Abstract
On June 23, 2020, Prolia(®) (denosumab) was approved by the National Medical Products Administration (NMPA) in the People's Republic of China as the first monoclonal antibody for the treatment of postmenopausal women with osteoporosis at high risk of fractures. Its brand name in Chinese is , a transliteration from the English name "Prolia", which has an implied meaning of "to give strength to everyone"- a suitable name for a potent anti-resorptive therapy. The approval was supported by a novel marketing authorization application (MAA) that included data from Prolia's global clinical trial program establishing favorable efficacy and safety, augmented by results from a real-world evidence (RWE) study confirming the effectiveness and safety of Prolia in clinical practice within Taiwan and Hong Kong. Key constructs for this registration-quality RWE study included the fit-for-purpose assessment of data quality, methodology and quantitative assessment of potential biases, good practices of study conduct, and reproducibility of results. Using data from clinical practice in Taiwan and Hong Kong to evaluate the benefits versus risks of Prolia treatment in ethnic Chinese women with postmenopausal osteoporosis, the RWE study results for effectiveness were comparable to efficacy demonstrated in the global clinical trial program and results for safety were consistent with the incidence observed in global post-marketing safety studies. While RWE is often used to monitor postmarket safety of drug products, support health insurance coverage decisions, and inform clinicians on real-world use of medicines, it has not been widely used to support regulatory approval for new medicines in lieu of clinical bridging studies in countries where such studies are required. Well-conducted registrational RWE studies can play a pivotal role in complementing the totality of evidence presented in an MAA. The benefits of such an approach include avoiding the collection of additional placebo-controlled trial data in populations where adequate ethnic characterization of efficacy, effectiveness, and safety may already exist from postmarketing sources, and accelerate access for patients to innovative medicines in important regions. Here, we describe a regulatory case study of a novel MAA incorporating RWE that provided important evidence to confirm the benefit:risk of a new drug and facilitated a label expansion to a new patient population.