A once-monthly formulation of the bisphosphonate ibandronate was recently approved by the Food and Drug Administration for treating postmenopausal osteoporosis, 2 years after a daily formulation of the drug was approved but never marketed.
Ibandronate, which is being marketed as Boniva by Roche, is the third oral bisphosphonate and the first monthly formulation marketed in the United States for osteoporosis. It was approved in late March.
A 2.5-mg daily formulation was approved in 2003, based on a 3-year study that showed a reduction in vertebral fracture risk, but it was never marketed because of the availability of the more convenient, weekly bisphosphonate formulations, alendronate (Fosamax) and risedronate (Actonel).
Approval of the once-monthly 150-mg formulation of ibandronate was based on a 1-year noninferiority study of 1,602 postmenopausal women. The study showed that bone mineral density (BMD) increases in the lumbar spine in patients on monthly ibandronate were significantly higher than in those on 2.5 mg of ibandronate daily (4.85% vs. 3.86%). BMD increases at other skeletal sites also were “consistently higher” among those on the monthly dose, according to the drug's label.
Approval of the daily formulation was based on a 3-year study of almost 3,000 women with postmenopausal osteoporosis; the risk of having a vertebral fracture was 4.7% among those on ibandronate, vs. 9.6% among those on placebo, a highly significant difference.
Over the past decade, several new choices for osteoporosis treatment and prevention have become available, each a little different from the others, providing more opportunities to individualize therapy, said Ethel Siris, M.D., director of the Toni Stabile Osteoporosis Center at New York-Presbyterian Hospital and the Madeline C. Stabile professor of clinical medicine, Columbia University, New York.
The fracture data in the trials of these three drugs are somewhat different, she observed, noting that in the initial 3-year study, daily ibandronate was found to reduce the vertebral fracture risk “quite substantially” but did not reduce the risk of nonvertebral fractures. Alendronate, on the other hand, has been shown to reduce vertebral and hip fractures, and risedronate has been shown to reduce vertebral and nonvertebral fractures, reflected in approved indications, she added in an interview.
In a subgroup of patients with very low T scores in the initial ibandronate study, there was a reduction in nonvertebral fracture risk among those on 2.5 mg, compared with placebo, but that was a post hoc analysis and not a prespecified end point, she said.
Another difference between ibandronate and the other two oral bisphosphonates is that a patient needs to sit or stand for 1 hour after taking ibandronate, compared with only 1/2 hour for the other two agents, she said.
Dr. Siris, a consultant to the manufacturers of alendronate and risedronate, has served on an advisory board for GlaxoSmithKline, which is copromoting ibandronate with Roche.
The recommended dosage of monthly ibandronate is one 150-mg tablet taken on the same day once a month, swallowed with a 6- to 8-ounce glass of water, while standing or sitting. The patient should then wait 60 minutes before lying down or eating, drinking, or taking other medications (to reduce the risk of esophageal irritation). Esophagitis, the main side effect of bisphosphonates, is reduced with less frequent dosing but can still occur.