Zometa(r) (Zoledronic Acid) Plus Chemotherapy Significantly Improved Overall Survival in a UK Phase III Study of Newly Diagnosed Multiple Myeloma Patients Compared to Oral Clodronate

This Release is Intended for UK Media Only

FRIMLEY, England, June 5, 2010 -

    - Data show zoledronic acid, a bisphosphonate, provided significant
      clinical anticancer benefit and significantly reduced risk of skeletal-
      related events(1,2)

    - Overall survival advantage observed with zoledronic acid plus
      chemotherapy versus oral clodronate plus chemotherapy is independent of
      skeletal-related event benefit(1)

    - Results from a separate five-year follow-up study of hormone
      receptor-positive premenopausal early breast cancer patients showed
      significant improvement in progression-free survival with zoledronic
      acid in this patient population(2)

New data to be presented tomorrow at the 46th Annual Meeting of the American
Society of Clinical Oncology (ASCO) in Chicago, IL, from the Myeloma IX study,
show that zoledronic acid plus first-line chemotherapy significantly improved
overall survival for newly diagnosed multiple myeloma patients by 16%
(P=0.0118) and progression-free survival by 12%, (P=0.0179) compared to oral
clodronate plus first-line chemotherapy(1). The 5.5 month survival
improvement demonstrated by zoledronic acid in this study of nearly 2,000
UK patients was independent of the drug's effect on bone complications (
also known as skeletal-related events or SREs)(1). Zoledronic acid was
significantly superior to oral clodronate in the prevention of bone
complications associated with multiple myeloma, reducing the relative risk
of SREs 24% more than clodronate (P=0.0004)(1).

Zoledronic acid is licensed in the UK for the prevention of bone
complications (skeletal-related events, or SREs) in multiple myeloma and
across a broad range of metastatic cancers (breast, prostate, lung and
other solid tumours) involving bone, as well as for the treatment of
hypocalcaemia of malignancy (HCM)(3).

"This is the first time we have seen in a large, phase III independent
study that zoledronic acid plus chemotherapy significantly improves
survival in patients with myeloma." said Eric Low, Chief Executive of
Myeloma UK. "This is extremely encouraging news for the 4,000 patients who
are diagnosed with myeloma in the UK each year and the results suggest that
zoledronic acid has the potential to help myeloma patients live longer."

Other zoledronic acid data presented at ASCO include a five-year follow-
up analysis from the Phase III Austrian Breast & Colorectal Cancer Study
Group 12 (ABCSG-12) trial, which showed that the addition of zoledronic
acid to hormonal therapy following surgery improved disease-free survival
by 32% (HR=0.68 [95%CI 0.51,0.91], P=0.009) in premenopausal women with
hormone receptor-positive (HR+) early breast cancer(2). Data from the ABCSG-
12 study are the basis of the Company's US and European Union regulatory
filings for zoledronic acid in the adjuvant treatment of premenopausal
hormone receptor-positive early breast cancer.

"There is a significant unmet medical need to further reduce the risks
of breast cancer recurrence and women are naturally very concerned about
the possible return or spread of their disease," said Professor Rob Coleman
, Consultant Medical Oncologist at Weston Park Hospital, Sheffield. "These
five-year data are exciting for oncologists and patients alike because they
indicate that adding zoledronic acid to a post-surgical hormonal treatment
regimen for premenopausal women with hormone sensitive breast cancer can
significantly reduce the risk of recurrence."

Notes to Editors

Myeloma IX Study Details

Myeloma IX is a Phase III, prospective, multicentre, randomised,
controlled study to compare intravenous (IV) zoledronic acid (4mg every 3-4
weeks) with oral clodronate (1600 mg daily) in improving survival(4). A total
of 1,960 evaluable patients(1) from the United Kingdom with newly diagnosed
International Staging System (ISS) stage i, ii or iii multiple myeloma
entered either an intensive or non-intensive treatment pathway, determined
on the basis of performance status, informed decision and consent4.
Patients were randomised for type of bisphosphonate therapy and first-line
therapy (induction chemotherapy) on a 1:1 basis(4). Patients in the intensive
treatment pathway (younger/more fit patients where intensive high-dose
treatment (HDT) with stem cell support was considered appropriate) were
randomised to one of four treatment arms to receive either zoledronic acid
or oral clodronate in combination with one of two intensive induction
chemotherapy regimens(4). Patients in the non-intensive pathway (older/less
fit patients where standard dose chemotherapy was considered appropriate)
were randomised to one of four treatment arms to receive either zoledronic
acid or clodronate in combination with one of two non-intensive induction
chemotherapy regimens(4). Following completion of induction and consolidation
therapy, patients in both pathways were randomised to thalidomide
maintenance or no maintenance therapy, also on a 1:1 basis(4).

