Basel, Switzerland, 30 April 2003 - Zometa® (zoledronic acid) treatment of patients with prostate cancer that has spread to bone significantly lowers the risk of debilitating bone complications and delays their onset by a median time of more than five months. In addition, increases in pain scores were consistently lower for patients on Zometa than for those on placebo, according to data presented today during the annual meeting of the American Urological Association (AUA) in Chicago, Illinois, USA.
Research indicates that 65% to 75% of all patients with advanced prostate cancer develop bone metastasis, the spread of cancerous cells from the original tumour to bones. Often, bone is the only site of metastasis in these patients. Complications resulting from bone metastases include, among others, bone pain, pathologic fractures, a need for radiation or surgery to bone, spinal cord compression, change of antineoplastic therapy to treat bone pain and hypercalcaemia. These painful, debilitating complications can significantly impact the daily lives of patients and caregivers. A recently published analysis indicates that skeletal fractures in patients with prostate cancer can correlate with decreased survival. Zometa is the first and only bisphosphonate indicated for prostate-related bone metastases.
"The lives of patients with advanced prostate cancer and complications from bone metastases are often typified by severe pain and an inability to carry out daily activities," said Fred Saad, M.D., lead investigator and Associate Professor of Urology and Director of Urologic Oncology at the Montreal Cancer Institute, University of Montreal, Canada. "These findings demonstrate Zometa may reduce the risk of bone complications and their pain progression. The resulting improvement may reduce the stress and burden both patients and their caregivers experience on a daily basis."
Study Details Design
The multicenter, randomised, placebo-controlled trial was conducted in 643 patients with advanced prostate cancer and at least one site of bone metastasis. Of the 643 patients, 208 completed the 15-month core phase, and 186 of them continued to receive double-blind study medication during an extension phase.
Bone Complications
After 24 months of treatment, only 38% of patients in the Zometa group had experienced a bone complication (also called a skeletal-related event, or SRE). By contrast, 49% of patients in the placebo group (P=0.028) developed SREs.
In addition, when compared to placebo, Zometa significantly delayed the time to the first bone complication, the median time was delayed by more than five months (median, 488 days vs. 321 days for placebo, P=0.009), and also significantly delayed the time to the first pathologic fracture. Zometa also significantly reduced the skeletal-morbidity rate (mean, 0.77 vs. 1.47 events/year for placebo, P=0.005). A skeletal- morbidity rate is the ratio of the number of skeletal complications over a defined period time.
The study also included a multiple event analysis, which showed that Zometa reduced the overall risk of developing an SRE by 36% (hazard ratio= 0.64; 95% confidence interval [CI] 0.49; 0.85; P=0.002). This means that patients' risk of developing one or more complications, such as fractures, while on Zometa was significantly reduced.
Bone Pain
Zometa consistently reduced the rate of pain score increases over the entire 24 months that patients were in the study, as assessed by the Brief Pain Inventory (BPI) at baseline and at six-week intervals. This is the first demonstration of durable effect on bone pain achieved with biphosphonate therapy in patients with prostate cancer metastatic to bone.
About Zometa
Novartis has received marketing authorization for Zometa in more than 60 countries, including the member states of the European Union and the United States, for the prevention of skeletal related events in patients with advanced malignancies involving bone. These malignancies include multiple myeloma, prostate cancer, breast cancer, lung cancer, renal cancer and other solid tumours. Novartis also has received marketing clearance for Zometa in the treatment of tumour-induced hypercalcaemia (TIH), also known as hypercalcaemia of malignancy (HCM), in more than 80 countries throughout the world. To date, it is estimated that more than 300,000 patients worldwide have received Zometa treatment.
Contraindications and Adverse Events
In clinical trials in patients with bone metastases, Zometa had a safety profile similar to other intravenous bisphosphonates. The most commonly reported adverse events in bone metastases clinical trials, regardless of causality with Zometa, included flu-like syndrome (fever, arthralgias, myalgias, skeletal pain), fatigue, gastrointestinal reactions, anaemia, weakness, cough, dyspnoea and oedema.
Zometa is contraindicated during pregnancy, in breast-feeding women and in patients with clinically significant hypersensitivity to zoledronic acid or other bisphosphonates, or any of the excipients in the formulation of Zometa. Zometa and other bisphosphonates have been associated with reports of renal insufficiency. Patients should have serum creatinine assessed prior to receiving each dose of Zometa. Due to the risk of clinically significant deterioration in renal function, single doses of Zometa should not exceed 4 mg and the duration of infusion should be no less than 15 minutes. Since safety and pharmacokinetic data are limited in patients with severe renal impairment, Zometa is not recommended in patients with bone metastases with severe renal impairment. In the clinical studies, patients with serum creatinine >3.0 mg/dL were excluded.
The foregoing release contains forward-looking statements that can be identified by terminology such as "show", "significantly lowers risk," "delays onset," "can significantly impact", "can correlate", "may reduce," or similar expressions, or by discussions regarding potential new indications for Zometa, or regarding potential future sales of Zometa. Such forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause actual results with Zometa to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that Zometa will be approved for any additional indications in any market. Neither can there be any guarantee regarding potential future sales of Zometa. In particular, management's ability to ensure satisfaction of the health authorities' further requirements is not guaranteed and management's expectations regarding commercialization of Zometa could be affected by, among other things, additional analysis of Zometa 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; and other risks and factors referred to in the Company'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 AG (NYSE: NVS) is a world leader in pharmaceuticals and consumer health. In 2002, the Group's businesses achieved sales of USD 20.9 billion and a net income of USD 4.7 billion. The Group invested approximately USD 2.8 billion in R&D. Headquartered in Basel, Switzerland, Novartis Group companies employ about 77 200 people and operate in over 140 countries around the world. For further information please consult http://www.novartis.com.
