JIXING Announces Completion of Patient Enrollment in China Cohort of Phase 3 Clinical Trial SEQUOIA-HCM of Aficamten
China data support global development program for a potential next-generation cardiac myosin inhibitor treatment for hypertrophic cardiomyopathy
SHANGHAI, China, June 5, 2023 –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 completion of patient enrollment in the China cohort of the Phase 3 clinical trial of aficamten (CK-3773274) for the potential treatment of symptomatic obstructive hypertrophic cardiomyopathy (oHCM). The China cohort is part of SEQUOIA-HCM, a global, multi-center pivotal Phase 3 clinical trial of aficamten.
“We are honored to participate in and successfully complete patient enrollment of the China cohort of the global SEQUOIA-HCM trial. During the enrollment process, we felt the urgent need for innovative oHCM therapies from physicians and patients.” 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, and Director of Cardiology Center of Beijing Anzhen Hospital of Capital Medical University. “We believe that aficamten, a cardiac myosin inhibitor, has the potential to significantly improve the current treatment standard and bring meaningful clinical benefits to oHCM patients.”
“We would like to thank all investigators and patients from 16 sites nationwide for their support. We are working closely with Cytokinetics to successfully execute the China cohort of SEQUOIA-HCM.” said Yuan Li, MD, Chief Medical Officer of Cardiovascular at JIXING. “We will also initiate more clinical studies for aficamten in China in the future, using China data to support the global development of aficamten as a potential next-generation cardiac myosin inhibitor treatment for hypertrophic cardiomyopathy.”
SEQUOIA-HCM is a global, multi-center, double-blind, randomized, placebo-controlled pivotal Phase 3 clinical trial designed to evaluate aficamten for 24 weeks in patients with symptomatic oHCM on standard of care treatment. 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, change in 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 approximately 270 patients globally, randomized on a 1:1 basis to receive aficamten or placebo in addition to standard-of-care treatment.
Aficamten is an investigational, selective, small-molecule cardiac myosin inhibitor with optimized therapeutic index and pharmacokinetic properties that may contribute to its best-in-class potential. 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 and stabilizing it in a weak actin-binding conformation. The development program for aficamten aims to assess its potential as a treatment for improving exercise capacity and relieving symptoms in patients with HCM as well as its potential long-term effects on cardiac structure and function. Aficamten has received a Breakthrough Therapy Designation for the treatment of symptomatic oHCM from the U.S. Food & Drug Administration (FDA) as well as the National Medical Products Administration (NMPA) in China.
Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disorder, and its prevalence is likely underestimated due to the current limitations of early screening. Globally, HCM is estimated to affect at least 1 in 200 people, with oHCM accounting for approximately 2/3 of cases and non-obstructive HCM for approximately 1/3 of cases in clinical practice. HCM may result in exertional dyspnea, fatigue, chest pain, syncope/presyncope and limited exercise capacity. It is a leading cause of death in young adults and athletes. HCM-related fatal and disabling events are most often attributable to sudden cardiac death, heart failure, and embolic stroke. Sudden cardiac death is the common cause of death in young HCM patients between 10 to 35 years old, while heart failure and stroke due to HCM-related atrial fillbrillation represent the common cause of death in middle-aged and elderly patients, respectively. The annual mortality rate for HCM patients in hospitals is 2% to 4%.
At present, there are no disease-specific drugs approved for HCM in China. Patients with symptomatic oHCM are generally offered pharmacotherapy with non-HCM-specific agents such as 𝛽-blockers, verapamil, diltiazem and disopyramide based on clinicians’ experience; however, these medications do not target the underlying pathology (i.e., hypercontractility) and provide only symptomatic relief with variable effectiveness and risks of significant adverse effects. 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 requires an expertise that is not widely accessible in China and carry risks of complications including death.
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.jixing.com.
- The Joint Committee of Cardiomyopathy Specialty Alliance, National Center for Cardiovascular Diseases/Cardiovascular Precision Medicine Branch of China International Exchange and Promotive Association for Medical and Health Care. 2023 Guideline for Diagnosis and Treatment of Patients With Hypertrophic Cardiomyopathy. Chinese Circulation Journal, 2023, 38: 1.
- Chinese Heart Failure Association of Chinese Medical Doctor Association, National Heart Failure
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- Cytokinetics website.