Largest-Ever Biopsy Study in Osteoporosis Demonstrates Superior Bone Forming Activity With Protelos(R) (Strontium Ranelate) Versus Bisphosphonates

VALENCIA, Spain, March 24, 2011 - Protelos(R) (strontium ranelate) has significantly greater bone-forming
activity than the commonly prescribed bisphosphonate, alendronate, according
to results of the largest-ever biopsy study in post-menopausal women
presented today at the European Congress on Osteoporosis and Osteoarthritis
(ECCEO011-IOF) in Valencia.[i] Through its unique dual impact on both bone
formation and resorption, Protelos substantially reduces fracture risk, the
primary goal of osteoporosis treatment.

Bone biopsy is the gold standard technique used to examine the effect of
osteoporosis treatments on bone. Bone biopsies involve taking a cylindrical
sample of real bone from the upper part of the pelvis called the iliac crest.
Biopsies allow the identification of non-mineralized (osteoid tissue) and
mineralized subparts of the bone matrix and can be used to measure bone
formation rates and other parameters. Bone formation is measured by examining
mineralizing surface, the proportion of bone surface on which new mineralized
bone is being deposited.

In this international, double blind study of 268 women, Protelos has a
significantly greater effect on mineralizing surface compared to alendronate.
After six months, mineralizing surface, expressed as a percentage of bone
surface (the study's primary endpoint) was 2.94% in Protelos patients
compared to 0.20% in patients receiving alendronate (p<0.001). This superior
effect on bone formation was further amplified after 12 months of treatment.
Protelos also significantly increased both the bone formation rate and the
mineral apposition rate compared to alendronate over six and 12 months of
treatment. The superior bone-forming efficacy of Protelos is linked to its
innovative dual mechanism of action which rebalances bone turnover in favour
of the formation of newer and stronger bone. This is not the case with
bisphosphonates as they have been shown to actually suppress the bone
forming-surface.[ii]

"The results of the study show that Protelos preserves a higher bone
forming activity compared with alendronate," notes study investigator
Professor Roland Chapurlat from the Hôpital Edouard Herriot, Service de
Rhumatologie et Pathologie Osseuse, Lyon, France.

"The bone-forming activity seen here can be attributed to strontium
ranelate's unique mechanism of action which, unlike bisphosphonates that
block bone resorption and formation, combines the dual effects of increasing
or maintaining bone formation and decreasing bone resorption," points out
study investigator Professor PG Ste- Marie from the Centre Hospitalier de
l'Université de Montréal, Canada.

This new trial conducted in 268 post-menopausal women with osteoporosis
is the largest biopsy study ever. It sets a new standard in the assessment of
the effects of different osteoporosis treatments on bone. It is also the
second head to head study in which Protelos demonstrates superiority versus
alendronate. In the previous trial, which used a non-invasive technique (High
Resolution peripheral Quantitative Computerized Tomography), Protelos was
shown to be more effective than alendronate on bone microarchitecture at both
cortical and trabecular level.[iii],[iv]

Over the course of both studies, the occurrence of adverse events was
similar for each treatment group.

Anti-fracture efficacy sustained over 10 years

Better efficacy on bone formation and bone quality are the key
determinants for Protelos and explain its well demonstrated efficacy against
vertebral, non vertebral and hip fractures. [v, vi, vii] It is also the key
determinant explaining why Protelos is the unique treatment which has
recently been shown to have sustained anti-fracture efficacy over 10 years,
making it a first choice of treatment for postmenopausal osteoporotic
women.[viii]

Notes to editors

Osteoporosis - a common, debilitating disease

Osteoporosis is a chronic condition due to decreased bone mass, leading
to reduced bone strength and increased fracture risk. Because women are
particularly susceptible to bone loss after the menopause, by far the most
common form is postmenopausal osteoporosis. The estimated lifetime risk of
wrist, vertebral or hip fracture in Caucasian women over 50 is 45%. The
annual incidence rate of osteoporotic fractures in women is greater than the
combined incidence rates of heart attack, stroke and breast cancer.[iv]
Postmenopausal osteoporosis has a huge impact on healthcare budgets, which
are already expected to double for osteoporosis by the year 2050.

Protelos is marketed by independent French pharmaceutical company,
Servier. It is licensed for the treatment of postmenopausal osteoporosis to
reduce the risk of vertebral and hip fractures. It is currently registered
worldwide and marketed in 72 countries.

Protelos is also sold under the trade names Protos(R), Osseor(R),
Bivalos(R) and Protaxos(R).

References

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[i] Chavassieux P, Brixen K, Zerbini C, et al. Bone formation is
significantly greater in women on strontium ranelate than in those on
alendronate after 6 and 12 months of treatment: histomorphometric analysis
from a large randomized controlled trial. Osteoporos Int. 2011. Abstract.
Presented at the ECCEO Congress, Valencia, Spain, March 2011.

[ii] Ott SM. Long-term safety of bisphosphonates. J Clin Endocrinol Metab
2005; 90:1897-9.

[iii] Rizzoli R, Laroche M, Krieg MA, et al. Beneficial Strontium
ranelate and alendronate have differing effects
on distal tibia bone microstructure in women with osteoporosis. Rheumatol
Int. 2010; 30:1341-1348.

[iv] Rizzoli R, Felsenberg D, Laroche M, et al. Beneficial effects of
strontium ranelate compared to alendronate on bone microstucture - A 2 year
study. Osteoporos Int. 2010; 21(Suppl 1): S28-S29 (Abstract P107).

[v] Meunier PJ, Roux C, Seeman E, et al.The effects of strontium ranelate
on the risk of non vertebral fracture in women with postmenopausal
osteoporosis.N Engl J Med. 2004;350:459-468.

[vi] Reginster JY, Seeman E, De Vernejoul MC, et al. Strontium ranelate
reduces the risk of non vertebral fractures in postmenopausal women
with osteoporosis: TROPOS study. J Clin Endocrinol Metab.
2005;90(5):2816-2822.

[vii] Reginster JY, Felsenberg D, et al. Effect of long term strontium
ranelate treatment on the risk of non vertebral and vertebral fractures in
postmenopausal osteoporosis. Arthritis&Rhum. 2008;58(6):1687-1695.

[viii] Reginster JY, Kaufman JM, Goemaere S et al. Long-term treatment of
postmenopausal osteoporotic women with strontium ranelate: results at 10
years. Osteoporos Int 2010; 21(suppl 5): S665-S666 (Abstract OC4).

For further information, please contact: Ben Stewart, Tonic Life Communications - +44-207-798-9913, ben.stewart at toniclc.com; Laura Craggs, Tonic Life Communications - +44-207-798-9908, laura.craggs at toniclc.com Monica Gounaropoulos, Tonic Life Communications - +44-207-798-9910, monica.g at toniclc.com