SHANGHAI, CHINA, 29th June, 2023 - EDDING announced that the National Medical Products Administration (NMPA) has approved Mulpleta® (Lusutrombopag Tablets) for the adult patients with chronic liver disease accompany thrombocytopenia who are scheduled to undergo an operation procedure (including diagnostic procedure) (CLD) as an import drug on 27th June.
Currently, therapies for CLD patients with thrombocytopenia are limited and critically needed, the available drugs are expensive and hard to purchase. Expert Consensus on Management of Viral Hepatitis (2021) shows that there are about 70,000,000 cases of Hepatitis B (HBV) infection and 10,000,000 cases of Hepatitis C (HCV) infection in China. Although China has implemented a comprehensive prevention and control strategy based on vaccination and combining prevention and treatment, the rising trend of viral hepatitis has been effectively curbed, but the number of viral hepatitis patients is still significant. The prevention and treatment of chronic liver disease have brought a heavy economic burden to the country and the individual. This requires not only investment at the national level but also the support of social forces.
At present, some available treatments have certain restrictions or limitations. The optimal therapeutic regimen for patients with thrombocytopenia associated with chronic liver disease is expected clinically, and there is an urgent need to increase better efficacy and more treatment options to meet the existing clinical options.
Mulpleta® is an orally bioavailable, small molecule thrombopoietin (TPO) receptor agonist that activates the signal transduction pathway in the same manner as endogenous TPO by acting on the transmembrane domain of the human TPO receptors, to promote the production of platelets. Mulpleta® is safe, convenient to use without injection and titration, and stable efficacy. Furthermore, there are some other advantages such as no drug interactions, no food effects, etc. It is a better option for patients and may cause a change to the treatment of CLD patients with thrombocytopenia.
Lusutrombopag is mainly metabolized by CYP4, with fewer drug interactions and higher safety. Studies on drug interactions showed that lusutrombopag had a low possibility of inhibiting CYP enzymes (CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4/5), and had no inducing effect on CYP1A2, CYP2C9 or CYP3A4. Clinically significant changes in exposure to lusutrombopag were also not observed when combined with cyclosporine (P-gp and BCRP inhibitors) or an antacid containing polyvalent cations (calcium carbonate), and midazolam (CYP3A substrate).
The results of the food influence study showed that the drug exposure of lusutrombopag was not affected by food, and thus it could be taken with or without meals. The dosage and usage of lusutrombopag do not require adjustment of the dosage of administration based on the patient’s platelet level before medication. In addition, according to the clinical data of PLUS-1 and PLUS-2, the efficacy of lusutrombopag in the Japanese patient population was better than that in the European and American patient populations. The platelet transfusion avoidance rate of the patient was 79.2% and 64.8% after 7 days of treatment. Around the 4th day of treatment with lusutrombopag in patients with chronic liver disease, an increase in platelet count can be observed, and is the median time to reach the maximum platelet count 12.0-14.0 days. Lusutrombopag, developed based on Asian metabolic characteristics, has a more promising efficacy in the Chinese patient population. Real-world studies after its overseas marketing showed that the platelet avoidance rate could reach 94%, much higher than the clinical trial data of other oral TPO receptor agonists of the same category.
“Mulpleta® is EDDING’s second innovative drug approved in the past month. Two products were approved successively within 30 days, it means a lot to us”, said Rebecca Xu, Vice President of Clinical Development, EDDING. “Thrombocytopenia is one of the challenges for the current surgeries and treatments, and life threatening in serious cases. Mulpleta® is a TPO receptor agonist with the characteristics of high response, safety and convenience. As a new generation of therapeutic option to increase platelets, it can provide a well-tolerated and effective treatment for patients with severe thrombocytopenia who require invasive surgery. We are very happy to introduce it in China, and hope that in the future, we can provide clinical experts with more treatment options to benefit more Chinese patients.”
Mulpleta® was approved in Japan in September 2015, in the United States in August 2018 and in Europe in February 2019.
In 2019, EDDING and Shionogi & Co., Ltd. reached an exclusive licensing agreement, announced that Shionogi license-out lusutrombopag, a thrombopoietin receptor agonist (brand name in Japan: MULPLETA®) to Edding in the Greater China, including Mainland China, Hong Kong and Macau.
