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Novartis drug Exjade® first treatment approved by FDA for chronic iron overload in patients with non-transfusion-dependent thalassemia



2013-01-23 21:31:56 -


Novartis International AG /
Novartis drug Exjade® first treatment approved by FDA for chronic iron overload
in patients with non-transfusion-dependent thalassemia
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The issuer is solely responsible for the content of this announcement.

* Pivotal placebo-controlled study data show Exjade significantly decreases
iron burden in NTDT patients versus placebo, with similar overall adverse
event rate[1]

* Patients with NTDT accumulate excess iron increasing their risk of
complications, including liver fibrosis, cirrhosis, blood clots, and bone
and vascular disease[2]

* At least three quarters of a million people worldwide have NTDT[3]-[5] and
many patients are undiagnosed until serious symptoms arise[6]

Basel, January 23, 2013 - Novartis announced today that the US Food and Drug
Administration (FDA) has approved Exjade(®) (deferasirox) for the treatment of
chronic iron overload in patients 10 years of age and older with non-
transfusion-dependent thalassemia (NTDT) syndromes and with a liver iron
concentration of at least 5 mg of iron per gram dry weight and a serum ferritin
measurement greater than 300 micrograms per liter. Exjade is the first treatment
indicated for patients with these types of thalassemia in the United States.

The approval is based on results from the first prospective placebo-controlled
study of iron chelation in NTDT patients, THALASSA, which showed a significant
dose-dependent decrease in iron burden compared to placebo (p<0.001)[1]. In this
pivotal study, Exjade significantly reduced the concentration of iron in the
liver, known as liver iron concentration (LIC), as well as the amount of iron
anywhere in the body, measured by serum ferritin[1]. The overall adverse event
rate for Exjade was similar to the placebo arm[1].

"Patients with NTDT can suffer severe and life-changing complications from
chronic iron overload," said Elliott Vichinsky, MD, Medical Director,
Hematology/Oncology, Children's Hospital and Research Center, Oakland,
California. "In these thalassemia patients, excess iron starts to accumulate at
birth yet is often undetected until serious symptoms appear in early adulthood.
With this approval of Exjade, physicians will be able to offer NTDT patients a
treatment option, helping fulfill a critical unmet need."

Thalassemia refers to a diverse group of genetic disorders that affect red blood
cell production, causing anemia. Unlike patients with other types of
thalassemia, those with NTDT syndromes don't require regular transfusions, a
significant cause of chronic iron overload. However, even without transfusions,
NTDT patients still accumulate excess iron through intestinal absorption,
leading to debilitating health complications like liver fibrosis and cirrhosis,
blood clots, bone disease, pulmonary hypertension, and vascular and endocrine
diseases[2],[7].

"For years, Exjade has effectively treated chronic iron overload in transfused
thalassemia patients," said Alessandro Riva, Global Head, Oncology Development
and Medical Affairs, Novartis Oncology. "Now, for the first time, thalassemia
patients who do not receive regular transfusions but suffer the same
debilitating effects from chronic iron overload, have an approved treatment
option."

According to published studies, at least three quarters of a million people
worldwide have NTDT syndromes, although as understanding of the disease
increases it is probable the number will grow[3]-[5]. Because NTDT patients are
not symptomatic at birth, when most thalassemias are diagnosed, they are often
underdiagnosed and undertreated[6]. Many complications associated with chronic
iron overload begin to appear as early as age 10 and become increasingly common
as patients reach their 20s or 30s[8]. Most NTDT patients are of South and
Southeast Asian, Mediterranean or Middle Eastern origin, with immigration
broadening the global prevalence[6],[9].

About the THALASSA Study
The THALASSA trial showed that Exjade at a 10 mg/kg per day starting dose
significantly reduced LIC from baseline by 3.8 mg of iron per gram of liver dry
weight (Fe/g dw) compared to an increase of 0.38 mg Fe/g dw in patients
receiving placebo after 52 weeks of treatment (p<0.001)[1]. The study also
determined that a 10 mg/kg per day dose was superior to a 5 mg/kg per day dose
(p=0.009)[1]. Additional research has also demonstrated Exjade continues to
provide benefit over the longer term, with LIC levels reduced by 7.14 mg Fe/g dw
from baseline after 24 months of treatment[10]. The most common reported adverse
events (at least 5% in any Exjade or placebo group) were nausea, skin rash,
diarrhea and headache[1].

About Exjade
In the US, Exjade is now indicated for the treatment of chronic iron overload in
patients 10 years of age and older with non-transfusion-dependent thalassemia
(NTDT) syndromes and with a liver iron concentration (LIC) of at least 5 mg of
iron per gram dry weight (mg Fe/g dw) and a serum ferritin measurement greater
than 300 micrograms per liter. The basis of this indication is data showing
achievement of an LIC less than 5 mg Fe/g dw after treatment with Exjade. An
improvement in survival or disease-related symptoms has not been established.
Since 2005, Exjade has been approved in the US for the treatment of chronic iron
overload due to blood transfusions in adult and pediatric patients (aged 2 years
and over).

