(PR)Exjade* benefits chronically transfused patients with rare anemias by significantly reducing toxic iron that can damage key organs, according to landmark trial

        -  First prospective, multicentre study to show Exjade(*) removes
           iron from the heart in beta-thalassemia patients with mild to
           severe cardiac iron overload

        -  In a subgroup analysis of 341 patients with myelodysplastic
           syndromes (MDS), Exjade(*) significantly reduced levels of toxic
           iron

        -  These results are part of the largest prospective trial in iron
           chelation, which includes more than 1,700 patients with various
           transfusion-dependent anemias, including other rare anemias

    Dorval, QC, Dec. 9 /CNW/ - New data from the largest prospective trial in
iron chelation demonstrate the efficacy and safety of Exjade(*) (deferasirox) in
treating chronic transfusional iron overload, a potentially life-threatening
condition for patients who have had multiple blood transfusions to treat
underlying anemias, including beta-thalassemia, myelodysplastic syndromes
(MDS) and other rare anemias.
    Data from this landmark trial, known as EPIC, were presented today at the
50th American Society of Hematology (ASH) Annual Meeting and Exposition in San
Francisco, California.
    The EPIC cardiac substudy showed that Exjade(*) removed iron from the heart
in beta-thalassemia patients, based on a statistically significant improvement
in T2(*) magnetic resonance imaging, a validated technique to assess cardiac
iron content (P less than 0.0001). The one-year substudy included 114
beta-thalassemia patients with cardiac iron overload, the leading cause of
death in these patients.
    "These data clearly demonstrate that deferasirox significantly reduces
cardiac iron in beta-thalassemia patients with iron overload, which is a
critical goal of treatment for these patients," said Dudley Pennell, MD,
Professor of Cardiology, Royal Brompton and Harefield NHS Trust and Imperial
College, London. "Cardiac complications caused by the buildup of toxic iron in
the heart can be life-threatening for people living with thalassemia."
    A pre-planned analysis of 341 MDS patients enrolled in the study showed
that Exjade(*) significantly reduced levels of serum ferritin (SF), a key
measure of iron in the body, by 253.0 ng/mL from baseline (P=0.0019). Of the
171 MDS patients whose SF was measured at one year, the decrease from baseline
was 606 ng/mL.
    "Many MDS patients receive regular blood transfusions as part of their
ongoing treatment, which puts them at risk for iron overload," said Norbert
Gattermann, MD, PhD, Hematology, Oncology and Clinical Immunology, Heinrich
Heine University Medical Center, Dusseldorf, Germany. "This study, which
includes the largest number of MDS patients of any iron chelation study, shows
deferasirox can effectively reduce iron burden and is generally well tolerated
when used appropriately to treat these patients."
    Iron toxicity can lead to permanent damage of the liver, heart and
endocrine glands, leading to an increased risk of serious health problems and
early death. Previous studies of transfusion-dependent MDS patients have found
that increased levels of SF are associated with shortened overall survival.

    About the EPIC trial

    The EPIC trial was a one-year, open-label, prospective, multicentre
trial. EPIC studied the efficacy and safety of a fixed starting dose of
Exjade(*) based on transfusional iron intake, with subsequent dose titration at
3-monthly intervals based on serum ferritin (SF) trends. With 1,744 patients,
this trial is the largest ever conducted for an iron chelator and included the
largest cohorts of underlying anemias in a single trial, including patients
with beta-thalassemia, MDS, aplastic anemia and other rare anemias. Twelve
abstracts from EPIC are being presented at ASH.

    Study details

    The EPIC cardiac substudy evaluated the cardiac efficacy of Exjade(*) in
114 beta-thalassemia patients with myocardial siderosis (T2(*) less than 20 ms).
Baseline myocardial T2 was less than 10 milliseconds (ms) in 47 (41%) patients
(considered severe cardiac iron overload) and 10-20 ms in 67 (59%) patients
(considered mild to moderate). Mean baseline liver iron concentration (LIC)
was 28.2 +/-10.0 mg Fe/g dry weight (dw), median SF was 5235 ng/mL, and the
mean amount of transfused blood in the year prior to study entry was 185
mL/kg.
    Patients experienced a statistically significant increase in myocardial
T2(*) indicating a decrease in myocardial iron content. Based on a geometric
mean +/- coefficient of variation, change from baseline (11.2 ms +/-40.5%) to
12.9 ms +/-49.5% represents an increase by a factor of 1.16 from baseline (P
less than 0.0001). Overall, 69.5% of patients taking Exjade(*) had an
improvement in T2(*) (greater than 4% increase); there was no change in 14.3%;
and worsening (greater than 4% decrease) in 16.2% of patients. Left
ventricular ejection fraction remained stable throughout the study.
Additionally, LIC and SF levels (both indicators of total body iron) were
significantly reduced from baseline by -6.6 +/-9.9 mg Fe/g dw and -1257 ng/mL,
respectively (P less than 0.0001). Four patients discontinued treatment due to
adverse events. Most investigator-assessed drug-related adverse events were
mild to moderate in severity; rash was the most common (13.2%). There is an
ongoing one-year extension of this substudy.
    The pre-planned subgroup analysis of the EPIC study included 341 patients
with transfusion-dependent MDS and SF levels greater than or equal to 1000
ng/mL, or SF less than 1000 ng/mL, but with a history of multiple transfusions
(greater than 20 transfusions or 100 mL/kg of red blood cells) and an R2
MRI-confirmed LIC greater than 2 mg Fe/g dw. Overall, mean actual dose of
Exjade(*) over one year of treatment was 19.2 +/-5.4 mg/kg/day. Based on the
last observation carried forward statistical method, at one year, there was a
significant reduction in median SF from baseline (-253.0 ng/mL; P=0.0019,
n=341). Of the 171 MDS patients whose SF was measured at one year, the
decrease from baseline was 606 ng/mL. Overall, 48.7% of pts (n=166)
discontinued therapy. Most common investigator-assessed drug-related adverse
events were mild to moderate in severity and included diarrhea (n=110, 32%),
nausea (n=45, 13%), vomiting (n =26, 8%), abdominal pain (n=26, 8%), upper
abdominal pain (n=25, 7%), rash (n=23, 7%) and constipation (n=21, 6%).

