Novartis Pharmaceuticals Corporation (EAST HANOVER, NJ) announced that phase III data presented at the 28th Annual meeting of the American Society for Bone and Mineral Research (ASBMR), September 15–19, 2006, in Philadelphia, Pa, demonstrated that its investigational, once-yearly bisphosphonate 15-minute infusion treatment, Reclast® (zoledronic acid) 5 mg, was highly effective at reducing the incidence of bone fracture in women with postmenopausal osteoporosis across the most common fracture sites—hip, spine, and nonspine (with the exception of face, fingers, and toes)—with sustained effect over 3 years. Further data demonstrated that postmenopausal osteoporosis patients currently taking oral Fosamax® (alendronate) can be directly switched to Reclast and maintain beneficial bone effects for a full 12 months after a single dose.

An interim analysis encompassing 99% of the data from the now completed 3-year HORIZON Pivotal Fracture Trial showed 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 with placebo. This met the study's two primary endpoints. Additionally, the study met all secondary endpoints including risk reduction in clinical spine fractures and nonspine fractures. In the study, the overall incidence of adverse events experienced with Reclast was comparable with that of placebo, with side effects generally minor and short-lived. Analysis of key safety parameters, including kidney and jaw safety, found Reclast to be comparable with placebo. All study participants received elemental calcium (1000 to 1500 mg/d) and vitamin D (400 to 1200 IU/d).

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

Additional phase III data presented at the meeting from a study of 225 women with osteoporosis demonstrated that patients treated with weekly Fosamax therapy can switch to Reclast. In the study, the beneficial effects of alendronate on bone mineral density (BMD) levels in postmenopausal women were maintained for 12 months after a single infusion of Reclast, and at 12 months BMD values for patients randomized to receive Reclast were similar to those of patients randomized to continued treatment with alendronate, meeting the study's primary endpoint. In patients taking Reclast, bone turnover remained within the normal premenopausal range at 12 months after an infusion.

"We believe once-yearly Reclast may offer advantages for the millions of women suffering from osteoporosis and potentially provide the most comprehensive protection across the most common osteoporotic fracture sites," said James Shannon, MD, Global Head of Development at Novartis Pharma AG.

Reclast is being studied worldwide in a series of multinational and multicenter clinical trials called HORIZON. This clinical development program studies a once-yearly dosing with Reclast for osteoporosis. It also includes studies of the prevention of clinical fractures following hip fracture in men and women, male osteoporosis, corticosteroid-induced osteoporosis, prevention of osteoporosis, treatment of Paget's disease of the bone, and the treatment of osteogenesis imperfecta in children. Approximately 13,000 patients have participated in the ongoing HORIZON program in more than 400 trial centers worldwide. The HORIZON program is one of the most comprehensive drug evaluation programs ever undertaken in the area of metabolic bone diseases.

Zoledronic acid 5 mg, under the brand name AclastaR, has been approved in approximately 50 countries worldwide, including the EU and Canada, for the treatment of Paget's disease. The US FDA issued an "approvable letter" for Reclast for the treatment of Paget's disease in February 2006. 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. Zoledronic acid, the active ingredient of Reclast, also is available under the brand name Zometa® for use in other indications.

— A. Techman