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Denosumab Demonstrates Superiority Over Zometa(R) in Pivotal Phase 3 Head-to-Head Trial in Breast Cancer Patients With Bone Metastases
Denosumab Significantly Delayed the Time to the First Skeletal Related Event
and Significantly Reduced First and Subsequent Skeletal Related Events
Compared to Zometa
First of Three Pivotal Oncology Trials Comparing Denosumab to Zometa in the Advanced Cancer Setting Meets Primary and Secondary Endpoints
THOUSAND OAKS, Calif.,
Overall, the incidence of adverse events and serious adverse events was consistent with what has previously been reported for these two agents. Of note, osteonecrosis of the jaw (ONJ), which had not been observed in previously reported Phase 3 studies with denosumab, was seen infrequently in both treatment groups. There was no statistically significant difference in the rate of ONJ between the two treatment arms. Infectious adverse events were balanced between the two treatment arms, as was overall survival and the time to cancer progression.
"We are extremely pleased with the outcome of this important study, which
shows that denosumab can reduce or delay the serious complications of bone
metastases in breast cancer patients better than the current standard of care,
and with a favorable benefit/risk profile," said
Bone metastases, the spread of tumors to the bone, are a serious concern for advanced breast cancer patients, with incidence rates as high as 75 percent. When cancer spreads to the bone, the growing cancer cells weaken and destroy the bone around the tumor. This damage can result in a number of serious bone complications, collectively called SREs.
Full efficacy and safety data will be submitted for presentation at an upcoming medical meeting in the second half of this year.
This was an international Phase 3, randomized, double-blind study comparing denosumab with Zometa in the treatment of bone metastases in patients with advanced breast cancer. Patients enrolled in the study were randomized in a one-to-one ratio to receive either 120 mg of denosumab subcutaneously every four weeks (Q4W) or Zometa administered intravenously at a dose of 4 mg single, 15 minute infusion every four weeks as per the labeled use.
In clinical trials testing new medications for bone metastases, treatment success has been measured by whether the bone complications, or SREs, caused by the tumor are reduced or delayed. The primary and secondary endpoints of the denosumab bone metastases studies use a composite endpoint of four SREs - fracture, radiation to bone, surgery to bone, and spinal cord compression - to measure the effectiveness of denosumab versus Zometa.
The primary endpoint was to evaluate if denosumab is non-inferior to Zometa with respect to the first on-study SRE in patients with advanced breast cancer and bone metastases. Secondary endpoints were to evaluate if denosumab was superior to Zometa with respect to the first on-study SRE, as well as first-and-subsequent on-study SREs, and to assess the safety and tolerability of denosumab compared with Zometa.
About Denosumab and
Denosumab is the first fully human monoclonal antibody in late stage
clinical development that specifically targets RANK Ligand, the essential
regulator of osteoclasts (the cells that break down bone). With more than
19,000 patients in trials across indications worldwide, the denosumab
development program is the largest ever initiated by
Bone Metastases: Impact and Prevalence
Bone metastases, cancer cells that separate from tumors and migrate to bone tissue where they settle and grow, occur in more than 1.5 million people worldwide.(1) With improvements in cancer care, including earlier diagnosis and new treatment options, leading to increases in survival rates(2), the number of patients developing metastatic disease secondary to a primary cancer is increasing. Bone metastases are a significant problem for patients with certain types of advanced cancer, with incidence rates of nearly 100 percent in myeloma patients and as high as 75 percent in breast and prostate cancer patients.
With bone metastases the growing cancer cells weaken and destroy the bone around the tumor. The damage the tumor has caused to the bone can result in a number of serious complications, collectively called skeletal related events (SREs). These include fracture of a bone, radiation to bone, surgery to bone, or spinal cord compression. All are serious complications for advanced cancer patients.
The economic burden of U.S. patients with bone metastases is significant
and was estimated to be
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ZOMETA is a registered trademark of Novartis Oncology.
*Editors Note: The FDA has provisionally approved the trade name Prolia(TM) for the proposed indications of treatment and prevention of osteoporosis in postmenopausal women, and treatment and prevention of bone loss in patients undergoing hormone ablation for non-metastatic prostate or breast cancer, for which denosumab is administered twice yearly subcutaneously at a 60 mg dose. The Prolia(TM) trade name is only for these indications and may not apply for other indications of denosumab.
(1) Capanna R, Coia LR, Coleman R. et al. eds. Textbook of Bone
Metastases. Hoboken, NJ: Edition:
(2) Mundy GR. Metastasis to bone: causes, consequences and therapeutic opportunities. Nat Rev Cancer. 2002 Aug;2(8):584-93.
(3) Schulman K and Kohles J. Cancer. 2007;109:2334-2342
(4) GVD/Barber ISPOR 2008 Poster; Schulman 2007; Delea et al. 2006
Arvind Sood, 805-447-1060 (investors)