JIXING Announces the First Patient Enrolled in China Cohort of Phase 3 Clinical Trial of Aficamten
China cohort is part of the global multi-center Phase 3 clinical trial, SEQUOIA-HCM, investigating a next-in-class potential treatment for hypertrophic cardiomyopathy
SHANGHAI, China, August 26, 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, announces the first patient enrolled at Beijing Anzhen Hospital of Capital Medical University in its conduct of the China cohort of the Phase 3 clinical trial of aficamten for the treatment of symptomatic obstructive hypertrophic cardiomyopathy (oHCM). The China cohort of the trial is currently being carried out in 16 clinical centers across China. The trial is designed to evaluate the efficacy and safety of aficamten as a potential treatment for oHCM and to provide clinical data to support a new drug application in China. This China trial is part of SEQUOIA-HCM, an international, multi-center Phase 3 clinical trial of aficamten, being conducted outside China by Cytokinetics, Incorporated (Cytokinetics).
Aficamten, discovered by Cytokinetics, is a next-in-class cardiac myosin inhibitor in development for the potential treatment of hypertrophic cardiomyopathy (HCM). 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 HCM. Aficamten has already 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 oHCM.
“HCM is a common inherited cardiovascular disorder. The current treatment of patients with oHCM is based on clinical experience but does not target the underlying pathology which is hypercontractility, ” said Professor Changsheng Ma, Principal Investigator of the China cohort of the Phase 3 clinical trial, Chairman-designate of the Cardiovascular Branch of the Chinese Medical Association, Director of National Clinical Research Center for Cardiovascular Diseases, Director of Cardiology Center of Beijing Anzhen Hospital of Capital Medical University. “We believe that aficamten, as a cardiac myosin inhibitor, has the potential to significantly improve the current treatment status and have a meaningful clinical impact for patients. As part of the global multi-center trial, the data of China cohort will also support the innovative development of aficamten.”
“There are no approved disease-specific drugs for oHCM in China targeting the underlying pathophysiological mechanisms. We are conducting the China cohort of the global Phase 3 clinical trial, SEQUOIA-HCM, under our collaboration agreement with Cytokinetics and hope to bring this potential new medicine aficamten to Chinese patients soon,” said Yuan Li, MD, Chief Medical Officer of Cardiovascular at JIXING. “China has the largest cardiovascular disease patient population and huge unmet medical needs. We have already established a solid cardiovascular pipeline of 3 assets in late-stage clinical development targeting 6 indications. We are committed to working closely with the medical community to have innovative therapies benefit Chinese patients.”
SEQUOIA-HCM builds on the positive results from REDWOOD-HCM, a Phase 2 clinical trial of aficamten conducted by Cytokinetics, that demonstrated that treatment with aficamten for 10 weeks resulted in reductions from baseline compared to placebo in the average resting left ventricular outflow tract pressure gradient (LVOT-G) and the average post-Valsalva LVOT-G, with no treatment interruptions or discontinuations, nor any treatment-related serious adverse events.
Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disorder. The prevalence is 80/100000 and it is estimated that there are more than 1 million HCM adult patients in China. HCM may result in exertional dyspnea, fatigue, chest pain, syncope/presyncope and limited exercise capacity. HCM is one of the main reasons of death in teenagers and athletes. Disease-related mortality is most often attributable to sudden cardiac death, heart failure, and embolic stroke. 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 hospitals 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, 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.
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.
SEQUOIA-HCM is a Phase 3 randomized, placebo-controlled, double-blind, international multi-center clinical trial designed to evaluate aficamten in patients with symptomatic obstructive HCM on background medical therapy for 24 weeks. The primary endpoint is the change in peak oxygen uptake (pVO2) measured by cardiopulmonary exercise testing (CPET) from baseline to Week 24. Secondary endpoints include the change from baseline to Week 12 and Week 24 in Kansas City Cardiomyopathy Questionnaire (KCCQ) score, proportion of patients with ≥1 class improvement in New York Heart Association (NYHA) functional class, post-Valsalva left ventricular outflow tract gradient (LVOT-G), and proportion of patients with post-Valsalva LVOT-G <30 mmHg, as well as the change from baseline to Week 24 in total workload during CPET. SEQUOIA-HCM is expected to enroll 270 patients, including Chinese patients, randomized on a 1:1 basis to receive aficamten or placebo in addition to standard-of-care treatment.
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. For additional information about JIXING, visit www.jixingbio.com.
Cytokinetics is a late-stage biopharmaceutical company focused on discovering, developing and commercializing first-in-class muscle activators and next-in-class muscle inhibitors as potential treatments for debilitating diseases in which muscle performance is compromised. As a leader in muscle biology and the mechanics of muscle performance, the company is developing small molecule drug candidates specifically engineered to impact muscle function and contractility. Cytokinetics is readying for the potential commercialization of omecamtiv mecarbil, its cardiac muscle activator, following positive results from GALACTIC-HF, a large, international Phase 3 clinical trial in patients with heart failure. Cytokinetics is also developing aficamten, a next-generation cardiac myosin inhibitor, currently the subject of SEQUOIA-HCM, the Phase 3 clinical trial of aficamten in patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM). Aficamten is also being evaluated in non-obstructive HCM in Cohort 4 of the Phase 2 clinical trial, REDWOOD-HCM. Cytokinetics is also developing reldesemtiv, an investigational fast skeletal muscle troponin activator, currently the subject of COURAGE-ALS, a Phase 3 clinical trial in patients with amyotrophic lateral sclerosis (ALS). Cytokinetics continues its over 20-year history of pioneering innovation in muscle biology and related pharmacology focused to diseases of muscle dysfunction and conditions of muscle weakness. For additional information about Cytokinetics, visit www.cytokinetics.com.
- 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.
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- Cytokinetics website.