JIXING Presents Results of China Phase I Study of Aficamten at the 2022 American Society for Clinical Pharmacology and Therapeutics Annual Meeting
Aficamten shown to be safe and well tolerated in first study in healthy Chinese adults
SHANGHAI, China, March 17, 2022 – Ji Xing Pharmaceuticals Limited (JIXING), a clinical-stage biopharmaceutical company committed to bringing innovative medicines to underserved Chinese patients with serious and life-threatening diseases, today announced that results of the China Phase 1 study of aficamten were presented as an e-poster at the 2022 American Society for Clinical Pharmacology and Therapeutics (ASCPT) Annual Meeting.
Aficamten, discovered by Cytokinetics, Incorporated (Cytokinetics), is a next-generation cardiac myosin inhibitor in development for the potential treatment of hypertrophic cardiomyopathy (HCM). Aficamten has received Breakthrough Therapy Designation from the U.S. Food and Drug Administration (FDA) and the National Medical Products Administration (NMPA) of the PRC for the treatment of symptomatic obstructive hypertrophic cardiomyopathy (oHCM).
The study (JX01001; NCT04783766) is the first completed clinical study of an investigational cardiac myosin inhibitor in healthy Chinese subjects. The major objective of the study was to evaluate the safety, tolerability, and pharmacokinetics of aficamten in healthy Chinese subjects. A total of 28 subjects were randomized and completed the study. Overall, the results showed a safety and tolerability profile comparable to placebo and dose-proportional pharmacokinetics, similar to the results observed in the Phase 1 study of aficamten in healthy, mostly Caucasian subjects in the US.
Aficamten is an investigational selective, small molecule cardiac myosin inhibitor discovered following an extensive chemical optimization program that was conducted with careful attention to therapeutic index and pharmacokinetic properties and as may translate into next-in-class potential in clinical development. Aficamten was designed to reduce the number of active actin-myosin cross bridges during each cardiac cycle and consequently suppress the myocardial hypercontractility that is associated with hypertrophic cardiomyopathy (HCM). In preclinical models, aficamten reduced myocardial contractility by binding directly to cardiac myosin at a distinct and selective allosteric binding site, thereby preventing myosin from entering a force producing state. The development program for aficamten is assessing its potential as a treatment that improves exercise capacity and relieves symptoms in patients with HCM as well as its long-term effects on cardiac structure and function.
In July 2020, JIXING entered into a license and collaboration agreement with Cytokinetics, a late-stage biopharmaceutical company headquartered in California, pursuant to which Cytokinetics has granted to JIXING an exclusive license to develop and commercialize aficamten (formerly known as CK-274) in the Greater China territory.
Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disorder. The prevalence is 80/100000 in China and it is estimated that there are more than 1.5 million HCM patients in China. HCM may result in exertional dyspnea, fatigue, chest pain, syncope/presyncope and limited exercise capacity. Disease-related mortality is most often attributable to sudden cardiac death, heart failure, and embolic stroke. HCM is one of the main reasons of death in teenagers and athletes. Sudden cardiac death is the common mode of death in young patients between 10 to 35 years old. Heart failure is the common mode of death in middle-age patients and stroke due to HCM related atrial fibrillation is common in old patients. The annual mortality rate for HCM patients in tertiary care centers is 2% to 4%.
At present, there are no approved drugs that are disease-specific for HCM in China. Patients with symptomatic obstructive hypertrophic cardiomyopathy (oHCM) are generally offered pharmacotherapy with 𝛽-blockers, verapamil, diltiazem and disopyramide based on experience; however, these medications often do not prevent progression of the disease, are associated with significant adverse effects, are originally intended to treat other conditions, and do not target the underlying pathology (hypercontractility). Additionally, disopyramide is not available in China. For oHCM patients with a left ventricular outflow tract pressure gradient (LVOT-G) of ≥50 mm Hg either at rest or with provocation who also have severe symptoms refractory to medical therapy, septal reduction therapies (such as surgical myectomy or percutaneous alcohol septal ablation) can be effective, but these invasive procedures are not widely accessible in China and carry risk including death. Septal reduction therapies and their success depends on operator experience. These available treatments do not address the underlying pathology of HCM (hypercontractility) either.
The American Society for Clinical Pharmacology and Therapeutics (ASCPT) was founded in 1900, and consists of over 2,300 professionals whose primary interest is to advance the science and practice of clinical pharmacology and translational science for the therapeutic benefit of patients and society. ASCPT is the largest scientific and professional organization serving the disciplines of clinical pharmacology and translational science.
ASCPT focuses on improving the understanding and use of existing drug therapies and developing safer and more effective treatments for the future. ASCPT memberships' unique combination of scientific and clinical expertise makes them especially qualified to understand the impact of disease on patients, the compelling need for effective drug therapy, and the efforts necessary to meet those needs. Such efforts include research, exchange of scientific information, and awareness of legislative requirements that affect drug development and regulation.
JIXING is a biopharmaceutical company headquartered in Shanghai committed to bringing innovative science and medicines to underserved patients in China with serious and life-threatening diseases. Backed by RTW Investments, LP, JIXING was founded in 2019 and partners with global biotechnology companies to develop and commercialize novel, innovative therapeutics to treat unmet medical needs in cardiovascular and ophthalmic diseases. With a strong and further developing asset pipeline, seasoned management team, and patient-centric focus, JIXING is dedicated to delivering a meaningful and lasting impact on patients in Greater China.
- Heart failure committee of Chinese medical association, Editorial board of the Chinese journal of heart failure and cardiomyopathy. 2017 Guidelines of hypertrophic cardiomyopathy management in China. Chin J Heart Fail & Cardiomyopathy. 2017; 1(2): 65-86.
- Guideline writing group for the diagnosis and treatment of adult hypertrophic cardiomyopathy in Chinese cardiology society of Chinese medical association, Editorial board of Chinese journal of cardiovascular diseases. 2017 Guideline for the diagnosis and treatment of adult hypertrophic cardiomyopathy. Chin J Cardiol. 2017;45(12): 1015-1031.
- Ommen SR et al. 2020 AHA/ACC Guideline for the Diagnosis and Treatment of Patients With Hypertrophic Cardiomyopathy. Circulation. 2020 Dec 22;142(25): e533-e557.
- Cytokinetics website.
- ASCPT website.