JIXING Announces Positive Results From The China Cohort Of SEQUOIA-HCM, The Pivotal Phase 3 Clinical Trial Of Aficamten In Patients With Obstructive Hypertrophic Cardiomyopathy
Aficamten Meets Primary Endpoint in Study of Patients with Obstructive Hypertrophic Cardiomyopathy
China Cohort Results Show Consistency With Overall Population in Efficacy and Safety
SHANGHAI, China, December 30, 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, today announced that in the SEQUOIA-HCM, the pivotal phase 3 clinical trial of aficamten, the China cohort that received treatment with aficamten for 24 weeks, significantly improved exercise capacity compared to placebo, increasing peak oxygen uptake (pVO2) measured by cardiopulmonary exercise testing (CPET) by a least square mean difference (95% CI) of 2.38 (0.39 - 4.36) mL/kg/min (nominal p <0.05), consistent with the results of the overall phase 3 clinical trial population (a least square mean difference (95% CI) of 1.74 (1.04 - 2.44) mL/kg/min (p=0.000002)).
The China cohort results were consistent with overall population efficacy for all other prespecified secondary endpoints, including Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS) at weeks 12 and 24, the proportion of patients with ≥1 class improvement in New York Heart Association (NYHA) functional class at weeks 12 and 24, change in provoked left ventricular outflow tract gradient (LVOT-G) and proportion <30 mmHg at weeks 12 and 24, as well as exercise workload.
Aficamten was well-tolerated in the China cohort of SEQUOIA-HCM with an adverse event profile comparable to placebo. Treatment emergent serious adverse events occurred in 0 and 2 (9.1%) patients on aficamten and placebo, respectively. Core echocardiographic left ventricular ejection fraction (LVEF) was observed to be <50% in 1 patient (4.2%) on aficamten compared to 0 patients on placebo. There were no instances of worsening heart failure or treatment interruptions due to low LVEF in China cohort.
"Analysis of the overall population data from the SEQUOIA-HCM study showed statistically significant and clinically meaningful improvements in the primary efficacy endpoint as well as all secondary endpoints at 24 Weeks of treatment. I am pleased to see that the efficacy results in the China cohort were consistent with the overall population, and that aficamten was well tolerated in the Chinese population, which may reflect a profile that will enable aficamten to become the cardiac myosin inhibitor of choice among 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. "As a cardiac myosin inhibitor, Aficamten has the potential to transform oHCM treatment and is expected to provide significant clinical benefits to Chinese oHCM patients. "
“We would like to thank all investigators and patients from 16 sites nationwide for their support. And we will communicate with the drug regulatory authorities for aficamten’s new drug application as soon as possible in order to benefit Chinese oHCM patients," said Sandy Mou, Board Executive Director and Chief Executive Officer of JIXING.
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.
Additional information
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 potential long-term effects on cardiac structure and function. Aficamten was evaluated in SEQUOIA-HCM (Safety, Efficacy, and Quantitative Understanding of Obstruction Impact of Aficamten in HCM), a pivotal Phase 3 clinical trial in patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM). Aficamten is currently the subject of two ongoing Phase 3 clinical trials: MAPLE-HCM (Metoprolol vs Aficamten in Patients with LVOT Obstruction on Exercise Capacity in HCM), evaluating aficamten as monotherapy compared to metoprolol as monotherapy in patients with obstructive HCM, and ACACIA-HCM (Assessment Comparing Aficamten to Placebo on Cardiac Endpoints In Adults with Non-Obstructive HCM), evaluating aficamten in patients with symptomatic non-obstructive HCM. Aficamten received Breakthrough Therapy Designation for the treatment of symptomatic obstructive HCM from the U.S. Food & Drug Administration (FDA) as well as the National Medical Products Administration (NMPA) in China.
Hypertrophic cardiomyopathy (HCM) is a disease in which the heart muscle (myocardium) becomes abnormally thick (hypertrophied). The thickening of cardiac muscle leads to the inside of the left ventricle becoming smaller and stiffer, and thus the ventricle becomes less able to relax and fill with blood. This ultimately limits the heart’s pumping function, resulting in reduced exercise capacity and symptoms including chest pain, dizziness, shortness of breath, or fainting during physical activity. HCM is the most common monogenic inherited cardiovascular disorder, with approximately 280,000 patients diagnosed in the U.S., however, there are an estimated 400,000-800,000 additional patients who remain undiagnosed.1,2,3 Two-thirds of patients with HCM have obstructive HCM (oHCM), where the thickening of the cardiac muscle leads to left ventricular outflow tract (LVOT) obstruction, while one-third have non-obstructive HCM (nHCM), where blood flow isn’t impacted, but the heart muscle is still thickened. People with HCM are at high risk of also developing cardiovascular complications including atrial fibrillation, stroke and mitral valve disease.4 People with HCM are at risk for potentially fatal ventricular arrhythmias and it is one of the leading causes of sudden cardiac death in younger people or athletes.5 A subset of patients with HCM are at high risk of progressive disease leading to dilated cardiomyopathy and heart failure necessitating cardiac transplantation.
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.
JIXING’s cardiovascular portfolio includes 3 assets in late-stage clinical development (aficamten, etripamil, omecamtiv mecarbil) and 1 in pre-clinical stage (JX09). JIXING’s ophthalmology portfolio includes 4 assets in late-stage clinical development (varenicline solution nasal spray/US brand name TYRVAYA, OC-02 nasal spray, JX06/LNZ100, JX07/LNZ101) and 1 asset in pre-clinical stage (JX08). For further information about JIXING, please visit www.jixing.com .
Contacts:
References:
1. CVrg: Heart Failure 2020-2029, p 44; Maron et al. 2013 DOI: 10.1016/S0140-6736(12)60397-3; Maron et al 2018 10.1056/NEJMra1710575
2. Symphony Health 2016-2021 Patient Claims Data DoF;
3. Maron MS, Hellawell JL, Lucove JC, Farzaneh-Far R, Olivotto I. Occurrence of Clinically Diagnosed Hypertrophic Cardiomyopathy in the United States. Am J Cardiol. 2016; 15;117(10):1651-1654.
4. Gersh, B.J., Maron, B.J., Bonow, R.O., Dearani, J.A., Fifer, M.A., Link, M.S., et al. 2011 ACCF/AHA guidelines for the diagnosis and treatment of hypertrophic cardiomyopathy. A report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Journal of the American College of Cardiology and Circulation, 58, e212-260.
5. Hong Y, Su WW, Li X. Risk factors of sudden cardiac death in hypertrophic cardiomyopathy. Current Opinion in Cardiology. 2022 Jan 1;37(1):15-21