    About Exjade(*)

    Exjade(*) has been granted a Notice of Compliance with Conditions by Health
Canada for the management of chronic iron overload in patients with
transfusion-dependent anemias aged six years or older. Exjade(*) is also
indicated in patients aged two to five who cannot be adequately treated with
deferoxamine.
    The results of key clinical trials have shown that Exjade(*), at doses of
20 to 30 mg/kg reduces liver iron concentration (LIC) and serum ferritin. With
its simple administration, Exjade(*) has the potential to significantly improve
patient compliance and quality of life.

    Exjade(*) important safety information

    The most frequent reactions reported during chronic treatment with
Exjade(*) in adult and pediatric patients include gastrointestinal disturbances
in about 26% of patients (mainly nausea, vomiting, diarrhea, or abdominal
pain), and skin rash in about 7% of patients. Mild, non-progressive,
dose-dependent increases in serum creatinine occurred in 34% of patients.
    Elevations of liver transaminases as suspected drug-related adverse
events were reported in about 2% of patients. The increases in liver
transaminases were not dose-dependent. Forty percent of these patients had
elevated levels (above the upper limit of normal) prior to receiving Exjade(*).
Elevations of transaminases greater than 10 times the upper limit of the
normal range, suggestive of hepatitis, were uncommon (0.3%). High frequency
hearing loss and lenticular opacities (early cataracts) have been observed in
less than 1% of patients treated with Exjade(*).
    Cases of acute renal failure (some with fatal outcome) have been reported
following the post-marketing use of Exjade(*).
    The use of Exjade(*) (deferasirox) is contraindicated in patients with
hypersensitivity to the active substance, deferasirox, or to any of the
excipients. Exjade(*) is contraindicated in patients with estimated creatinine
clearance less than 60 mL/min. It is recommended that Exjade(*) should not be
used during pregnancy.

    Disclaimer

    The foregoing release contains forward-looking statements that can be
identified by terminology such as "potentially," "can," "risk," "will," "may,"
or similar expressions, or by express or implied discussions regarding
potential new indications or labeling for Exjade(*) or regarding potential
future revenues from Exjade(*). 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 Exjade(*) to
be materially different from any future results, performance or achievements
expressed or implied by such statements. There can be no guarantee that
Exjade(*) will be approved for any additional indications or labeling in any
market. Nor can there be any guarantee that Exjade(*) will achieve any
particular levels of revenue in the future. In particular, management's
expectations regarding Exjade(*) 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; 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 Canada

    Novartis Pharmaceuticals Canada Inc., a leader in the healthcare field,
is committed to the discovery, development and marketing of innovative
products to improve the well-being of all Canadians. In 2007, the Company
invested over $86 million in research and development. Novartis
Pharmaceuticals Canada Inc. employs approximately 800 people in Canada and its
headquarters are located in Dorval, Quebec. It was named one of the "50 Best
Employers in Canada" in 2008. For further information, please consult
www.novartis.ca.

    About Novartis

    Novartis AG provides healthcare solutions that address the evolving needs
of patients and societies. Focused solely on healthcare, Novartis offers a
diversified portfolio to best meet these needs: innovative medicines,
cost-saving generic pharmaceuticals, preventive vaccines, diagnostic tools and
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in these areas. In 2007, the Group's continuing operations (excluding
divestments in 2007) achieved net sales of USD 38.1 billion and net income of
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companies employ approximately 97,000 full-time associates and operate in over
140 countries around the world. For more information, please visit
http://www.novartis.com.

    (*) Exjade is a registered trademark

For further information: Novartis Media Relations, Sabrina Tremblay,
Novartis Pharmaceuticals Canada Inc., Communications, (514) 633-7880 ext.
2254, (514) 880-9766 (mobile), sabrina.tremblay@novartis.com, e-mail:
media.relations@novartis.com