The NMPA’s approval was based on the safety and efficacy data from one Phase 3 clinical trial in China (by EDDING), which is consistent with the data from two Phase 3 trials overseas (L-PLUS 1 and L-PLUS 2 studies). The primary efficacy endpoints and key secondary endpoints of the Phase 3 trial in China are similar to those of the two registration Phase 3 trials in Japan and the world, and there are no new unexpected adverse events (AEs) compared with previous studies in terms of safety.
About EDDING
With the mission of helping people for a healthy life, EDDING has always persisted to linking global life science and technology to China. With over 20 years of intensive exploration and research, it has the clinical research and development capabilities of innovative drugs, high-end production and manufacturing capabilities, and a robust commercial operation network, becoming an integrated pharmaceutical company with a full industrial chain and the vision of "Global for China". EDDING has developed the development strategy strictly in accordance with the Outline of the Healthy China 2030 Plan. It focuses on the core therapeutic areas covering anti-infection, cardiovascular system, respiratory system, blood, etc., where the patient base is large in China, and the diagnosis and treatment rates need to be improved. EDDING keeps on exploring high-quality drugs to meet the potential medical needs in China.
About Chronic Liver Disease (CLD)
Chronic liver disease, especially viral hepatitis, is an important public health problem in China. According to the data released by the Chinese Center for Disease Control and Prevention (CDC), the number of cases of viral hepatitis in Class B notifiable infectious diseases in 2021 ranked first (1,226,165 cases), the number of new hepatitis cases reached 1,236,000 annually and the incidence ranked first, about 86.9/100,000[1]. CLD mainly refers to the general term for liver diseases with liver cell necrosis and slowed liver regeneration as pathological manifestations. Thrombocytopenia is a common complication in patients with CLD. It has been reported that up to about 78% of patients with decompensated cirrhosis have varying degrees of thrombocytopenia, and about 14% are complicated with severe thrombocytopenia. [2, 3]
About Thrombocytopenia (TCP)
The degree of thrombocytopenia is related to the severity of liver disease. The more severe the liver disease, the more severe the thrombocytopenia. Thrombocytopenia increases the risk of clinically significant bleeding, such as cerebral or other internal bleeding, as well as petechiae, purpura, and mucosal hemorrhage. Nowadays, there are about 460,000 people in China suffer from chronic liver disease and require elective surgery [4].
In addition, thrombocytopenia not only refers to a condition in which the number of circulating platelets in the blood is lower than the normal number, but also includes diseases in which platelets cannot function normally, mainly including idiopathic thrombocytopenic purpura (ITP), thrombocytopenia in adults with chronic liver disease (CLD), treatment of chemotherapy-induced thrombocytopenia (CIT), thrombotic thrombocytopenic purpura, acquired thrombocytopenia, etc.
About Mulpleta®
Mulpleta® (Lusutrombopag), which has already been approved for routine use in the United States, Europe Union and Japan, is an orally active, small molecule agonist of the human thrombopoietin (TPO) receptor that triggers the production of endogenous platelets. It is a new generation of TPO receptor agonist to benefit patients comprehensively by increasing platelets. With the characteristics of high response, safety and convenience, it can provide a well-tolerated and more effective treatment for patients with severe thrombocytopenia who require invasive surgery.
References:
1. Overview of the National Epidemic of Statutory Infectious Diseases in 2021 http://www.nhc.gov.cn/jkj/s3578/202204/4fd88a291d914abf8f7a91f6333567e1.shtml
2. Afdhal N, McHutchison J, Brown R, et al. Thrombocytopenia associated with chronic liver disease. J Hepatol. 2008;48(6):1000–7.
3. Bashour FN, Teran JC, Mullen KD. Prevalence of peripheral blood cytopenias (hypersplenism) in patients with nonalcoholic chronic liver disease. Am J Gastroenterol 2000; 95: 2936-2939 [PMID: 11051371 DOI:10.1111/j.1572-0241.2000.02325.x]
4. Information retrieval, A Frost & Sullivan Analysis.