Once-Yearly Reclast(R) Demonstrates Highly Significant Fracture Risk Reductions In The Treatment Of Postmenopausal Osteoporosis, New Study Shows

New Phase III data presented for the first time demonstrated that the investigational treatment Reclast(R) (zoledronic acid) 5 mg was highly effective in reducing the incidence of bone fracture in women with postmenopausal osteoporosis across the most common fracture sites - hip, spine and non-spine - with sustained effect over three years.¹ Further data demonstrated that postmenopausal osteoporosis patients currently taking oral alendronate can be directly switched to Reclast and maintain beneficial bone effects for a full 12 months after a single dose.² These studies were presented today at the annual meeting of the American Society of Bone and Mineral Research (ASBMR) in Philadelphia.

Postmenopausal osteoporosis (osteoporosis) is a serious condition affecting millions of women worldwide.³ An estimated one out of every two women over age 50 with osteoporosis will suffer an osteoporotic fracture in her lifetime.⁴ Of those women age 65 years or older who fracture a hip, 21% will die within one year.⁵ Reclast is the only once-yearly bisphosphonate treatment being studied for the treatment of osteoporosis.

An interim analysis encompassing 99% of the data from the now completed three-year HORIZON Pivotal Fracture Trial showed that patients treated with Reclast experienced a 70% risk reduction in new spine fractures (p<0.0001) and a 40% risk reduction in hip fractures (p=0.0032) over three years compared to placebo. This met the study's two primary endpoints. Additionally, the study met all secondary endpoints including risk reduction in clinical spine fractures and non-spine fractures.

In the study, the overall incidence of adverse events experienced with Reclast was comparable to placebo. The most common adverse events associated with Reclast were the following post-dose symptoms: fever, muscle pain, flu-like symptoms, headache, and bone pain, the majority of which occurred within the first three days following Reclast administration. The majority of these symptoms resolved within the first three days of the event onset. The incidence decreased markedly with subsequent doses of Reclast. Analysis of key safety parameters, including kidney and jaw safety, found Reclast to be comparable to placebo.¹

"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 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 directly switch to Reclast. In the study, the beneficial effects of alendronate on bone mineral density levels in postmenopausal women were maintained for 12 months after a single infusion of Reclast, and, at 12 months, bone mineral density values for patients randomized to receive Reclast were similar to bone mineral density values for patients randomized to continued treatment with alendronate, meeting the study's primary endpoint. In patients taking Reclast, bone turnover remained within the normal pre-menopausal range at 12 months after an infusion.² The most common adverse events reported in this study were similar to those observed in the pivotal fracture trial.^{1, 2, 6}

Furthermore, two separate studies of women being treated for osteoporosis have shown that a majority preferred a once-yearly infusion to a once-weekly pill.^{7, 8}

"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 In Post-Menopausal Osteoporosis: Study Designs

The Health Outcomes and Reduced Incidence with Zoledronic acid Once yearly (HORIZON) Pivotal Fracture Trial is a multi-national, multi-center, 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. Primary endpoints were incidence of new vertebral fractures and hip fractures at three years compared to placebo. All study participants received elemental calcium (1000 to 1500 mg per day) and vitamin D (400 to 1200 IU per day).

The second Phase III Reclast study presented at ASBMR investigated the safety and efficacy of treating patients with Reclast who were previously taking Fosamax. This randomized, double-blind, double-dummy, multi-center trial compared a single infusion of 5 mg Reclast vs. continuation of therapy with oral alendronate weekly for 52 weeks. The study included postmenopausal women with low bone mineral density (n=225). The women must have been treated with Fosamax for at least one year prior to randomization. The primary endpoint of the study was percent change in lumbar spine bone mineral density from baseline to one year.

About Reclast

Reclast is being studied worldwide in a series of multi-national and multi-center clinical trials program called HORIZON. This clinical development program studies a once-yearly dosing with Reclast for osteoporosis. It also includes studies in the prevention of clinical fractures following a 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 5mg, under the brand name Aclasta(R), has been approved in approximately 50 countries worldwide, including the EU and Canada, for the treatment of Paget's disease. The U.S. Food and Drug Administration (FDA) issued an "approvable letter" for Reclast for the treatment of Paget's disease of the bone 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, is also available under the brand name Zometa(R) for use in other indications.

About Postmenopausal Osteoporosis

Postmenopausal osteoporosis (PMO) is a serious condition affecting millions of women worldwide. Osteoporosis currently affects an estimated 50.7 million people in the UK, France, Germany, Italy, Spain, the USA and Japan.³ Incidence of hip fracture in women is projected to rise by 240% worldwide by 2050, as populations grow and age.⁹