Zoledronic acid

Novel investigational agent found more effective, longer lasting with faster onset of action than current standard treatment

EAST HANOVER, N.J., Aug. 31 /PRNewswire/ -- A head-to-head study published today in The New England Journal of Medicine reports that a single infusion of the investigational bisphosphonate, zoledronic acid 5 mg solution, offers superior efficacy, longer period of remission, and faster onset of action compared to the oral bisphosphonate risedronate (Actonel(R)) in patients with Paget's disease.

Paget's disease is the second most prevalent bone disease after osteoporosis. Affecting more than one million people, the chronic bone disorder is marked by the malfunction of the body's regular bone building process and may result in pain, deformities and fractures.

This pooled analysis of two identical double-blind, active-controlled studies compared a single 15-minute infusion of zoledronic acid 5 mg solution to oral risedronate (30 mg per day for 60 days) in 357 patients with Paget's disease. At six months, nearly all patients receiving one dose of zoledronic acid 5 mg solution were effectively treated. Specifically, 96 percent of patients treated with zoledronic acid 5 mg solution responded compared to 74 percent of patients who received risedronate (p<0.001). Response was measured by a reduction (greater than or equal to 75 percent) or normalization of total serum alkaline phosphatase (SAP) levels, a key bone remodeling marker.

"This study may provide for a new and effective option in the management of Paget's disease by demonstrating that a single dose of 5 mg zoledronic acid is more effective than the current standard of care -- both in time to first response and in normalizing the bone turnover process for longer periods," said lead study author Ian Reid, MD, University of Auckland, New Zealand. "The convenient infusion of zoledronic acid eliminates the need for patients to comply with the strict daily regimen required by oral medications."

A faster onset of action was seen in patients treated with zoledronic acid 5 mg solution. Specifically, these patients showed a shorter median time in reaching first response than those taking risedronate, 64 days versus 89 days, p<0.001, respectively. Additionally, SAP levels were normalized in 89 percent of patients who received zoledronic acid 5 mg solution compared to 58 percent of patients treated with risedronate (p<0.001). The greater response rates seen with zoledronic acid 5 mg solution were independent of age, gender, baseline SAP levels and previous therapy for Paget's disease.

More patients receiving zoledronic acid 5 mg solution also maintained therapeutic responses compared to risedronate after one year. For those patients that responded at the end of six months and entered into the post-trial follow-up for a further six months, there was a loss of therapeutic response in only one out of 113 zoledronic acid-treated patients, compared to 21 out of 82 risedronate-treated patients.

"These study results are impressive because zoledronic acid 5 mg solution has the better response in normalizing serum alkaline phosphatase levels," added study co-author Paul Miller, MD, medical director, Colorado Center for Bone Research. "Additionally, the study showed that the effects of zoledronic acid 5 mg solution last longer and patients respond more quickly compared to the comparator drug."

Overall, the number of patients with adverse events were similar in the zoledronic acid and risedronate groups. The most common adverse events with zoledronic acid 5 mg solution were mild to moderate flu-like symptoms such as muscle aches and low grade fever relating to the infusion, the majority of which occurred within three days of infusion and usually resolved within four days. After three days, adverse events were comparable between the two groups.

About Paget's Disease

Paget's disease of the bone is characterized by a malfunction in the way bone is built up and broken down at the cellular level, which may result in bone pain, osteoarthritis, deformities and fractures. In the normal cycle of bone life, bone breaks down and is replaced by new bone. In Paget's disease, that cycle is disrupted and bone breaks down too quickly and replacement bone is not normal.

About Zoledronic Acid 5 mg Solution

The New Drug Application for zoledronic acid 5 mg solution is currently under review by the U.S. Food and Drug Administration (FDA) for the treatment of Paget's disease. The US Food and Drug Administration issued an "approvable letter" for this product for the treatment of Paget's disease of the bone in March 2005. Novartis is working with the US regulatory agency to gain approval for this indication. Zoledronic acid 5 mg solution received approval for the treatment of Paget's disease in 27 European countries in April 2005 and in Canada in June 2005. In addition, it is being studied worldwide to evaluate its impact on several other bone disorders including osteoporosis, corticosteroid-induced osteoporosis and osteogenesis imperfecta in children.

The foregoing release contains forward-looking statements that can be identified by terminology such as "may," "is being studied," or similar expressions, or by discussions regarding potential regulatory approvals for zoledronic acid, potential new indications for zoledronic acid, or regarding potential future sales of zoledronic acid. Such forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause actual results with zoledronic acid to be materially different from any future results, performance or achievements expressed or implied by such statements. There is no guarantee that zoledronic acid 5 mg solution will be approved by the U.S. Food and Drug Administration or any other regulatory authority for any indication in any market. Neither can there be any guarantee regarding potential future sales of zoledronic acid. In particular, management's ability to ensure satisfaction of any health authorities' requirements is not guaranteed and management's expectations regarding commercialization of zoledronic acid 5 mg solution could be affected by, among other things, additional analysis of zoledronic clinical data; new clinical data; unexpected clinical trial results; unexpected regulatory actions or delays or government regulation generally; the company's ability to obtain or maintain patent or other proprietary intellectual property protection; competition in general; government, industry and general public pricing pressures; and other risks and factors referred to in Novartis AG's current Form 20-F on file with the Securities and Exchange Commission of the United States. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those anticipated, believed, estimated or expected. Novartis is providing the information in this press release as of this date and does not undertake any obligation to update any forward-looking statements contained in this press release as a result of new information, future events or otherwise.

About Novartis

Novartis Pharmaceuticals Corporation researches, develops, manufactures and markets leading innovative prescription drugs used to treat a number of diseases and conditions, including central nervous system disorders, organ transplantation, cardiovascular diseases, dermatological diseases, respiratory disorders, cancer and arthritis. The company's mission is to improve people's lives by pioneering novel healthcare solutions.

Located in East Hanover, New Jersey, Novartis Pharmaceuticals Corporation is an affiliate of Novartis AG. Novartis AG is a world leader in pharmaceuticals and consumer health. In 2004, the Group's businesses achieved sales of USD 28.2 billion and a net income of USD 5.8 billion. The Group invested approximately USD 4.2 billion in R&D. Headquartered in Basel, Switzerland, Novartis Group companies employ approximately 81,400 people and operate in over 140 countries around the world. For further information, please consult http://www.novartis.com/.

Actonel(R) is a registered trademark of P&G Pharmaceuticals, Inc. and Aventis Pharmaceuticals, Inc., a member of the sanofi-aventis Group.

CONTACT: Regina Moran of Novartis Pharmaceuticals Corporation, +1-862-778-5567 (direct), +1-973-476-3643 (mobile), regina.moran@novartis.com

Web site: http://www.novartis.com/

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