Recently, the last subject was successfully enrolled in Phase II clinical trial of PUK (recombinant human pro-urokinase for injection) thrombolysis for the treatment of acute pulmonary embolism, the national first-class biological new drug independently innovated by Tasly Biopharmaceuticals Co., Ltd. (hereinafter referred to as “Tasly Biopharma”).
Acute Pulmonary Embolism Phase II Clinical Trial
The investigational drug PUK (recombinant human pro-urokinase for injection), a thrombolytic drug for the treatment of acute ST-Segment Elevation Myocardial Infarction, is the only commercialized recombinant human pro-urokinase product in China. Approved for new drug application in 2011, PUK is the first Class I biologic drug approved by National Medical Products Administration to have received funding under the National Science and Technology Major Project — Major Innovative Drug Development. In 2017, PUK was included into the “Catalog of Medicines” covered by National Medical Insurance System. As the new generation of fibrin-specific thrombolytic drugs, PUK has stronger specificity for thrombolysis and embolization thrombus compared with other thrombolytic drugs, and does not form the complex with proteolytic enzyme inhibitors. The clinical recanalization rate for acute myocardial infarction after thrombolysis is 85%, and the incidence of intracranial hemorrhage is only 0.29%.
Acute pulmonary embolism (APE) is the most serious clinical manifestation of venous thromboembolism (VTE), and is the main cause of adverse clinical events such as death and hospitalization. Hemodynamics and respiratory support, anticoagulation, thrombolysis, surgical thrombectomy, percutaneous catheter intervention, venous filter, etc. are the treatment measures for acute pulmonary embolism, among which thrombolysis and anticoagulation therapy have been widely adopted by domestic and foreign experts.
Tasly Biopharma’s Recombinant Human Pro-urokinase for Injection Thrombolysis of Acute Pulmonary Embolism (APE) Phase III clinical trial, led by Fuwai Hospital Chinese Academy of Medical Sciences, with Professor Jing Zhicheng as the prinpical investigator, uses alteplase for injection (rt-PA) as a control, and preliminary evaluates the efficacy and safety of recombinant human pro-urokinase for injection (pro-UK) in the treatment of acute pulmonary embolism (APE). At present, all 108 subjects have been enrolled. This study is a large-scale clinical study on thrombolysis for the treatment of acute pulmonary infarction in China. The approval of the product will benefit the majority of patients with acute pulmonary infarction.
APE Clinical Development Progress
The target patients of this study are high-risk and medium-high-risk with acute disease. The successful rate of informed consent of high-risk patients during the study is extremely low. At the same time, the study protocol has strict requirements for the selection of middle and high-risk patients, and the screening rate is less than 10%, which is difficult for enrollment. The first patient of the Acute Pulmonary Embolism (APE) Phase II clinical trial was enrolled in March 2017. During this period, the project team actively promoted the clinical trial and screening with the support of investigators from all trial centers across the country. As of November 18, 2019, the last patient was successfully enrolled.
APE Future Market Prospects
For APE patients, thrombolysis is one of the mainstream treatment measures at present. Thrombolysis can quickly dissolve thrombus, clear blood vessels, restore lung tissue perfusion, reverse the right heart failure, increase pulmonary capillary blood volume and reduce fatality rate and recurrence rate. According to Frost & Sullivan data, there were approximately 218,600 APE patients in China in 2018, and it is estimated that this number will reach approximately 282,400 in 2023. According to the “Chinese Expert Consensus on the Diagnosis and Treatment of Acute Pulmonary Embolism”, thrombolysis is recommended for APE patients in the high-risk group and the middle-high-risk group.
At present, APE patients have fewer options for thrombolytic products. The development of this indication has a far-reaching impact on the further exploration of PUK terminal market.