Once-yearly Reclast(R) Significantly Reduced Bone Fractures In Women With Postmenopausal Osteoporosis

A once-yearly treatment of
Reclast(R) (zoledronic acid) Injection significantly reduced the incidence
of all types of osteoporotic bone fractures over three years in women with
postmenopausal osteoporosis. This study, published today in The New England
Journal of Medicine, marks the first time that an osteoporosis treatment
significantly reduced all types of fractures in a single study.



Reclast is a bisphosphonate, a class of drugs used to treat
osteoporosis, the most common metabolic bone disease affecting more than 10
million people in the US(1). An estimated one out of every two women over
age 50 will suffer a broken bone in her lifetime (1).



Unlike other bisphosphonate treatments, where women take daily, weekly
or monthly doses for postmenopausal osteoporosis, Reclast is given as a
once- yearly 15-minute infusion. Reclast is currently under review by the
US Food and Drug Administration (FDA) for the treatment of postmenopausal
osteoporosis.



"Unfortunately, many patients who are prescribed oral therapies stop
treatment or take less than the full dose throughout a full year, which
leads to reduced fracture protection," said Dennis Black, Ph.D., the
study's lead author and professor of epidemiology and biostatistics at the
University of California, San Francisco. "A once-yearly infusion is an
exciting potential treatment option because it offers fracture protection
for a full year with one dose."



Results from the study show that Reclast reduced the frequency of
fractures among the areas of the body that are typically affected by
osteoporosis, including the hip, spine, and wrist. Specifically, a 70
percent reduction was achieved in spine fractures. In the same study, the
risk of hip fractures, which are associated with significant mortality (2),
was reduced by 41 percent. Additionally, the reduction in spine fractures
was sustained over three years (60 percent in year one, 71 percent in year
two, and 70 percent in year three).



"We believe Reclast is an innovative treatment approach for the
millions of women with osteoporosis and provides impressive fracture
reduction, the primary goal of osteoporosis treatment," said James Shannon,
MD, Global Head of Development at Novartis Pharma AG.



About the Pivotal Fracture Trial



The Pivotal Fracture Trial was a Phase III, multi-center, randomized,
placebo-controlled study examining the efficacy and safety of Reclast in
reducing the risk of bone fracture in women with postmenopausal
osteoporosis. The study enrolled more than 7,700 women between the ages of
65 and 89 with postmenopausal osteoporosis in 27 countries. The primary
endpoints of the study were new spine and hip fractures over three years
compared to placebo. Secondary endpoints included reducing the incidence of
non-spine fractures, evaluation of bone mineral density (BMD),
normalization of bone turnover markers, and overall safety.
















In addition to reductions in spine and hip fractures, the study also
demonstrated that Reclast significantly reduced the risk of non-spine, all
clinical, and clinical spine fractures by 25 percent, 33 percent and 77
percent respectively.



Bone mineral density increased significantly in the spine by 6.7
percent and the hip by 6 percent in women on Reclast compared to placebo.



In the study, overall incidence of adverse events experienced with
Reclast was comparable to placebo. The most common post-dose adverse events
with Reclast were fever, muscle pain, flu-like symptoms, headache, and
joint pain, most of which occurred within the first three days following
Reclast administration. The majority of these symptoms resolved within
three days of the event onset. The incidence decreased markedly with
subsequent annual doses of Reclast.



Analysis of key safety parameters, including kidney and bone safety
(including osteonecrosis of the jaw), found Reclast to be comparable to
placebo. There was an increased number of cases of serious atrial
fibrillation observed in the women on Reclast compared to those on placebo
(1.3 percent vs. 0.5 percent). These findings have not been observed in
other clinical studies or in post-marketing experience from over 1.5
million patients treated with zoledronic acid for oncology indications.
Data from a large trial in men and women following hip fracture will
provide additional efficacy and safety data for Reclast. These results will
be available in the second half of 2007.



About Reclast



HORIZON, the ongoing clinical program of Reclast, is one of the most
comprehensive drug evaluation programs ever undertaken in the area of
metabolic bone diseases. Approximately 13,000 patients have participated in
the program in more than 400 centers worldwide. It is the first program to
study a once-yearly dosing regimen for the prevention and treatment of
postmenopausal osteoporosis. Other studies involved in the program include
prevention of fractures following a hip fracture in men and women,
treatment of corticosteroid-induced osteoporosis and male osteoporosis.



Reclast is currently approved by the FDA for the treatment of Paget's
disease of bone, the second most common metabolic bone disorder. Reclast is
the first and only single-dose infusion regimen approved to treat Paget's
disease. Zoledronic acid, under the brand names Reclast or Aclasta(R), is
now approved in more than 50 countries, including the US, Canada and the
countries of the EU.



The active ingredient in Reclast is zoledronic acid, which is also
available under the brand name Zometa(R) (zoledronic acid) Injection for
use in certain oncology indications.



Reclast is also under review by the FDA for the treatment of
postmenopausal osteoporosis. If approved, Reclast will be the first and
only once-yearly bisphosphonate indicated for the treatment of
postmenopausal osteoporosis.



Reclast is contraindicated in patients with hypocalcemia (low blood
calcium), hypersensitivity to zoledronic acid and in women who are pregnant
or are breastfeeding. Reclast contains the same active ingredient found in
Zometa. Patients already being treated with Zometa should not be treated
with Reclast. Hypocalcemia may occur with Reclast therapy. All patients
with Paget's disease should receive 1,500 mg of calcium in divided doses
and 800 IU of vitamin D daily, particularly in the two weeks following
Reclast administration. Reclast is not recommended for use in patients with
severe renal impairment (creatinine clearance