General Information

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.

Boniva is supplied as a tablet and as an injection for intravenous use.

Boniva tablets: Take one 150 mg tablet once monthly on the same day each month. Instruct patient to swallow whole tablet with 6-8 oz of plain water only, at least 60 minutes before the first food, beverage, or medication of day. Avoid lying down for at least 60 minutes after taking Boniva. Do not eat, drink (except for water), or take other medication for 60 minutes after taking Boniva.

Boniva injection: 3 mg every 3 months administered intravenously over a period of 15 to 30 seconds. Only administer intravenously by a health care professional. Do not mix with calcium-containing solutions or other intravenously administered drugs. Do not administer more frequently than once every 3 months.

Mechanism of Action

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.

Clinical Trial Results

Treatment Study
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 of treatment.

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%.

Once-Monthly Dosing Study
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 (p=0.002).