The primary study endpoints were overall survival (OS), progression
free survival (PFS) and response(4). OS was defined as the length of time
after randomisation to death from any cause(4). PFS was defined as the length
of time from randomisation to disease progression or death(4). Response was
categorised as complete or partial(4). Secondary endpoints included quality
of life, SREs (including bone fractures, radiation to bone, surgery to bone
and/or spinal cord compression), height loss, toxicity (including
thromboembolic events, renal toxicity, hematologic toxicity and graft
versus host disease), proportion receiving bortezomib-dexamethasone as "
early rescue" on induction chemotherapy and proportion receiving bortezomib-
dexamethasone at relapse(4).

At a median follow-up of 3.7 years, risk of death was reduced by 16%
(P=0.0118) and the risk of progression-free survival events fell by 12%
(P=0.0179) with zoledronic acid versus oral clodronate(1). The proportion of
patients who experienced a SRE was reduced by 24% in those receiving
zoledronic acid versus clodronate (27.0% versus 35.3%; P=0.0004)(1). The
survival advantage demonstrated by zoledronic acid was observed in patients
with stage i, ii, iii newly diagnosed multiple myeloma. This survival
advantage was also observed in addition to and independent of the drug's
effect on bone complications(1).

The tolerability profile of zoledronic acid is well-established and
results from this study were found to be consistent with the known profile.
The incidence of osteonecrosis of the jaw (ONJ) in the zoledronic acid and
clodronate treatment arms was 3.5% and 0.3%, respectively(1). Renal
deterioration was reported to be similar between treatment groups(1).

ABCSG-12 Study Details

ABCSG-12 is an open-label, multicentre, Phase III study that enrolled
1,803 premenopausal women with hormone receptor-positive Stage I or II
breast cancer, with fewer than 10 axillary lymph nodes involved(2,5).
Patients were recruited for the study after curative surgery and initiation
of goserelin treatment for ovarian suppression, and randomly assigned into
one of four study groups: (1) anastrozole plus zoledronic acid; (2)
anastrozole alone; (3) tamoxifen plus zoledronic acid; (4) tamoxifen alone.
Zoledronic acid was administered at a dose of 4mg every six months for a
total treatment period of three years and the median follow-up period was
62 months(2,5).

The primary endpoint for all four study arms was disease-free survival(5)
. Recurrence-free survival, overall survival and bone-mineral density were
secondary endpoints(5). Disease-free survival was defined as the length of
time after randomisation during which patients had no local recurrence,
contralateral breast cancer, distant metastasis, secondary carcinoma and/or
death from any cause(5). Recurrence-free survival was defined as the length
of time after randomisation during which patients had no local recurrence,
contralateral breast cancer, distant metastasis and/or secondary carcinoma.
Bone-mineral density was a primary endpoint of the sub-study(5).
Exploratory endpoints included bone metastasis-free survival(5).

At the median follow-up of 62 months, disease-free survival events were
reduced by 32% (P=0.009) with zoledronic acid added to hormone therapy
versus hormone therapy alone(2). In addition, a positive trend was seen in
overall survival with a 34% reduction in the risk of death but this was not
statistically significant (P=0.10)(2). This updated analysis continues to
show no difference between tamoxifen and anastrozole use, but adding
zoledronic acid significantly improves disease-free survival (HR=0.68 for
both arms)(2). Overall, side effects were consistent with known drug
profiles(5). There were no cases of renal failure or confirmed cases of ONJ
in the study(2).

ABOUT ZOMETA (Zoledronic Acid)(3)

Zoledronic acid is indicated for the prevention of skeletal related
events (pathological fractures, spinal compression, radiation or surgery to
bone, or tumour-induced hypocalcaemia) in patients with advanced
malignancies involving bone. An intravenous bisphosphonate, zoledronic acid
is the only licensed bisphosponate to demonstrate efficacy in reducing or
delaying bone complications across a broad range of tumour types such as
breast, prostate, lung and renal cell cancers, in patients with metastatic
disease when administered monthly. Zometa is administered as a 4mg infusion
over at least 15 minutes.

