22-Aug-2001 - Novartis International AG

FDA approves Novartis' Zometa for the treatment of hypercalcemia of malignancy

Novartis announced today that it has received marketing approval from the US Food and Drug Administration (FDA) for Zometa 4 mg (zoledronic acid for injection), a new generation intravenous bisphosphonate for the treatment of hypercalcemia of malignancy (HCM). HCM is the most common life-threatening metabolic complication associated with cancer.

Clinical trials have demonstrated a statistically significant difference favoring Zometa when compared with the current treatment standard, Aredia® (pamidronate disodium for injection), with respect to the proportion of complete responders. Response was measured by a normalization of corrected serum calcium by day 10. In addition, a 4 mg dose of Zometa offers the convenience of a 15-minute infusion time, as compared with 2 to 24 hours for Aredia.

"We are pleased that the FDA has approved this next generation bisphosphonate as a new treatment option for patients with HCM," said David Epstein, President, Novartis Oncology. "We remain committed to further exploring potential uses of Zometa in treating other cancer-related skeletal complications."

About HCM and Zometa HCM, which is characterized by elevated serum calcium levels, affects more than 10% of all cancer patients and generally occurs late in the course of the disease. HCM occurs when factors made by cancer cells over-stimulate cells called osteoclasts, which accelerate the breakdown of bone (resorption) and release excess calcium into the bloodstream. The resulting excessively high calcium levels overload the kidneys' processing capability. The calcium remains in the blood, leading to potentially life-threatening complications such as dehydration, generalized muscle weakness, fatigue, nausea, vomiting, confusion, coma and even death. HCM appears most frequently in cases of breast cancer, multiple myeloma and non-small-cell lung cancer. It may also occur in head and neck cancer, lymphoma, leukemia, kidney cancer and gastrointestinal cancer.

The clinical data upon which the filing and subsequent approval were based are from two pivotal studies comparing Zometa with Aredia. The two multi-center trials enrolled 287 patients of which 275 met the evaluation criteria. Patients received a single dose of either Zometa 4 mg or Zometa 8 mg and were compared with patients receiving a single dose of Aredia 90 mg. By day 10 of treatment, corrected serum calcium concentrations were normalized in 88% of patients treated with Zometa 4 mg. In comparison, only 70% of patients treated with Aredia 90 mg achieved normalized serum calcium concentrations (p=0.002). The results of this trial were published in the January 2001 issue of the Journal of Clinical Oncology.

In the patients taking Zometa, the median duration of complete response (maintaining normalized calcium levels) was 32 days for Zometa 4 mg, and 18 days for Aredia 90 mg. Time to relapse was 30 days for Zometa 4 mg and 17 days for Aredia 90 mg (p<0.05). There was no difference between the outcomes in the 4 mg versus 8 mg dose of the Zometa arm.

To date, Novartis has received marketing clearances for Zometa for the treatment of HCM in more than 30 other countries, including the EU, Switzerland, Brazil, Canada and Australia.

A supplemental application for Zometa in the treatment of bone metastasis will be filed with the FDA shortly.

Facts, background information, dossiers
  • Novartis
  • Switzerland
  • oncology
  • multiple myeloma
  • lymphoma
  • lung cancer
  • leukemia
  • kidney cancer
  • head and neck cancer
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