JIXING Announces Receipt of Clinical Trial Application Approval for China Cohort of Phase 3 Clinical Trial of Aficamten
Aficamten has already been granted Breakthrough Therapy Designation for the treatment of symptomatic obstructive hypertrophic cardiomyopathy (oHCM) in China and US
SHANGHAI, China, June 29, 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 that the Center for Drug Evaluation (CDE) of the National Medical Products Administration of the PRC (NMPA) has approved the Clinical Trial Application (CTA) for the China cohort of the Phase 3 clinical trial of aficamten (CK-3773274) for the treatment of symptomatic obstructive hypertrophic cardiomyopathy (oHCM), which is part of SEQUOIA-HCM, an international, multi-center Phase 3 clinical trial of aficamten.
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 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 symptomatic obstructive hypertrophic cardiomyopathy (oHCM).
“There are no approved disease-specific drugs for oHCM in China targeting the underlying pathophysiological mechanisms. We believe that aficamten has the potential to significantly improve the current treatment status and have a meaningful impact for patients,” said Yuan Li, MD, Chief Medical Officer of Cardiovascular at JIXING. “We look forward to conducting the China cohort of the global Phase 3 clinical trial, SEQUOIA-HCM, under our collaboration agreement with Cytokinetics and bringing this potential new medicine to Chinese patients soon.”
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. SEQUOIA-HCM is expected to enroll 270 patients, including Chinese patients.
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. 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.
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 Greater China.
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, 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.
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.
- 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.
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- Cytokinetics website.