First Osteoporosis Study in Patients with Hip Fracture Finds Once-Yearly Aclasta-Reclast Prevents Additional Fractures and Improves Survival
Study of more than 2,100 patients who suffered a hip fracture
shows 35% reduction in subsequent osteoporotic fractures in
Aclasta-treated patients
Results published in The New England Journal of Medicine show 28%
reduction in overall mortality in patients given Aclasta against
those given placebo
Few patients currently receive osteoporosis treatment following a
hip fracture despite high risk of morbidity and mortality[1]
US launch underway under brand name Reclast as a once-yearly
treatment for postmenopausal osteoporosis; Aclasta awaiting formal
EU approval
BASEL, Switzerland, Sept. 18, 2007 - Results of the first-ever
clinical study in patients with osteoporosis who suffered a hip
fracture show that a once-yearly infusion of
Aclasta®/Reclast® (zoledronic acid 5 mg)[*] reduced the
risk of subsequent fractures by 35% compared to patients treated
with placebo.
The study found the risk of death was significantly reduced by 28%
in the Aclasta patient group compared to the placebo group (101 vs.
141 deaths). This is especially important since almost a quarter of
people over age 50 who suffer a hip fracture die within one
year[2]. Despite this significant risk, few patients with hip
fractures are diagnosed and treated for osteoporosis following a
hip fracture[1].
The landmark study, involving more than 2,100 men and women, was
published online today as an early release article in The New
England Journal of Medicine and presented simultaneously at the
annual meeting of the American Society for Bone & Mineral
Research (ASBMR).
Aclasta, which was recently approved in the US under the brand name
Reclast®, belongs to a class of drugs called bisphosphonates
used to treat osteoporosis - the most common metabolic bone disease
affecting more than 200 million people worldwide[3]. Unlike oral
bisphosphonates which are taken daily, weekly or monthly, Aclasta
is given as a once-yearly infusion completed in approximately 15
minutes.
"Unfortunately, at present few people who experience hip fractures
are evaluated and treated for osteoporosis," said Steven Boonen,
senior author of the NEJM publication and Professor of Medicine at
the Leuven University Centre for Metabolic Bone Diseases and
Division of Geriatric Medicine in Belgium.
"This unique study highlights a novel approach to treating
osteoporosis and proves that a once-yearly infusion of Aclasta may
significantly advance the way we treat our patients with
osteoporosis," Dr. Boonen said.
Data from the new study, called the Recurrent Fracture Trial, will
be submitted to regulatory authorities worldwide by the end of 2007
to broaden the treatment indication for Aclasta/Reclast.
"This study builds upon the body of evidence for Aclasta/Reclast
and is the first to show that osteoporosis treatment after a hip
fracture can have a positive impact on the lives of patients," said
James Shannon, MD, Global Head of Development at Novartis Pharma
AG. "Aclasta is an important new treatment option for millions of
people who suffer from the potentially life-threatening
consequences of this condition."
In the Recurrent Fracture Trial, Aclasta significantly reduced the
risk of all types of new clinical fractures by 35% compared to
placebo (92 vs. 139 fractures). The risk of new spine fractures was
reduced by 46% (21 vs. 39 fractures) and new non-spine fractures
(such as hip, wrist, arm, leg, rib) by 27% (79 vs. 107 fractures).
The study was not designed to measure significant differences in
hip fractures, but a trend was seen toward a reduction in new hip
fractures (23 vs. 33 fractures, or a 30% reduction).
Fewer patients who received Aclasta died after suffering a fracture
than those treated with placebo (9.6% vs. 13.3%). This was probably
due to a range of factors, but may have been partly related to the
effect of Aclasta in reducing new fractures in patients who had
previously had a hip fracture. Further investigation is needed to
understand this finding more clearly.
This study further supports the favorable safety profile of
Aclasta. Analysis of key safety parameters, including kidney and
cardiovascular safety (including atrial fibrillation), found
Aclasta to be comparable with placebo. Incidence of renal events
was similar between the Aclasta and placebo groups (6.2% vs. 5.6%
respectively). Atrial fibrillation serious adverse events occurred
in 1.1% of Aclasta-treated patients compared to 1.3% of
placebo-treated patients. No cases of osteonecrosis of the jaw
(ONJ) were seen in the Recurrent Fracture Trial. The most common
adverse events with Aclasta were transient post-dose symptoms such
as fever and muscle pain.
The Recurrent Fracture Trial was an international Phase III study
designed to evaluate the efficacy and safety of Aclasta in
preventing subsequent fractures in men and women aged 50 to 98
following the surgical repair of a low-trauma hip fracture (i.e.
caused by a fall from standing height or less, or equivalent
force).
