JIXING Announces NMPA Acceptance of New Drug Application Submission for Omecamtiv Mecarbil
The first in class selective, small molecule cardiac myosin activator has the potential to be an additional treatment option for patients with heart failure with reduced ejection fraction
Shanghai, China, November 7, 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 the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) of the PRC has accepted the submission of the New Drug Application (NDA) for omecamtiv mecarbil for the treatment of heart failure with reduced ejection fraction (HFrEF) in China.
Omecamtiv mecarbil, discovered and developed by Cytokinetics, Incorporated (Cytokinetics) is an investigational, selective, small molecule cardiac myosin activator, the first of a novel class of myotropes designed to directly target the contractile mechanisms of the heart, binding to and recruiting more cardiac myosin heads to interact with actin during systole. In February 2022, Cytokinetics announced U.S. Food & Drug Administration (FDA) acceptance of the NDA submission for omecamtiv mecarbil. JIXING has an exclusive license to develop and commercialize omecamtiv mecarbil for the treatment of HFrEF in Greater China pursuant to a License and Collaboration Agreement with Cytokinetics.
“This is our first NDA submission for a Class I New Drug accepted for review by China NMPA. We look forward to engaging with the NMPA and medical community to bring this potential first-in-class new drug to Chinese HFrEF patients soon,” said Dr Peter Fong, Board Executive Director and CEO of JIXING. “This is an important milestone for JIXING’s business growth to become an innovative biotech company with both development and commercialization capabilities to bridge the innovation gap for patients in China and the world.”
The prevalence of chronic heart failure has been rising in China, affecting more than 12 million patients, of which, HFrEF accounts for as much as 40%. A large number of HFrEF patients have signs and symptoms of worsening heart failure despite standard of care therapy. The 5-year survival rate for patients with heart failure is only 60%.
“Omecamtiv mecarbil may bring an additional option for the treatment of HFrEF in China. China has the largest cardiovascular disease patient population and JIXING has been committed from the start to addressing cardiovascular diseases as the leading cause of death,” said Kun Wu, Chief Commercial Officer of JIXING. “We have established a solid cardiovascular pipeline of 3 assets in late-stage clinical development targeting 6 indications. The NDA submission for omecamtiv mecarbil will greatly help advance our progress towards product commercialization with the goal of benefitting more patients. “
The NDA is supported by the results from GALACTIC-HF (Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure), the Phase 3 cardiovascular outcomes clinical trial of omecamtiv mecarbil that enrolled over 8,000 patients in 35 countries across 945 sites and the results of subgroup analysis of China subjects. A total of 400 Chinese patients were enrolled and randomized in GALACTIC-HF at 41 study centers in China. Subgroup analyses from GALACTIC-HF demonstrated a statistically significant effect of treatment with omecamtiv mecarbil to reduce risk of the primary composite endpoint of cardiovascular (CV) death or heart failure events (heart failure hospitalization and other urgent treatment for heart failure) compared to placebo in Chinese patients treated with standard of care. This result was consistent with those observed in the overall study population and showed a trend toward greater benefit with omecamtiv mecarbil in the China subgroup.
Additional information
Omecamtiv mecarbil is an investigational, selective, small molecule cardiac myosin activator, the first of a novel class of myotropes1 designed to directly target the contractile mechanisms of the heart, binding to and recruiting more cardiac myosin heads to interact with actin during systole. Omecamtiv mecarbil is designed to increase the number of active actin-myosin cross bridges during each cardiac cycle and consequently augment the impaired contractility that is associated with heart failure with reduced ejection fraction (HFrEF). Preclinical research has shown that omecamtiv mecarbil increases cardiac contractility without increasing intracellular myocyte calcium concentrations or myocardial oxygen consumption.2-4
The development program for omecamtiv mecarbil is assessing its potential for the treatment of HFrEF. Positive results from GALACTIC-HF, the first Phase 3 clinical trial of omecamtiv mecarbil demonstrated a statistically significant effect of treatment with omecamtiv mecarbil to reduce risk of the primary composite endpoint of cardiovascular (CV) death or heart failure events (heart failure hospitalization and other urgent treatment for heart failure) compared to placebo in patients treated with standard of care. No reduction in the secondary endpoint of time to CV death was observed. Adverse events and treatment discontinuation of study drug were balanced between treatment arms. The FDA has accepted for filing the NDA for omecamtiv mecarbil based on the results from GALACTIC-HF and has assigned a Prescription Drug User Fee Act (PDUFA) date of February 28, 2023.
Heart failure (HF) is a complex clinical syndrome caused by changes in cardiac structure and/or function, resulting in ventricular systolic and/or diastolic dysfunction. It is mainly manifested as dyspnea, fatigue, and fluid retention (pulmonary congestion, systemic congestion and peripheral edema). It is also a serious manifestation or advanced stage of various heart diseases5. HF affects approximately 64 million people worldwide 6. In China, the prevalence of HF among population ≥25 years old was 1.10%, which meant that the estimated total number of individuals ≥25 years old with HF in China was more than 12 million and the prevalence increases with age7.
According to the left ventricular ejection fraction (LVEF), HF is classified as HF with reduced LVEF (HFrEF, LVEF≤40%), HF with improved LVEF (HFimpEF, previous LVEF≤40% and a follow-up measurement of LVEF>40%), HF with mildly reduced LVEF (HFmrEF, LVEF 41%- 49%), and HF with preserved LVEF (HFpEF, LVEF≥50%)8. In a Chinese cohort, the 5-year mortality rate in HFrEF patients is significantly higher than in other types9.
Although remarkable achievements have been made in the prevention and treatment of HF, the overall prognosis of HF is still poor. Data showed that the 30-day and 1-year readmission rates of patients with HF after discharge in China are 19% and 53%, while the mortality rates are 14% and 29%, respectively10. Given the number of patients with HF, repeated hospitalizations and death place a significant burden on both families and the health care system.
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.
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.
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References:
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