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                                    control  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     PV[1]   *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:                                      [IMG]  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  therapy."  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  study[1].  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  atwww.jakavi.com.  Disclaimer 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  http://www.novartis.com.  Novartis   is    on    Twitter.   Sign    up    to   follow    @Novartis    at  http://twitter.com/novartis.  References [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: http://www.lls.org/content/nationalcontent/resourcecenter/freeeducationmaterials/mpd/pdf/ polycythemiavera.pdf. Accessed on April 28, 2014. [3] Barbui T, Finazzi G. Treatment of polycythemia vera. Haematologica.1998:83:143-149. [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]. 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