The primary endpoint of the study was to determine the effect of
Aclasta on new clinical fractures following hip fracture. Secondary
endpoints included the change in bone mineral density (BMD) in the
non-fractured hip; vertebral, non-vertebral and hip fractures; and
pre-specified safety endpoints, including death.
Reclast was approved by the US Food and Drug Administration (FDA)
on August 17, 2007 as the first and only once-yearly treatment for
postmenopausal osteoporosis. In July 2007, the Committee for
Medicinal Products for Human Use (CHMP) issued a positive opinion
recommending approval in the European Union. The European
Commission generally follows the CHMP's recommendations and is
expected to soon issue a decision.
The US and EU regulatory submissions were based on results of the
Pivotal Fracture Trial, involving more than 7,700 women. In this
study, published in The New England Journal of Medicine in May
2007, Aclasta was shown to increase bone strength and reduce
fractures in areas of the body typically affected by osteoporosis,
including the hip, spine and non-spine (i.e. hip, wrist, arm, leg,
rib). Aclasta is the only treatment approved to reduce the risk of
fractures across all these key sites. The study showed that Aclasta
reduced the risk of spine fractures by 70% and hip fractures by
41%[4].
Aclasta is approved in more than 60 countries including the US,
Canada and the EU for the treatment of Paget's disease, the second
most common metabolic bone disorder. Additional studies are ongoing
to examine the use of Aclasta to treat corticosteroid-induced
osteoporosis, male osteoporosis and bone loss in postmenopausal
women with osteopenia.
The active ingredient in Aclasta is zoledronic acid, which is also
available in a different dosage under the brand name Zometa®
(zoledronic acid 4 mg) for use in certain oncology
indications.
Disclaimer
The foregoing press release contains forward-looking statements
that can be identified by the use of forward-looking terminology
such as "can", "have the potential", "provide potential",
"expected", "will", "should", similar expressions or express or
implied discussions regarding potential future regulatory
submissions or approvals with respect to, or future sales of,
Aclasta, Reclast or Zometa. Such forward-looking statements reflect
the current views of Novartis and involve known and unknown risks,
uncertainties and other factors that may cause actual results to be
materially different from any future results, performance or
achievements expressed or implied by such statements. There can be
no guarantee that Aclasta or Reclast will be approved for any
additional indications in the EU, US or any additional markets or
that Aclasta, Reclast or Zometa will reach any particular level of
sales. In particular, management's expectations regarding Aclasta,
Reclast and Zometa could be affected by, among other things,
unexpected regulatory actions or delays or government regulation
generally; unexpected clinical trial results, including additional
analysis of existing clinical data, and new clinical data;
competition in general; government, industry, and general public
pricing pressures; the company's ability to obtain or maintain
patent or other proprietary intellectual property protection; as
well as the additional factors discussed in Novartis AG's Form 20-F
filed 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 described herein as anticipated, believed,
estimated or expected. Novartis is providing this information as of
this date and does not undertake any obligation to update any
forward-looking statements contained in this document as a result
of new information, future events or otherwise.
About Novartis
Novartis AG (NYSE: NVS) is a world leader in offering medicines to
protect health, cure disease and improve well-being. Our goal is to
discover, develop and successfully market innovative products to
treat patients, ease suffering and enhance the quality of life. We
are strengthening our medicine-based portfolio, which is focused on
strategic growth platforms in innovation-driven pharmaceuticals,
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self-medication OTC brands. Novartis is the only company with
leadership positions in these areas. In 2006, the Group's
businesses achieved net sales of USD 37.0 billion and net income of
USD 7.2 billion. Approximately USD 5.4 billion was invested in
R&D. Headquartered in Basel, Switzerland, Novartis Group
companies employ more than 100,000 associates and operate in over
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http://www.novartis.com.
References
[1] Gardner MJ, Brophy RH, Demetrakopoulos D, et al. Interventions
to improve osteoporosis treatment following hip fracture. Journal
of Bone and Joint Surgery. 2005; 87-A: 3-7.
[2] National Osteoporosis Foundation; www.nof.org
[3] Cooper C. Epidemiology of osteoporosis. Osteoporosis Int 1999;9
(Suppl2):S2-8 Available at http://www.iofbonehealth.org/health-professionals/
about-osteoporosis/epidemiology.html. Accessed on September 1,
2007.
[4] Black D, Delmas, S, Eastell R, et al for the HORIZON Pivotal
Fracture Trial. Once-Yearly Zoledronic Acid for Treatment of
Postmenopausal Osteoporosis. NEJM 2007; 356(18):1809-22.
[*] The tradename in the US is Reclast®
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Posted: September 2007
