New osteoporosis drug showing efficacy as once-yearly treatment

Study found patients could be switched from alendronate to zoledronic acid and maintain the beneficial effect at 1 year.

New phase 3 trial data shows that an investigational treatment can reduce the incidence of bone fracture over 3 years in women with postmenopausal osteoporosis across the most common fracture sites, including the hip and spine.

Investigators presented an interim analysis encompassing 99% of the data from the now completed HORIZON Pivotal Fracture Trial evaluating Reclast (zoledronic acid 5 mg, Novartis) at the annual meeting of the American Society of Bone and Mineral Research in Philadelphia.

The HORIZON trial — Health Outcomes and Reduced Incidence with Zoledronic acid Once yearly — is a multinational, multicenter, randomized, placebo-controlled trial of 7,736 women. The study evaluated the potential of a once-yearly infusion of Reclast to decrease the risk of fracture in postmenopausal women with osteoporosis. All patients received elemental calcium (1,000 to 1,500 mg per day) and vitamin D (400 to 1,200 IU per day).

The researchers found that patients treated with Reclast experienced a 70% risk reduction in new spine fractures (P<.0001) and a 40% risk reduction in hip fractures (P=.0032) over 3 years compared to placebo, according to a press release by Novartis announcing the results.

Researchers found an overall incidence of adverse events associated with Reclast was comparable to placebo and most common included fever, muscle pain, flu-like symptoms, headache and bone pain. Such adverse events mainly occurred within the first 3 days following treatment and decreased with subsequent treatments.

Treatment with Reclast also showed a kidney and jaw safety profile similar to placebo, according to the release.

Additionally, a second phase 3 trial found patients currently taking oral alendronate (Fosamax, Merck) could be directly switched to Reclast and maintain the beneficial effects for 12 months after a single dose.

This second trial compared a single infusion of 5 mg Reclast vs. continuation of therapy with oral alendronate weekly for 52 weeks. The study included 225 postmenopausal women with low bone mineral density treated with alendronate for at least 1 year prior to randomization.

"The efficacy and safety data show that for the first time, women may have the option of a once-yearly treatment for osteoporosis," Dennis Black, MD, study steering committee chairman from University of California, San Francisco, said in the release. "The results show that Reclast effectively protects women against fractures including those of the hip, which can be devastating."

Zoledronic acid 5mg, marketed under the brand name Aclasta, has been approved in approximately 50 countries worldwide for treating Paget's disease. The FDA issued an approvable letter for Reclast in February, also for treating Paget's disease. The FDA requested additional data from the ongoing clinical trial program in osteoporosis. Novartis is working with the FDA to gain approval for this indication, according to the press release.

For more information:
Black DM, et al. Effect of once-yearly infusion of Zoledronic Acid 5 mg on spine and hip fracture reduction in postmenopausal women with osteoporosis: the HORIZON pivotal fracture trial. Presented at 28th Annual Meeting of the American Society for Bone and Mineral Research, Sept. 15-19, 2006. Philadelphia.
McClung M, et al. Single infusion of zoledronic acid 5 mg provides sustained benefits in BMD and biomarkers at 12 months in postmenopausal women with low bone mineral density and prior alendronate therapy. Presented at 28th Annual Meeting of the American Society for Bone and Mineral Research. Sept. 15-19, 2006. Philadelphia.
Recker R, et al. Bone histomorphetry demonstrates normal bone remodelling in postmenopausal women with osteoporosis/osteopenia switched from oral alendronate to IV zoledronic acid. Presented at 28th Annual meeting of the American Society for Bone and Mineral Research, Sept. 15-19, 2006. Philadelphia.