NOVARTIS FINANCE S.A. : Novartis drug Zortress® is first in over a decade approved by FDA to prevent organ rejection in adult

  NOVARTIS FINANCE S.A. : Novartis drug Zortress® is first in over a decade
approved by FDA to prevent organ rejection in adult liver transplant patients

NOVARTIS FINANCE S.A. / Novartis drug Zortress® is first in over a decade
approved by FDA to prevent organ rejection in adult liver transplant patients
. Processed and transmitted by Thomson Reuters ONE. The issuer is solely
responsible for the content of this announcement.

  *Zortress is the first mTOR inhibitor approved to prevent organ rejection
    in adult liver transplant patients in the US, where it is already approved
    for kidney transplantation
  *Approval based on positive outcomes from largest liver transplant study
    ever, comparing Zortress plus reduced-exposure tacrolimus to standard
  *Under trade name Certican^®, the drug was approved by European Health
    Authorities for use in adult liver transplant patients in the fourth
    quarter of 2012

Basel, February 15, 2013 - Novartis announced today that the US Food and  Drug 
Administration (FDA) has approved Zortress^® (everolimus) for the  prophylaxis 
of organ rejection in adult patients receiving a liver transplant. Zortress is
the first  mammalian target  of rapamycin  (mTOR) inhibitor  approved for  use 
following liver  transplantation.  It  is  also  the  first  immunosuppressant 
approved  by   the  FDA   in   over  a   decade   for  use   following   liver 

"Novartis has been a leading innovator  in the transplant field for 30  years, 
and this FDA approval for  liver transplantation marks an important  milestone 
for patients and their transplant physicians  in the US," said David  Epstein, 
Division  Head  of  Novartis  Pharmaceuticals.  "This  second  indication  for 
Zortress in just three years in  the US follows the recent European  approval, 
further underscoring Novartis'  continued commitment to  bringing much  needed 
treatment options to the transplant community worldwide."

The approval was based  on the largest liver  transplant study to date,  which 
showed that Zortress plus  reduced tacrolimus led  to comparable efficacy  and 
10mL/min higher renal function as measured by estimated glomerular  filtration 
rate (eGFR) for Zortress compared to standard tacrolimus at 12 months[1].

A large independent registry  study of nearly 70,000  patients who received  a 
non-renal solid  organ  transplant  between  1990 and  2000  showed  that  the 
incidence of chronic renal failure was greater in liver transplant  recipients 
than in recipients  of all  other solid organ  transplants, except  intestinal 
transplants[2]. Calcineurin inhibitors (CNIs), such as tacrolimus, are part of
the  standard-of-care  treatment  regimen   for  immunosuppression  in   liver 
transplantation, but  they  can  contribute to  adverse  reactions,  including 
impaired renal function[3],[4]. Zortress works by binding to a protein  called 
mTOR, and acts synergistically with CNIs, offering an opportunity to lower CNI

European  Health  Authorities   approved  Certican^®   (everolimus)  for   the 
prophylaxis of organ rejection in adult patients receiving a liver  transplant 
in the fourth quarter of 2012. In  most EU member countries, Certican is  also 
approved in kidney and heart transplantation.  In the US, Zortress is  already 
approved for use in adult kidney transplant patients[1].

Pivotal Study Details: Zortress Plus Reduced-Exposure Tacrolimus
The US approval was based on  12-month results from a Phase III,  multicenter, 
open-label, randomized,  controlled study  conducted in  719 liver  transplant 
patients starting 30 days post-transplant. In  the study, during the first  30 
days after transplant and prior to randomization, patients received tacrolimus
and corticosteroids,  with  or  without mycophenolate  mofetil.  No  induction 
antibody was administered[1].

Thirty days following liver transplantation,  patients were randomized to  one 
of three  groups: Zortress  (C[0] 3-8ng/mL)  plus reduced-exposure  tacrolimus 
(C[0] 3-5ng/mL)  (n=245), Zortress  (C[0]  6-10ng/mL) followed  by  tacrolimus 
withdrawal at  four  months  (n=231)  or  standard-exposure  tacrolimus  (C[0] 
6-10ng/mL) only (control,  n=243). All three  study arms included  twice-daily 
treatment. Additionally, all  arms included corticosteroids  for at least  six 
months post-transplant.Enrollment  into  the  tacrolimus  withdrawal  arm  was 
prematurely halted due to a higher  incidence of acute rejection episodes  and 
adverse reactions leading to  treatment discontinuation, clustered around  the 
time of tacrolimus elimination at four months post randomization. Therefore, a
treatment  regimen   of   Zortress   with  tacrolimus   elimination   is   not 

The efficacy  failure endpoint  at 12  months included  treated biopsy  proven 
acute rejection (tBPAR), graft loss, death  or loss to follow-up by month  12. 
Loss to follow-up represented patients who did not experience tBPAR, death  or 
graft loss, and whose last contact date was prior to the 12-month visit. Study
results showed that Zortress  plus reduced-exposure tacrolimus was  comparable 
to  standard-exposure  tacrolimus  with  respect  to  efficacy  failure.   The 
incidence of efficacy failure was lower in the Zortress plus  reduced-exposure 
tacrolimus group compared to the tacrolimus control group at month 12 (9%  vs. 
13.6%, respectively).  The difference  in rates  (Zortress vs.  control)  with 
97.5% CI for the  efficacy failure endpoint was  -4.6% (-11.4%, 2.2%) and  the 
difference in rates for  the graft loss, death  or loss to follow-up  endpoint 
was -0.1% (-5.4%, 5.3%)[1].

