Press release from PR Newswire
The Lancet Oncology Publishes Results Of XGEVA® (denosumab) In Patients With Giant Cell Tumor Of Bone
Monday, July 15, 2013
The Lancet Oncology Publishes Results Of XGEVA® (denosumab) In Patients With Giant Cell Tumor Of Bone19:09 EDT Monday, July 15, 2013
Phase 2 Study Reports Safety and Efficacy Results
THOUSAND OAKS, Calif., July 15, 2013 /PRNewswire/ -- Amgen (NASDAQ:AMGN) today announced the Lancet Oncology published planned interim results from an international, open-label, Phase 2 clinical trial that is evaluating XGEVA® (denosumab) in adults and skeletally mature adolescents diagnosed with giant cell tumor of bone (GCTB). The study's primary endpoint is the safety profile of XGEVA. Secondary endpoints are the time to disease progression and the proportion of patients without any surgery at six months.
Based on the investigators' interim assessment, 96 percent (163/169) of patients with surgically unsalvageable GCTB had no disease progression after a median follow-up of 13 months. In those with salvageable GCTB whose surgery was associated with severe morbidity, 74 percent (74/100) of patients required no surgery, and 62 percent (16/26) of patients who had surgery underwent a less morbid procedure than planned. Overall, 72 percent of patients had objective tumor response, per protocol defined criteria, including 25 percent of patients who had an objective tumor response according to modified RECIST(Response Evaluation Criteria In Solid Tumors).
The overall safety profile was found to be consistent with the known safety profile of XGEVA in patients with advanced cancer. Osteonecrosis of the jaw was reported in one percent (3/281) of patients. Hypocalcemia adverse events, all non-serious, were reported in five percent (15/281) of patients. The most common severe adverse events were low phosphate levels, back pain, pain in extremity, depression, musculoskeletal pain and anemia. Serious adverse events were reported in nine percent (25/281) of patients. No treatment-related deaths were reported.
"These results demonstrate the effectiveness of XGEVA in the treatment of giant cell tumor of bone and reinforce our understanding of this rare disease in which RANK Ligand plays a central role," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "XGEVA represents a much needed treatment option for patients who suffer from giant cell tumor of bone that can't be adequately treated with surgery."
GCTB is a rare, osteolytic tumor of the bone that often results in complete destruction of the affected bone, leading to bone fracture, joint dysfunction, deformity or amputation. GCTB typically affects individuals between the ages of 20 to 40.
XGEVA was approved June 13, 2013 by the U.S. Food and Drug Administration (FDA) for the treatment of adults and skeletally mature adolescents with GCTB that is unresectable or where surgical resection is likely to result in severe morbidity. The approval followed a priority review by the FDA, a designation reserved for drugs that offer major advances in treatment, or provide a treatment where no adequate therapy exists. Prior to approval, there had been no approved therapies for GCTB. Surgery is the main treatment option for patients with resectable GCTB. This study is one of two clinical trials on which the FDA approval was based.
XGEVA is a fully human monoclonal antibody that binds to RANK Ligand (RANKL), a protein essential for the formation, function and survival of osteoclasts - the cells responsible for bone resorption. Giant cell tumors of bone consist of stromal cells expressing RANKL and osteoclast-like giant cells expressing RANK receptor. Signaling through the RANK receptor contributes to osteolysis and tumor growth. XGEVA prevents RANKL from activating its receptor, RANK, on the surface of osteoclasts, their precursors and osteoclast-like giant cells.
Study Design In this international, open-label, Phase 2 study, 282 patients with confirmed GCTB and measurable, active disease were divided into three cohorts: patients with surgically unsalvageable GCTB (Cohort 1), patients with salvageable GCTB whose surgery was associated with severe morbidity (Cohort 2), or patients who transferred from a previous XGEVA GCTB study (Cohort 3). All three cohorts received subcutaneous XGEVA 120 mg every four weeks with loading doses on days eight and 15. The primary endpoint is the safety profile of XGEVA in terms of adverse events and laboratory abnormalities. Secondary endpoints of the study vary by cohort and include time to disease progression and the proportion of patients without any surgery at six months.
About Giant Cell Tumor of BoneGCTB is a locally aggressive, benign tumor primarily afflicting younger adults between the ages 20 to 40.1,2 It is estimated that there are approximately 300 to 800 new cases of GCTB annually in the U.S. GCTB is unresectable in approximately 18 to 20 percent of cases.3
Most GCTB tumors occur in the long bones of the body, often around joints, but can also spread to the lungs in rare cases.4,5 Although giant cell tumors are slow growing, patients can experience severe bone pain, soft tissue and joint swelling, loss of mobility and pathologic fracture.4,5 Historically, there have been no approved therapies for GCTB. Surgery is the main treatment option for patients with resectable GCTB; however, surgery, such as amputation, may be associated with significant morbidity.1 These tumors also have a higher recurrence rate within the first three years of surgical intervention.1 When tumors recur, they become more difficult to treat and more likely to spread to other parts of the body.1
About XGEVAXGEVA was approved by the FDA for the prevention of skeletal-related events (SREs) in patients with bone metastases from solid tumors in 2010. XGEVA is not indicated for the prevention of SREs in patients with multiple myeloma. In clinical trials, XGEVA demonstrated a clinically meaningful improvement compared to the previous standard of care in preventing these bone complications.