Research indicates that 65% to 75% of all patients with advanced prostate cancer develop bone metastasis, the spread of cancerous cells from the original tumour to bones. Often, bone is the only site of metastasis in these patients. Complications resulting from bone metastases include, among others, bone pain, pathologic fractures, a need for radiation or surgery to bone, spinal cord compression, change of antineoplastic therapy to treat bone pain and hypercalcaemia. These painful, debilitating complications can significantly impact the daily lives of patients and caregivers. A recently published analysis indicates that skeletal fractures in patients with prostate cancer can correlate with decreased survival. Zometa is the first and only bisphosphonate indicated for prostate-related bone metastases.
"The lives of patients with advanced prostate cancer and complications from bone metastases are often typified by severe pain and an inability to carry out daily activities," said Fred Saad, M.D., lead investigator and Associate Professor of Urology and Director of Urologic Oncology at the Montreal Cancer Institute, University of Montreal, Canada. "These findings demonstrate Zometa may reduce the risk of bone complications and their pain progression. The resulting improvement may reduce the stress and burden both patients and their caregivers experience on a daily basis."
Study Details Design
The multicenter, randomised, placebo-controlled trial was conducted in 643 patients with advanced prostate cancer and at least one site of bone metastasis. Of the 643 patients, 208 completed the 15-month core phase, and 186 of them continued to receive double-blind study medication during an extension phase.
Bone Complications
After 24 months of treatment, only 38% of patients in the Zometa group had experienced a bone complication (also called a skeletal-related event, or SRE). By contrast, 49% of patients in the placebo group (P=0.028) developed SREs.
In addition, when compared to placebo, Zometa significantly delayed the time to the first bone complication, the median time was delayed by more than five months (median, 488 days vs. 321 days for placebo, P=0.009), and also significantly delayed the time to the first pathologic fracture. Zometa also significantly reduced the skeletal-morbidity rate (mean, 0.77 vs. 1.47 events/year for placebo, P=0.005). A skeletal- morbidity rate is the ratio of the number of skeletal complications over a defined period time.
The study also included a multiple event analysis, which showed that Zometa reduced the overall risk of developing an SRE by 36% (hazard ratio= 0.64; 95% confidence interval [CI] 0.49; 0.85; P=0.002). This means that patients' risk of developing one or more complications, such as fractures, while on Zometa was significantly reduced.
Bone Pain
Zometa consistently reduced the rate of pain score increases over the entire 24 months that patients were in the study, as assessed by the Brief Pain Inventory (BPI) at baseline and at six-week intervals. This is the first demonstration of durable effect on bone pain achieved with biphosphonate therapy in patients with prostate cancer metastatic to bone.
About Zometa
Novartis has received marketing authorization for Zometa in more than 60 countries, including the member states of the European Union and the United States, for the prevention of skeletal related events in patients with advanced malignancies involving bone. These malignancies include multiple myeloma, prostate cancer, breast cancer, lung cancer, renal cancer and other solid tumours. Novartis also has received marketing clearance for Zometa in the treatment of tumour-induced hypercalcaemia (TIH), also known as hypercalcaemia of malignancy (HCM), in more than 80 countries throughout the world. To date, it is estimated that more than 300,000 patients worldwide have received Zometa treatment.
Contraindications and Adverse Events
In clinical trials in patients with bone metastases, Zometa had a safety profile similar to other intravenous bisphosphonates. The most commonly reported adverse events in bone metastases clinical trials, regardless of causality with Zometa, included flu-like syndrome (fever, arthralgias, myalgias, skeletal pain), fatigue, gastrointestinal reactions, anaemia, weakness, cough, dyspnoea and oedema.
Zometa is contraindicated during pregnancy, in breast-feeding women and in patients with clinically significant hypersensitivity to zoledronic acid or other bisphosphonates, or any of the excipients in the formulation of Zometa. Zometa and other bisphosphonates have been associated with reports of renal insufficiency. Patients should have serum creatinine assessed prior to receiving each dose of Zometa. Due to the risk of clinically significant deterioration in renal function, single doses of Zometa should not exceed 4 mg and the duration of infusion should be no less than 15 minutes. Since safety and pharmacokinetic data are limited in patients with severe renal impairment, Zometa is not recommended in patients with bone metastases with severe renal impairment. In the clinical studies, patients with serum creatinine >3.0 mg/dL were excluded.
The foregoing release contains forward-looking statements that can be identified by terminology such as "show", "significantly lowers risk," "delays onset," "can significantly impact", "can correlate", "may reduce," or similar expressions, or by discussions regarding potential new indications for Zometa, or regarding potential future sales of Zometa. Such forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause actual results with Zometa to be materially different from any future results, performance or achievements expressed or implied by such statements. There can be no guarantee that Zometa will be approved for any additional indications in any market. Neither can there be any guarantee regarding potential future sales of Zometa. In particular, management's ability to ensure satisfaction of the health authorities' further requirements is not guaranteed and management's expectations regarding commercialization of Zometa could be affected by, among other things, additional analysis of Zometa 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; and other risks and factors referred to in the Company'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 AG (NYSE: NVS) is a world leader in pharmaceuticals and consumer health. In 2002, the Group's businesses achieved sales of USD 20.9 billion and a net income of USD 4.7 billion. The Group invested approximately USD 2.8 billion in R&D. Headquartered in Basel, Switzerland, Novartis Group companies employ about 77 200 people and operate in over 140 countries around the world. For further information please consult http://www.novartis.com.
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