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
This news release contains forward-looking statements that are based on
management's current expectations and beliefs and are subject to a number of
risks, uncertainties and assumptions that could cause actual results to differ
materially from those described. All statements, other than statements of
historical fact, are statements that could be deemed forward-looking
statements, including estimates of revenues, operating margins, capital
expenditures, cash, other financial metrics, expected legal, arbitration,
political, regulatory or clinical results or practices, customer and
prescriber patterns or practices, reimbursement activities and outcomes and
other such estimates and results. Forward-looking statements involve
significant risks and uncertainties, including those discussed below and more
fully described in the
No forward-looking statement can be guaranteed and actual results may differ materially from those we project. Discovery or identification of new product candidates or development of new indications for existing products cannot be guaranteed and movement from concept to product is uncertain; consequently, there can be no guarantee that any particular product candidate or development of a new indication for an existing product will be successful and become a commercial product. Further, preclinical results do not guarantee safe and effective performance of product candidates in humans. The complexity of the human body cannot be perfectly, or sometimes, even adequately modeled by computer or cell culture systems or animal models. The length of time that it takes for us to complete clinical trials and obtain regulatory approval for product marketing has in the past varied and we expect similar variability in the future. We develop product candidates internally and through licensing collaborations, partnerships and joint ventures. Product candidates that are derived from relationships may be subject to disputes between the parties or may prove to be not as effective or as safe as we may have believed at the time of entering into such relationship. Also, we or others could identify safety, side effects or manufacturing problems with our products after they are on the market. Our business may be impacted by government investigations, litigation and products liability claims. We depend on third parties for a significant portion of our manufacturing capacity for the supply of certain of our current and future products and limits on supply may constrain sales of certain of our current products and product candidate development.
In addition, sales of our products are affected by the reimbursement policies imposed by third-party payors, including governments, private insurance plans and managed care providers and may be affected by regulatory, clinical and guideline developments and domestic and international trends toward managed care and healthcare cost containment as well as U.S. legislation affecting pharmaceutical pricing and reimbursement. Government and others' regulations and reimbursement policies may affect the development, usage and pricing of our products. In addition, we compete with other companies with respect to some of our marketed products as well as for the discovery and development of new products. We believe that some of our newer products, product candidates or new indications for existing products, may face competition when and as they are approved and marketed. Our products may compete against products that have lower prices, established reimbursement, superior performance, are easier to administer, or that are otherwise competitive with our products. In addition, while we routinely obtain patents for our products and technology, the protection offered by our patents and patent applications may be challenged, invalidated or circumvented by our competitors and there can be no guarantee of our ability to obtain or maintain patent protection for our products or product candidates. We cannot guarantee that we will be able to produce commercially successful products or maintain the commercial success of our existing products. Our stock price may be affected by actual or perceived market opportunity, competitive position, and success or failure of our products or product candidates. Further, the discovery of significant problems with a product similar to one of our products that implicate an entire class of products could have a material adverse effect on sales of the affected products and on our business and results of operations.
The scientific information discussed in this news release related to our
product candidates is preliminary and investigative. Such product candidates
are not approved by the
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)