Amgen's Denosumab Receives Conditional NMPA Approval for Giant Cell Tumor of Bone with Post-Approval Clinical Studies Planned in China

Image from the official website of the National Medical Products Administration

On May 22, 2019, the National Medical Products Administration announced the conditional approval of the import registration application for Denosumab Injection. This drug is indicated for the treatment of giant cell tumor of bone in adults and skeletally mature adolescents whose tumors are unresectable or where surgical resection is likely to result in severe morbidity.

Giant Cell Tumor of BoneGiant cell tumor of bone (GCTB) is an extremely rare and rapidly progressive primary bone tumor characterized by abundant expression of the receptor activator of nuclear factor kappa-B ligand (RANKL). It typically presents as eccentric, osteolytic lesions in the metaphysis and epiphysis of long bones, or in the spine and sacrum. The lesions are highly vascularized and aggressive, with ill-defined margins and a wide transition zone. Mononuclear stromal cells expressing RANKL constitute the neoplastic component of GCTB. According to current hypotheses, these cells recruit osteoclast-like giant cells, thereby driving the tumor’s aggressive osteolytic activity.

Denosumab is the first RANKL monoclonal antibody approved for marketing worldwide, developed by Amgen. This drug is a fully human monoclonal IgG2 antibody against RANKL, exhibiting high affinity and specificity for both soluble and transmembrane forms of human RANKL. In patients with giant cell tumor of bone, denosumab’s inhibition of RANKL secreted by the tumor stromal components significantly reduces or eliminates osteoclast-like tumor-associated giant cells. Consequently, bone lysis is reduced, progression of the giant cell tumor is slowed, and the proliferative stroma is replaced by dense, non-proliferative, differentiated woven new bone, thereby improving clinical outcomes.

As a targeted therapy for giant cell tumor of bone, denosumab has the potential to become an important treatment option addressing the unmet medical needs in this disease. This product’s import registration application in China, exempt from local clinical trials, is supported by overseas clinical data, with all primary supportive clinical data provided by the applicant obtained outside of China. It is understood that Amgen will continue to conduct clinical studies in China after product approval and will develop and strictly implement a risk management plan.

On November 1, 2018, the Center for Drug Evaluation (CDE) officially released the first batch of 40 overseas new drugs in urgent clinical need, with denosumab included on the list. In accordance with CDE requirements, these drugs are exempt from domestic clinical trials and can directly apply for market approval, while benefiting from a specialized channel to expedite review. On October 26, 2018, the marketing application for denosumab was accepted by the CDE and entered the priority review process. To date, the National Medical Products Administration has approved 14 varieties listed in the first batch of overseas drugs in urgent clinical need.

Source: Official Website of the National Medical Products Administration, Insight Pharmaceutical Intelligence Bureau