Edding announced that the Phase III clinical trial in mainland China was successfully completed and achieved the positive, statistically significant top-line results from Study No. 1903M0636today.
The 1903M0636 trial was a multi-center, randomized, double-blind, placebo-controlled phase III clinical study to assess the efficacy and safety of Lusutrombopag (S-888711) for the treatment of Thrombocytopenia in chronic liver disease (CLD) patients who are scheduled to undergo elective invasive procedures in Chinese population.
The results showed that, in the preoperative platelet-raising treatment of patients with thrombocytopenia in CLD who were candidates for elective invasive surgery, the proportion of responders on Day 8 was significantly higher in the Lusutrombopag group compared to the placebo group at the primary endpoint. And the key secondary endpoint of the Lusutrombopag group was statistically significant too compared to the placebo group, and other secondary endpoints also supported the clinical therapeutic effect of Lusutrombopag.
With regard to safety, Lusutrombopag showed good safety and tolerability. Compared with the placebo group, the Lusutrombopag group had a similar incidence of adverse events, and no serious adverse events related to the study drug occurred. The results of this study are consistent with the results of the previous Phase III studies (L-PLUS 1 and L-PLUS 2) conducted overseas for Lusutrombopag.
The results of this trial will be used to support Edding’s dossier for seeking regulatory approval of Mulpleta® (Lusutrombopag) in Mainland China.
According to the latest data from the World Health Organization (WHO), there are currently nearly 100 million hepatitis B patients, and more than 400 million patients with various liver diseases in China. Altered liver function can reduce the production and/or activity of the hematopoietic growth factor thrombopoietin (TPO), leading to thrombocytopenia, which can cause problems for patients with liver disease who require selective invasive surgery.
The Frost & Sullivan report shows that the number of patients with thrombocytopenia associated with chronic liver disease will increase to 7.3 million by 2030, with a huge clinical need and a market size of RMB 8.5 billion. Currently, most patients with thrombocytopenia caused by chronic liver disease are treated by platelet transfusion in clinical practice. However, the platelet resources in China are limited and there is a large gap between the clinical needs, so the clinical application of thrombopoietinreceptor agonist (TPO-RA) drugs is significant.
Lusutrombopag is the latest generation of oral small-molecule TPO receptor agonists. Compared with the first generation, it is safer, convenient to use, and non-immunogenic and stable efficacy, providing patients with better medical options. By acting on the transmembrane domain of the human TPO receptors, Lusutrombopag activates the signal transduction pathway in the same manner as endogenous TPO to promote the production of platelets.
Mulpleta® has been approved for marketing in the Japan (2015.9), the U.S. (2018.8) and the EU (2019.2), which is indicated for the treatment of thrombocytopenia (TCP) in adult patients with chronic liver disease (CLD) who are scheduled to undergo elective invasive surgery or diagnostic manipulation.
In 2019, Edding announced an agreement with Shionogi Pharmaceutical Co., Ltd., Japan, in-licensed lusutrombopag, a TPO-RA (brand name in Japan: Mulpleta®）for development and commercialization in mainland China, Hong Kong(China) and Macau(China).
The Leading principal investigator (PI) of the trial，Prof. Zhou Jian ( Vice president of Zhongshan Hospital Fudan University，Director of Liver Surgery Department) said，we are very pleased that the Phase III clinical trial of lusutrombopag was successfully completed with positive results in Mainland Chinathanks to the united collaboration of the project team and all parties . Lusutrombopag is a small-molecule TPO-RA, and its efficacy and safety have reached expectations, providing patients with more options for later clinical surgery.
“About 20,000 patients were screened in the Phase III clinical trial of Lusutrombopag, and 66 patients were randomly enrolled.” said James He, the Chief Medical Officer of Edding Pharma. Although the trial development process also encountered the COVID-19, our team overcame various difficulties and adhered to a scientific and rigorous attitude to promote the progress of clinical trials. He also said，“We are pleased to see that Lusutrombopag has finally achieved positive results in the Phase III clinical trial. We will continue working with all collaborators to bring this cross-era innovative drug into China and benefit Chinese patients.”
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 2020 ranked first (1,138,781), and the incidence ranked first, about 81/ 100,000[1].
Chronic liver disease (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. According to reports, up to about 70% of patients have varying degrees of thrombocytopenia, and about 14% are complicated with severe thrombocytopenia[2].
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[3].
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), adult patients with chronic liver disease Thrombocytopenia (CLD), treatment of chemotherapy-induced thrombocytopenia (CIT), thrombotic thrombocytopenic purpura, acquired thrombocytopenia, etc.