JAKAVI [Summary of Product Characteristics]. Basel, Switzerland: Novartis
Pharma AG; 2012.

                                    # # #

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