Single dose of Zoledronic acid yields significantly higher, faster response rates than standard Paget's disease therapy

Main Category: Public Health
Article Date: 18 May 2004 - 0:00 PDT

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One 15-minute infusion of the intravenous bisphosphonate zolendronic acid more rapidly reduced the biochemical markers of bone turnover in patients with Paget's disease than was seen in a head-to-head comparison with the oral treatment risedronate (95% vs. 75% response rate). These findings are according to data presented at the annual meeting of the World Congress on Osteoporosis (WCO) in Brazil.

The data, from the landmark HORIZON (Health Outcomes and Reduced Incidence with Zoledronic Acid ONce Yearly) Clinical Development Program, provide the basis for a marketing application recently submitted by Novartis Pharma AG to the European Agency for Evaluation of Medicinal Products (EMEA) in the European Union, for the use of zoledronic acid as a treatment for Paget's disease. This is the first filing for the use of zoledronic acid in a benign metabolic bone disease.

"The availability of bisphosphonates in recent years has revolutionized the treatment of Paget's disease," said Paul D. Miller, MD, clinical professor of medicine and medical director of the Colorado Center for Bone Research, the lead investigator of the study. "These findings suggest that a single infusion of zoledronic acid may offer a fast, effective medication with very convenient dosing. This is extremely good news for patients."

The randomized, double-blind, active-controlled trial showed that in patients with Paget's disease, one 15-minute infusion of zoledronic acid 5 mg generated a therapeutic response in 95% of patients, compared with 75% of patients taking 30 mg/day of oral risedronate, for 60 days (P<0.001). At the six-month follow-up, serum alkaline phosphatase (SAP) levels, a key marker for bone turnover, were normal in 89% of zoledronic acid patients, compared with 56% of risedronate patients (P<0.001). The primary endpoint was therapeutic response at six months, defined as 75% reduction in, or normalization of, SAP, a standard measure of bone turnover.

Additional information about Paget's disease

Paget's disease of bone (also called osteitis deformans) is a painful and chronic disorder of bone metabolism, the biochemical process by which the skeletal system replenishes itself. In Paget's disease, accelerated breakdown and formation of bone produce new bone that is softer and weaker than normal. The disease causes pain, fractures and deformities that can seriously impede a patient's ability to partake in routine activities of daily living. Paget's disease can affect any part of the skeletal system, most commonly the skull, the spine and the bones of the arms, legs and pelvis. Complications of Paget's disease, the most common bone disease after osteoporosis, can include arthritis, bowing of the limbs and, if the disease affects the skull, hearing loss. Standard treatment for the disorder is primarily palliative (intended to reduce severity and ease symptoms) rather than curative.

"We are very pleased with the dramatic results we've seen so far with zoledronic acid," said Joerg Reinhardt, Head of Pharma Development, Novartis Pharma AG. "To be able to offer a convenient, single-dose treatment for potentially painful and debilitating metabolic bone diseases such as Paget's disease would represent a tremendous step forward for patients."

About The HORIZON Clinical Development Program

The HORIZON Clinical Development Program is the first to study a single-dose regimen for sustaining benefits of six months or longer in Paget's disease and once-yearly dosing for osteoporosis. The HORIZON program includes studies in postmenopausal osteoporosis for prevention of spine and hip fractures, the prevention of clinical fractures following a hip fracture in men and women, and the treatment of osteogenesis imperfecta in children. Worldwide, approximately 10,000 patients, in more than 200 trial centers, on four continents, are enrolled in the HORIZON program, one of the most comprehensive drug evaluation programs ever undertaken in the area of metabolic bone diseases.

This release contains certain forward-looking statements relating to the Company's business, which can be identified by the use of forward-looking terminology, such as "findings suggest," "may offer," "would represent," or similar expressions, or by or by express or implied statements regarding the potential for regulatory approvals to market zoledronic acid for treatment of Paget's disease or any other metabolic bone diseases in any market, or regarding potential future revenues from zoledronic acid from such indications. 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 can be no guarantee that zoledronic acid will be approved for marketing in any jurisdiction for treatment of Paget's disease or any other metabolic bone disease, or that zoledronic acid will achieve any particular sales levels. Any such results can be affected by, among other things, uncertainties relating to product development, including the results of the ongoing HORIZON clinical trial and other such trials, regulatory actions or delays or government regulation generally, the ability to obtain or maintain patent or other proprietary intellectual property protection, increased government pricing pressures and competition in general, as well as factors discussed in the Company's Form 20-F filed with the Securities and Exchange Commission. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those described herein as 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 AG (NYSE: NVS) is a world leader in pharmaceuticals and consumer health. In 2003, the Group's businesses achieved sales of USD 24.9 billion and a net income of USD 5.0 billion. The Group invested approximately USD 3.8 billion in R&D. Headquartered in Basel, Switzerland, Novartis Group companies employ about 78,500 people and operate in over 140 countries around the world.

For further information please consult http://www.novartis.com