Amgen Launches XGEVA® (Denosumab) for Giant Cell Tumor of Bone in China at Guangzhou Event

Guangzhou, December 13, 2019 /PRNewswire/ -- The Amgen Giant Cell Tumor of Bone Summit, themed “Multidimensional Benefits, Comprehensive Care,” and the launch event for the giant cell tumor of bone indication of XGEVA® were held in Guangzhou, marking the official launch in China of the first innovative therapeutic agent for giant cell tumor of bone that is unresectable or where surgical resection may result in severe functional impairment—XGEVA® (denosumab injection).

Denosumab is the drug recommended for the treatment of giant cell tumor of bone in the “Chinese Evidence-Based Clinical Practice Guidelines for Giant Cell Tumor of Bone”^[1]In November 2018, denosumab was included in China’s first batch of the List of Overseas New Drugs in Urgent Clinical Need, thereby entering the National Medical Products Administration’s (NMPA) expedited review pathway. Less than a year later, in May 2019, denosumab was approved by the NMPA for the treatment of giant cell tumor of bone that is unresectable or where surgical resection may result in severe functional impairment, including adult and adolescent patients with skeletal maturity (defined as having at least one mature long bone and a body weight ≥45 kg).

Giant Cell Tumor of Bone: “The Gluttonous Snake That Eats Bones”  

Giant Cell Tumor of Bone is a histologically benign but often aggressive primary bone tumor.^[2], vividly likened to a "bone-eating Snake." Giant cell tumor of bone predominantly affects young and middle-aged adults aged 20–40 years, with a slightly higher incidence in females, accounting for approximately 55%.^[3]. According to a study on the incidence of giant cell tumor of bone in China, the estimated annual incidence of giant cell tumor of bone in China is 1.49–2.57 cases per million population.^[4]Globally, giant cell tumor of bone accounts for approximately 4%-5% of all primary bone tumors.^[5], more common in China than in European and American populations, accounting for approximately 17.3% of all primary bone tumors^[6]。

Giant Cell Tumor of Bone consists of RANKL-expressing stromal cells and osteoclast-like giant cells expressing the RANK receptor; its pathogenesis involves RANKL overexpression, which drives tumor growth and bone destruction.^[7]RANKL is a transmembrane or soluble protein essential for the formation, function, and survival of osteoclasts; osteoclasts are responsible for bone resorption, thereby regulating the release of calcium from bone. The clinical manifestations of giant cell tumor of bone primarily include dull pain, fractures, functional impairment, as well as swelling and masses. Although most giant cell tumors of bone are benign and rarely fatal, they are frequently disabling; therefore, the harm they cause to patients should not be underestimated.

Denosumab: BlockadeRANKLPathway,Inhibit the "Snake" Action

Denosumab is a human immunoglobulin G2 (IgG2) monoclonal antibody with high specificity and affinity for RANKL. The mechanism of action of denosumab involves binding to RANKL, thereby preventing its activation of RANK on the surface of osteoclasts, osteoclast precursors, and osteoclast-like giant cells. In other words, it attenuates the “growth potential” and “destructive capacity” of the “vicious cycle,” thereby achieving the goals of inhibiting tumor growth and reducing bone destruction.

The approval of denosumab for the treatment indication of giant cell tumor of bone (GCTB) was based on the results of two open-label trials involving patients with recurrent, unresectable GCTB, or those for whom planned surgical resection would likely result in severe functional impairment. The primary analysis results, presented at the 2017 European Society for Medical Oncology (ESMO) Annual Meeting, demonstrated that among patients eligible for surgical resection, 80% experienced improvement following neoadjuvant denosumab therapy: 44% underwent downstaged surgery with reduced functional impact, and 37% avoided surgery altogether. In patients with unresectable tumors, denosumab provided effective long-term disease control, with a 5-year progression-free survival (PFS) rate of 88%.^[8]。

Accelerating Access, Pioneering a New Era in Pharmacotherapy for Giant Cell Tumor of Bone

For a long time, the primary treatment modalities for giant cell tumor of bone (GCTB) have been surgery and other adjuvant therapies (such as radiotherapy, embolization, and pharmacological treatment). As the first drug approved in China for the treatment of GCTB, denosumab has landmark therapeutic significance. Its dual action of inhibiting tumor growth and reducing bone destruction delivers significant clinical benefits and improves quality of life for patients with GCTB that is unresectable or whose resection would result in severe functional impairment.

As a global leader in biotechnology, Amgen has always adhered to the principle of “biology first,” with a mission to serve patients by continuously seeking innovative solutions to benefit patients with severe diseases in China. Denosumab, with its innovative mechanism of action, brings new treatment options and hope to patients suffering from this rare disease who are limited by current therapies, thereby helping them achieve disease control and improve their quality of life. In the future, Amgen will continue to leverage its R&D strengths, accelerating the delivery of more benefits to cancer patients in China and around the world through high-quality clinical development and translational medicine research.

[1] Bone Tumor Professional Committee, Orthopedic Surgeons Branch of Chinese Medical Doctor Association. Clinical Evidence-Based Diagnosis and Treatment Guidelines for Giant Cell Tumor of Bone in China. 2018;11(4):276-287.

[2] Mendenhall WM, et al. Am J Clin Oncol. 2006;29:96-99.

[3] Turcotte RE, Giant cell tumor of bone.[J] . Orthop. Clin. North Am., 2006, 37: 35-51.

[4] Alexander Liede, Rohini K. Hernandez, et al. Epidemiology of benign giant cell tumor of bone in the Chinese population. Journal of Bone Oncology 12 (2018) 96-100.

[5] Hoch B. Inwards C, Sundaram M, et al. Multicentric giant cell tumor of bone. Clinicopathologic analysis of thirty cases. J Bone Joint Surg Am, 2006, 88(9):1998-2008.

[6] Niu X, Xu H, Inwards C Y, et al. Primary Bone Tumors: Epidemiologic Comparison of 9200 Patients Treated at Beijing Ji Shui Tan Hospital, Beijing, China, With 10 165 Patients at Mayo Clinic, Rochester, Minnesota[J]. Archives of Pathology & Laboratory Medicine, 2015, 139(9):1149.

[7] Kim Y, Nizami S, Goto H, Lee FY. Modern interpretation of giant cell tumor of bone: predominantly osteoclastogenic stromal tumor. Clin Orthop Surg. 2012;4:107-116.

[8] E.Palmerini,J-Y.Bly, et al. Long-term efficacy of denosumab in giant cell tumor of bone: Results of an open-label phase 2 study. Annals of Oncology (2017) 28 (suppl_5).