Hypertension is a common cardiovascular disease. CCB (calcium channel antagonist), ACEI (angiotensin converting enzyme inhibitor), ARB (angiotensin receptor antagonist), diuretics, β -Blockers.
Amlodipine is a third-generation calcium channel antagonist. L-Amlodipine is a purified (S) -amlodipine for the treatment of hypertension, that is, amlodipine ((R)-and (S) -amlodipine Enantiomers with pharmacological activity in a racemic mixture). Mainly by blocking the calcium ion channels on vascular smooth muscle cells to expand blood vessels and reduce blood pressure, the mechanism of its antihypertensive effect is to directly relax vascular smooth muscles, thereby reducing blood pressure.
L-Amlodipine maleate was marketed in China under the name "Xuanning" as early as 2003, and accumulated a large amount of clinical data. L-Amlodipine Maleate “Intensive Blood Pressure Intervention Trial in Stroke Patients (IBIS)” and “China Acute Ischemic Stroke Antihypertensive Test II” two studies entered the national “Thirteenth Five-Year Plan” project, “Patients after stroke "Best Blood Pressure and Cholesterol Management Program Study (SHOT)", led by the European Hypertension Alliance + China Hypertension Alliance, will collect 2,500 cases in Europe and 5,000 cases in China.
2013-2017, National Leading Research Project of Leading New Drugs in the 12th Five-Year Plan, a LEADER study—Comparative effects of levamlodipine maleate and amlodipine besylate in the treatment of hypertension, Professor Huo Yong, Peking University First Hospital In the lead, the project has a sample size of more than 10,000 cases, covering 21 cities across the country, including 110 clinical research centers including Peking University First Hospital, Fuwai Cardiovascular Hospital of Chinese Academy of Medical Sciences, and Ruijin Hospital affiliated to Shanghai Jiaotong University. The core evaluation index of the LEADER study, the composite cardio-cerebrovascular event, was also evaluated by an independent endpoint event review committee.
The results show that half the dose of L-Amlodipine maleate is equivalent to that of amlodipine besylate, the blood pressure control rate of L-amlodipine maleate is 94.24%, and amlodipine besylate (import) 91.35%; The ability to prevent cardio-cerebral-vascular composite endpoint events in patients with hypertension is equivalent. The cumulative incidence of levamlodipine maleate combined with cardio-cerebral blood vessels is 4.57%, and amlodipine besylate (import) is 5.04%. In patients with hypertension of stroke and diabetes, L-Amlodipine maleate has a stronger tendency to prevent cardiovascular and cerebrovascular events; in terms of adverse reactions, L-Amlodipine maleate is significantly better than amlodipine besylate (import ), Especially in edema and headache, the performance is more prominent, the incidence of edema amlodipine maleate 1.1%, headache 0.7%, amlodipine besylate (import) edema incidence 2.8%, headache 1.1%. The development of the LEADER study and subsequent detailed data analysis have landmark significance in the history of hypertension drug research in China.
Xuanning launched the US clinic in 2014. In the United States, there is mutual recognition of clinical data on patents, but China's innovative clinical data is difficult to be recognized internationally, including FDA and some European countries certification. In 2017, China formally joined the ICH, the International Coordinating Technical Committee for the Registration of Human Drugs, to further improve the level and quality of drug development in China. Subsequently, the Food and Drug Administration of the State Food and Drug Administration issued a consultation draft on "Technical Requirements for Accepting Data from Overseas Clinical Trials", which accelerated the mutual recognition of clinical data at home and abroad, and provided tremendous support for the "in and out" of innovative drugs in China.
“The quality of our clinical data is very high and the information submitted is complete, so the FDA basically has no doubts.” It is worth mentioning that, as the first China approved, The FDA did not conduct a pre-approval inspection of CSPC's domestic production plant for the approved new drugs, which demonstrates its complete trust and affirmation of CSPC's quality control system, and also proves that China's pharmaceutical quality standards have fully reached the highest international standards.