In 2013, XGEVA was approved by the FDA as the first-and-only treatment for adults and skeletally mature adolescents with GCTB that is unresectable or where surgical resection is likely to result in severe morbidity.
XGEVA Important Safety Information
Hypersensitivity XGEVA is contraindicated in patients with clinically significant hypersensitivity to any component of the product.
Hypocalcemia XGEVA can cause severe symptomatic hypocalcemia, and fatal cases have been reported. Correct pre-existing hypocalcemia prior to XGEVA treatment. Monitor calcium levels and administer calcium, magnesium, and vitamin D as necessary. Advise patients to contact a healthcare professional for symptoms of hypocalcemia.
Osteonecrosis of the Jaw (ONJ) Osteonecrosis of the jaw (ONJ) can occur in patients receiving XGEVA. Patients who are suspected of having or who develop ONJ while on XGEVA should receive care by a dentist or an oral surgeon. In these patients, extensive dental surgery to treat ONJ may exacerbate the condition.
Atypical Subtrochanteric and Diaphyseal Femoral Fracture Atypical femoral fracture has been reported with XGEVA. Causality has not been established as these fractures also occur in osteoporotic patients who have not been treated with anti-resorptive agents. A number of reports note that patients were also receiving treatment with glucocorticoids at the time of fracture. Any patient who presents with thigh or groin pain should be suspected of having an atypical fracture and should be evaluated to rule out an incomplete femur fracture. Interruption of XGEVA therapy should be considered, pending a risk/benefit assessment, on an individual basis.
Embryo-Fetal Toxicity XGEVA can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use highly effective contraception during therapy, and for at least 5 months after with the last dose of XGEVA.
Adverse Reactions The most common adverse reactions in patients receiving XGEVA with bone metastasis from solid tumors were fatigue/asthenia, hypophosphatemia, and nausea. The most common serious adverse reaction was dyspnea.
The most common adverse reactions in patients receiving XGEVA for giant cell tumor of bone were arthralgia, headache, nausea, back pain, fatigue, and pain in extremity. The most common serious adverse reactions were osteonecrosis of the jaw and osteomyelitis.
Please visit www.amgen.com for full prescribing information.
About AmgenAmgen discovers, develops, manufactures and delivers innovative human therapeutics. A biotechnology pioneer since 1980, Amgen was one of the first companies to realize the new science's promise by bringing safe, effective medicines from lab to manufacturing plant to patient. Amgen therapeutics have changed the practice of medicine, helping people around the world in the fight against serious illnesses. With a deep and broad pipeline of potential new medicines, Amgen remains committed to advancing science to dramatically improve people's lives. For more information, visit www.amgen.com and follow us on www.twitter.com/amgen.
Forward-Looking StatementsThis 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 Securities and Exchange Commission (SEC) reports filed by Amgen, including Amgen's most recent annual report on Form 10-K and any subsequent periodic reports on Form 10-Q and Form 8-K. Please refer to Amgen's most recent Forms 10-K, 10-Q and 8-K for additional information on the uncertainties and risk factors related to our business. Unless otherwise noted, Amgen is providing this information as of July 15, 2013, and expressly disclaims any duty to update information contained in this news release.
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 product liability claims. If we fail to meet the compliance obligations in the corporate integrity agreement between us and the U.S. government, we could become subject to significant sanctions. 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 payers, 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 relating to new indications for our products is preliminary and investigative and is not part of the labeling approved by the U.S. Food and Drug Administration (FDA) for the products. The products are not approved for the investigational use(s) discussed in this news release, and no conclusions can or should be drawn regarding the safety or effectiveness of the products for these uses. Only the FDA can determine whether the products are safe and effective for these uses. Healthcare professionals should refer to and rely upon the FDA-approved labeling for the products, and not the information discussed in this news release.
CONTACT: Amgen, Thousand OaksChristine Regan, 805-447-5476 (media)Arvind Sood, 805-447-1060 (investors)
1 Thomas D, Henshaw R, Skubitz K, et. al. Denosumab in patients with giant-cell tumour of bone: an open-label, phase 2 study. Lancet Oncol. 2010;11:275?280.2 MeSH Descriptor Data. National Library of Medicine - Medical Subject Headings website. http://www.nlm.nih.gov/cgi/mesh/2011/MB_cgi?mode=&term=Giant+Cells. Accessed June 24, 2013.3 Thomas DM, Skubitz KM. Giant cell tumour of bone. Current Opinion in Oncology. 2009;21:338-344.4 Bone Cancer. American Cancer Society website. http://www.cancer.org/Cancer/BoneCancer/DetailedGuide/bone-cancer-what-is-bone-cancer. Accessed June 24, 2013.5 Giant Cell Tumor of Bone. American Academy of Orthopaedic Surgeons website. http://orthoinfo.aaos.org/topic.cfm?topic=a00080. Accessed June 24, 2013.