The main safety objective was evolution of renal function. The estimated  mean 
glomerular filtration rate for  the Zortress plus reduced-exposure  tacrolimus 
group was  80.9  mL/min/1.73m^2 and  the  tacrolimus control  group  was  70.3 
mL/min/1.73m^2 at  12  months  post-transplant in  the  intent-to-treat  (ITT) 

Please see US prescribing information at:

About Zortress (everolimus)
Everolimus is one of the most-extensively studied immunosuppressants in  solid 
organ transplantation with more than 10,000 transplant recipients enrolled  in 
Novartis-sponsored  clinical  trials  worldwide[7].   Under  the  trade   name 
Certican^®, it  is  approved  in  more than  90  countries  to  prevent  organ 
rejection for  renal  and  heart  transplant patients,  and  in  addition,  is 
approved in the EU  and other countries worldwide  to prevent organ  rejection 
for liver transplant patients. In the US, under the trade name Zortress^®, the
drug is approved for the prophylaxis  of organ rejection in adult patients  at 
low-moderate immunologic  risk  receiving a  kidney  transplant, and  is  also 
approved in adult patients following a liver transplant.

Everolimus is also available from  Novartis in different dosage strengths  and 
for different uses in non-transplant patient populations under the brand names
Afinitor^® and  Votubia^®.  It is  also  exclusively licensed  to  Abbott  and 
sublicensed to Boston Scientific for use in drug-eluting stents.

Not all  indications are  available in  every country.  As an  investigational 
compound, the  safety and  efficacy profile  of everolimus  has not  yet  been 
established outside the  approved indications. Because  of the uncertainty  of 
clinical  trials,  there   is  no  guarantee   that  everolimus  will   become 
commercially available for additional indications anywhere else in the world.

The  foregoing  release  contains  forward-looking  statements  that  can   be 
identified  by   terminology  such   as  "commitment,"   "will,"  or   similar 
expressions, or  by express  or implied  discussions regarding  potential  new 
indications or labeling for everolimus, or regarding potential future revenues
from everolimus. 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  everolimus  to  be  materially 
different from any  future results, performance  or achievements expressed  or 
implied by such statements. There can be no guarantee that everolimus 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 
everolimus will achieve  any particular levels  of revenue in  the future.  In 
particular, management's expectations regarding  everolimus could be  affected 
by,  among  other  things,   unexpected  clinical  trial  results,   including 
unexpected new clinical  data and unexpected  additional analysis of  existing 
clinical  data;  unexpected  regulatory   actions  or  delays  or   government 
regulation generally; the company's  ability to obtain  or maintain patent  or 
other proprietary intellectual  property protection;  competition in  general; 
government,  industry  and  general   public  pricing  pressures;   unexpected 
manufacturing issues; 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 
impairment  and  amortization  charges).   Novartis  Group  companies   employ 
approximately 128,000 full-time-equivalent associates and operate in more than
140  countries  around   the  world.  For   more  information,  please   visit

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

[1] Zortress^® (everolimus) US Prescribing Information, February 2013.
[2] Ojo, A., Held, P., Port, F., et al. Chronic Renal Failure after
Transplantation of a Nonrenal Organ. New Eng J Med, 2003;349:931-940.
[3] McGuire B.M., Rosenthal P., Brown C.C., et al. Long-term Management of the
Liver Transplant Patient: Recommendations for the Primary Care Doctor. Am J
Transplant, 2009;9:1988-2003.
[4] Venkataramanan, R., Shaw, L.M., Sarkozi, L., et al. Clinical Utility of
Monitoring Tacrolimus Blood Concentrations in Liver Transplant Patients. J
Clin Pharmacol, 2001;41:542-551.
[5] Schuurman, HJ., Cottens, S., Fuchs, S., et al. SDZ RAD, A New Rapamycin
Derivative: Synergism with Cyclosporine. Trans, 1997;64,1;32-35.
[6] De Simone, P., Nevens, F., De Carlis, L., et al. Everolimus with reduced
tacrolimus improves renal function in de novo liver transplant recipients: a
randomized controlled trial. Am J Transplant. 2012.
[7] Novartis Data on File. July 2012.

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