Henlius Received Acceptance Notification for Clinical Trial Application from NMPA for its Denosumab Biosimilar HLX14
Shanghai, China, March 9, 2020 – Shanghai Henlius Biotech, Inc. (2696.HK) announced that an investigational new drug (IND) application has been accepted by the National Medical Products Administration (NMPA) for HLX14, a Denosumab biosimilar independently developed by Henlius, indicated for the treatment of postmenopausal women with osteoporosis at high risk for fracture.
HLX14 can prevent RANKL/RANK mediated bone-related diseases
HLX14, a recombinant anti-RANKL (receptor activator of nuclear factor kappa B ligand) human monoclonal antibody (mAb) injection, is a biosimilar of Denosumab (Trade Name: Prolia®) developed in accordance with Biosimilar Guidelines. HLX14 can specifically bind to RANKL and block the interaction between RANKL and RANK, which is expressed on the surface of osteoclasts, thus inhibiting RANKL/RANK-mediated differentiation, maturation and activation of osteoclasts, thereby reducing bone resorption and the incidence of skeletal-related events.
Several studies have shown the similarity between HLX14 and its original drug
Currently, the original drug of HLX14, Denosumab has been approved in the United States and the European Union, for the prevention of skeletal-related events in patients with multiple myeloma and in patients with bone metastases from solid tumors, as well as for the treatment of patients with giant cell tumor of bone and patients with osteoporosis at high risk for fracture. Denosumab can increase the bone density and reduce the risk of fracture for these patient populations. In China, Denosumab has already been approved to treat giant cell tumor of bone that is unresectable or where surgical resection is likely to result in severe morbidity, while the other indications like osteoporosis have not been approved. Developed in accordance with Biosimilar Guidelines and via step-by-step comparison , HLX14 was proved to be in high similarity with Denosumab in preclinical pharmacology, toxicology and pharmacokinetic studies.
Increasing medical needs endow HLX14 a broad market prospect
Nowadays, the serious problem of osteoporosis is arising throughout the world. Among all countries, China has the largest population that is suffering from osteoporosis, which mainly occurs in postmenopausal women and elderly people. Health problems caused by osteoporosis, like facture, can result in significant loss of quality of life. Nonetheless, the percentage of patients with osteoporosis that have received standardized treatment is relatively low. With the increasing patient number and improved diagnosis of osteoporosis in China, the huge unmet medical needs in the treatment of osteoporosis are urgently to be addressed.
The original drug of HLX14, Denosumab, can also be used in the treatment of bone metastasis from solid tumors. Bone is a frequent site of metastases in cancer patients, but the overall incidence of bone metastasis is not known. The relative incidence of bone metastasis by type of tumor, in patients with advanced metastatic disease, is: 65-75% in BC; 65-75% in prostate; 60% in thyroid; 30-40% in lung; 40% in bladder; 20-25% in renal cell carcinoma and 14-45% in melanoma. Another indication of Denosumab is giant cell tumor of bone, which is a benign but usually aggressive neoplasm of bone. Globally, giant cell tumor accounts for 4% to 5% of primary bone tumors. Compared with western population, the incidence of giant cell tumor is relatively higher in Chinese population, accounting for 20% of primary bone tumors. Despite the fact that most giant cell tumors are benign, without proper treatment, they often causes serious damage of the affected bone and can finally result in bone fracture, joint dysfunction or even amputation.
The development of HLX14 expands Henlius’ portfolio to cover more disease areas
Henlius actively implements its product development strategy and the product portfolio covers several advanced mAb biosimilar candidates with near-term commercialization possibility. Following HLX01(汉利康), the first approved biosimilar in China, HLX03 (adalimumab injection) and HLX02 (trastuzumab for injection) are now having their NDA under priority review by the NMPA. Remarkably, the Marketing Authorization Application for HLX02, the first biosimilar developed in China to enter a global multi-center phase 3 clinical trial, was accepted to review by EMA in June 2019. The development of HLX14 is an active attempt of Henlius in advancing forward products in the field of osteoporosis and will help the company to further expand portfolio to cover more disease areas.
On top of biosimilar, Henlius has built an extensive pipeline in bio-innovative and combination therapy. While quickly driving clinical studies of novel products in different countries and areas, Henlius is also actively diversifying versatile in-house combination therapy portfolio with a focus on anti-PD-1/PD-L1 mAbs to capture future immuno-oncology opportunities. Looking forward, Henlius will continue to advance the development of innovative biologics by virtue of its established and integrated innovation platform, underscoring its long-term commitment to providing affordable and effective therapies for patients worldwide.
Henlius (2696.HK) is a leading biopharmaceutical company in China with the vision to offer high-quality, affordable and innovative biologics for patients worldwide with a focus on oncology and autoimmune diseases. Since its inception in 2010, Henlius has built an integrated and efficient global R&D platform with key facilities in Shanghai, Taipei and California. The three R&D centers closely collaborate with each other to ensure a highly productive and cost-efficient R&D process. Starting from biosimilar, Henlius presses forward with novel mAb products and immuno-oncology combination therapies with proprietary anti-PD-1 and PD-L1 mAbs as backbone. Henlius establishes a diversified product pipeline of biosimilars, bio-innovative drugs and combination therapies, and builds an integrated platform covering the whole product lifecycle including R&D, commercial-scale production and commercialization. On September 25, 2019, Henlius was listed on the Main Board of the Stock Exchange of Hong Kong Limited with the stock code: 2696.HK.
 Romas E. Clinical applications of RANK-ligand inhibition. Intern Med J 2009;39:110–6.
 Globaldata disease report, 2018中国骨质疏松流行病学调查
 Lin X, Xiong D, Peng Y-Q, et al. Epidemiology and management of osteoporosis in the People’s Republic of China: current perspectives. Clin Interv Aging. 2015;10:1017–1033.
 Macedo F, Ladeira K, Pinho F, et al. Bone metastases: an overview[J]. Oncology reviews, 2017, 11(1).
 Mendenhall WM, et al. Am J Clin Oncol. 2006;29:96-99.
 Hoch B. Inwards C, Sundaram M, et al. Multicentric giant cell tumor of bone. Clinicopathologic analysis of thirty cases. J Bone Joint SurgAm, 2006, 88(9):1998-2008.
 Szendroi M. Giant-cell tumor of bone. J Bone Surg Br, 2004,86(1):5-12.