Zoledronic acid is indicated for the prevention of skeletal-related
events (SREs) in patients with advanced malignancies involving bone across
a broad range of tumours. Laboratory research has suggested that zoledronic
acid may also help protect patients from the spread of cancer to other
parts of the body (distant metastatic sites) and help keep patients
recurrence-free.

IMPORTANT SAFETY INFORMATION(3)

Zoledronic acid has been associated with reports of renal insufficiency
. Patients should be adequately rehydrated and have their serum creatinine
assessed prior to receiving each dose of zoledronic acid. Due to the risk
of clinically significant deterioration in renal function, single doses of
zoledronic acid should not exceed 4 mg and the duration of infusion should
be no less than 15 minutes in 100 ml of dilutent. Severe and occasionally
incapacitating bone, joint, and/or muscle pain has been reported in
patients taking bisphosphonates including zoledronic acid. Caution is
advised when zoledronic acid is used in aspirin-sensitive patients, or with
aminoglycosides, loop diuretics and other potentially nephrotoxic drugs.
Zoledronic acid is the same active ingredient as found in Aclasta. Patients
being treated with Zometa should not be treated with Aclasta concomitantly.

In clinical trials, the most commonly reported adverse events included
flu-like syndrome (fever, arthralgias, myalgias, and skeletal pain),
fatigue, gastrointestinal reactions, anaemia, weakness, cough, dyspnoea and
oedema. Zoledronic acid should not be used during pregnancy. Zoledronic
acid is contraindicated in patients with clinically significant
hypersensitivity to zoledronic acid or other bisphosphonates, or any of the
excipients in the formulation of zoledronic acid.

Osteonecrosis of the Jaw (ONJ): ONJ has been reported in patients with
cancer receiving treatment including bisphosphonates, chemotherapy, and/or
corticosteroids. The majority of reported cases have been associated with
dental procedures such as tooth extraction. A dental examination with
appropriate preventive dentistry should be considered prior to treatment
with bisphosphonates in patients with concomitant risk factors. While on
treatment, these patients should avoid invasive dental procedures if
possible. Little data are available to suggest whether discontinuation of
bisphosphonate therapy reduces the risk of ONJ in patients requiring dental
procedures.

For further information please see the summary of product
characteristics.

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 consumer health products. Novartis is the only company
with leading positions in these areas. In 2008, the Group's continuing
operations achieved net sales of USD 41.5 billion and net income of USD 8.2
billion. Approximately USD 7.2 billion was invested in R&D activities
throughout the Group. Headquartered in Basel, Switzerland, Novartis Group
companies employ approximately 98,000 full-time-equivalent associates and
operate in more than 140 countries around the world. For more information,
please visit www.novartis.co.uk.

References

1. Morgan, GJ, et al. Evaluating the effects of zoledronic acid (ZOL)
on overall survival (OS) in patients (Pts) with multiple myeloma (MM):
Results of the Medical Research Council (MRC) Myeloma IX study. 2010 ASCO
Annual Meeting, abstract 8021.

2. Gnant, M, et al. Mature results from ABCSG-12: Adjuvant ovarian
suppression combined with tamoxifen or anastrozole, alone or in combination
with zoledronic acid, in premenopausal women with endocrine-responsibe
early breast cancer. 2010 ASCO Annual Meeting, abstract 533.

3. Zometa. Summary of Product Characteristics.

4. Medical Research Council. Myeloma IX: Myelomatosis therapy trial for
patients of all age groups. Version 3.0. 14 March 2006.

5. Gnant, M, et al. Endocrine Therapy plus Zoledronic Acid in
Premenopausal Breast Cancer. N Engl J Med 2009; 360(7): 679-91.

For more information, please contact: Novartis UK Press Office, Tel: +44(0)1276-698691, Email: pressoffice-UK.phgbfr at novartis.com; Pip Rogan, Red Health, Tel: +44(0)20-7025-6566, Fax: +44(0)207-025-6499, Email: pip.rogan at redconsultancy.com