FDA Approved Drugs » 2005
Medical Areas: Musculoskeletal | Family Medicine
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The following drug information is obtained from various newswires, published
medical journal articles, and medical conference presentations.
Company: Roche / GlaxoSmithKline
Approval Status: Approved May, 2003 -- UPDATED: NEW FORMULATION APPROVED MARCH, 2005
Treatment Area: Osteoporosis
Boniva (ibandronate sodium) is a
nitrogen-containing bisphosphonate that inhibits
osteoclast-mediated bone resorption. In osteoporosis, where
osteoclasts break down bone too quickly, inhibition of this pathway
has been shown to slow bone turnover, leading to not only an
attenuation of turnover but also a mean increase in bone mass.
Boniva is specifically indicated for the treatment and
prevention of osteoporosis in postmenopausal women. The recommended
dose of Boniva is 2.5 mg (oral tablet) once daily.
Boniva is approved as a once-daily oral tablet, with a
recommended dosage of 2.5 mg.
Update: In March 2005, Boniva received
approval in a new formulation, as a once-monthly oral tablet, with
a recommended dosage of 150 mg on the same date each month. This
approval made Boniva the first ever once-monthly oral treatment for
any chronic disease.
FDA approval of Boniva for the treatment of osteoporosis was based
on a three-year, randomized, double blind, placebo-controlled,
multinational pivotal phase III trial, called BONE. The study
enrolled 2,946 post-menopausal women between age 55 and 80 years
with osteoporosis. Subjects were treated with either placebo or one
of two oral ibandronate schedules: daily (2.5 mg) or intermittent
(20 mg) taken every other day for 24 days followed by a
between-dose interval of greater than two months. All participants
received daily oral calcium (500 mg) and vitamin D (400 IU)
supplementation. The main outcome measure was the occurrence of new
radiographically diagnosed fractured of the vertebrae after 3 years
Results showed that 2.5mg daily of ibandronate reduced the risk
of new vertebral fractures by 62% compared with placebo. In
addition, data demonstrated an intermittent (20mg) dose of oral
ibandronate taken every other day for 24 days reduced the risk of
new vertebral fractures by 50% compared with placebo. The
cumulative incidence of vertebral fractures in the placebo group
was 9.6% over three years, 4.7% in the 2.5mg daily group and 4.9%
in the 20mg intermittent group. In the study, ibandronate
demonstrated a favorable tolerability profile, with the most
commonly reported adverse events being upper respiratory tract
infection, back pain, arthralgia, dyspepsia and bronchitis. The
percentage of subjects who withdrew from the study due to adverse
events was approximately 18% in each of the three groups.
Prevention Study FDA approval of Boniva for the prevention of
osteoporosis was based on a randomized, double blind, placebo
controlled, two year trial. The study enrolled 653 postmenopausal
women aged 41 to 82 years of age without osteoporosis. Subjects
were given Boniva at .5 mg, 1.0 mg and 2.5 mg or placebo. All
subjects were given 500 mg of supplemental calcium daily. The
primary endpoint was the change in bone mineral density (BMD) of
the lumbar spine after two years of treatment.
Results showed that treatment with 2.5 mg daily of Boniva
achieved a mean increase in lumbar spine BMD of 3.1% compared with
placebo after two years of treatment. Data also showed that Boniva
(2.5 mg daily) achieved an increase in hip BMD by 1.8%, the femoral
neck by 2.0% and the trochanter by 2.1%.
Update: Once-Monthly Dosing
Approval of the once-monthly dosing formulation was based on a
12-month, double-blind, placebo controlled noninferiority study
which compared the safety and efficacy of the 150 mg once-monthly
dose of Boniva to the approved 2.5 mg once-daily dose. The trial
enrolled 1602 postmenopausal women with low BMD due to confirmed
osteoporosis, who were randomized to receive one of the two
regimens. Primary efficacy data indicated that the once-monthly
dose produced a mean increase in BMD of 4.85%, vs. an increase of
3.86% for the daily dose. This 0.99% relative increase exceeded the
non-inferiority endpoint, establishing the once-monthly
regimen's statistical superiority in improving BMD
Adverse events associated with the use of Boniva may include
(but are not limited to) the following:
Update: Results from a 1 year trial
comparing the safety of once monthly Boniva to the approved daily
regimen produced similar tolerability profiles. Serious events
occurred in 7.1% or subjects in the once-monthly group, compared to
4.8% in the daily group. Overall adverse events which may occur
more often with once-monthly dosing vs. once daily include, but are
not limited to, the following:
Boniva has a high binding affinity for hydroxypatite, a calcium
compound which is part of the mineral matrix of bone. Binding to
the site allows the drug to be taken up by mature osteoclasts
during the resorption process, and it appear to act intracellularly
as an isoprenoid diphosphate lipid analogue, disrupting the
farnesylation and geranylgeranylation of small GTPase signaling
proteins and potentiating selective osteoclast apoptosis.
Muller R, Hannan M, Smith SY,
Bauss F. Intermittent ibandronate preserves bone quality
and bone strength in the lumbar spine after 16 months of treatment
in the ovariectomized cynomolgus monkey. Journal of Bone
Mineral Research. 2004 Nov;19(11):1787-96. Epub 2004 Aug
Rogers MJ. New insights
into the molecular mechanisms of action of bisphosphonates.
Current Pharmaceutical Design.
Coleman RE, Purohit OP, Black C, Vinholes JJ, et
al. Double-blind, randomised, placebo-controlled study of
oral ibandronate in patients with metastatic bone disease.
Annals of Oncology 1999;10:311-16
Pecherstorfer M, Herrmann Z, Body JJ, Manegold C, et
al. Randomized phase II trial comparing different doses of
the bisphosphonate ibandronate in the treatment of hypercalcemia of
malignancy. Journal of Clinical Oncology
Ralston SH, Thiebaud D, Herrmann Z, et al.
Dose-response study of ibandronate in treatment of
cancer-associated hypercalcaemia. British Journal of
For additional information regarding Boniva or osteoporosis,
please visit the Boniva web page.
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