In the European Union (EU), Exjade is an oral iron chelation therapy indicated
for the treatment of chronic iron overload due to frequent blood transfusions
(>=7 ml/kg/month of packed red blood cells) in patients with beta-thalassemia
aged 6 years and older. It is also indicated for the treatment of chronic iron
overload due to blood transfusions when deferoxamine therapy is contraindicated
or inadequate in the following patient groups: patients with beta-thalassemia
major with iron overload due to frequent blood transfusions (>=7 ml/kg/month of
packed red blood cells) aged 2 to 5 years; patients with beta-thalassemia major
with iron overload due to infrequent blood transfusions (<7 ml/kg/month of
packed red blood cells) aged 2 years and older; and patients with other anemias
aged 2 years and older. Exjade is also indicated for the treatment of chronic
iron overload requiring chelation therapy when deferoxamine therapy is
contraindicated or inadequate in patients with non-transfusion-dependent
thalassemia syndromes aged 10 years and older.

Exjade is approved in over 100 countries including the US, Switzerland, Japan
and countries comprising the EU. The approved indication may vary depending upon
the individual country.

Exjade Important Safety Information
Exjade is contraindicated in patients with an estimated creatinine clearance <60
mL/min, with hypersensitivity to the active substance or any of the excipients,
or in combination with other iron chelator therapies. Exjade is not recommended
in patients with severe hepatic impairment.

There have been postmarketing reports of acute renal failure, hepatic failure
and cytopenias. Renal failure requiring temporary or permanent dialysis, renal
tubulopathy and interstitial nephritis have been reported. Upper
gastrointestinal ulceration and hemorrhage, sometimes fatal, have been reported.
Caution should be used in elderly patients due to a higher frequency of adverse
reactions. Exjade is not recommended in patients with a short life expectancy
(e.g., high-risk myelodysplastic syndromes), especially when co-morbidities
could increase the risk of adverse events.

Skin rashes, serious hypersensitivity reactions, decreased hearing and lens
opacities have been reported. The most common adverse reactions are nausea,
vomiting, diarrhea, abdominal pain, rash, non-progressive increases in serum
creatinine, increased transaminases, abdominal distension, constipation,
dyspepsia, proteinuria and headache.  Please visit www.exjade.com for more
information.

Disclaimer
The foregoing release contains forward-looking statements that can be identified
by terminology such as "will," or similar expressions, or by express or implied
discussions 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 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; competition in general; government, industry and general public
pricing pressures; unexpected manufacturing issues; 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 2011, the Group
achieved net sales of USD 58.6 billion, while approximately USD 9.6 billion (USD
9.2 billion excluding impairment and amortization charges) was invested in R&D
throughout the Group. Novartis Group companies employ approximately 127,000
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the world. For more information, please visit www.novartis.com.

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References
1. Taher A, Porter J, Viprakasit V, et al. Deferasirox significantly reduces
iron overload in non-transfusion-dependent thalassemia: 1-year results from
a prospective, randomized, double-blind, placebo-controlled study. Blood.
2012. Published online before print May 15, 2012.
2. Musallam KM, Cappellini MD, Wood JC, et al. Iron overload in non-
transfusion-dependent thalassemia: a clinical perspective. Blood Reviews.
2012:26S:S16-S19.
3. Vichinsky E. Hemoglobin E syndromes. Hematology Am Soc Hematol Educ
Program. 2007;79-83.
4. Weatherall DJ. The definition and epidemiology of non-transfusion-dependent
thalassemia. Blood Reviews. 2012:26S:S3-S6.
5. Vichinsky EP. Changing patterns of thalassemia worldwide. Ann NY Acad Sci.
2005;1054:18-24.
6. Thalassaemia International Federation. The Thalassaemia International
Federation's New Focus: Addressing the Management of Non-Transfusion-
Dependent Thalassaemias (NTDT). Position Paper 5.2. March 20, 2012.
Accessed at:
www.thalassaemia.org.cy/pdf/NTDT_Position_Paper_Final.pdf.
7. Musallam KM, Cappellini MD, Wood JC, Motta I, Graziadei G, Tamin H, Taher
AT. Elevated liver iron concentration is a marker of increased morbidity in
patients with B thalassemia intermedia. Haematologica. 2011
Nov;96(11):1605-12.
8. Taher AT. Age-related complications in treatment-naïve patients with
thalassemia intermedia. Brit J Haematol. 2010;150:486-489.
9. Taher A, Cappellini MD, Musallam KM. Recent advances and treatment
challenges in patients with non-transfusion-dependent thalassemia. Blood.
2012;26S:S1-2.
10. Taher AT, Porter JB, Viprakasit V et al. Deferasirox continues to reduce
iron overload in non-transfusion-dependent thalassemia: a one-year, open-
label extension to a one-year, randomized double-blind, placebo-controlled
study (THALASSA). Poster presented at the 54(th) American Society of
Hematology Annual Meeting and Exposition in Atlanta, GA (8-11 December
2012). Abstract #3258.

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