CORXEL Announces NMPA Acceptance of Priority Review for Aficamten
SHANGHAI, China, December 4， 2024 – Corxel Pharmaceuticals (CORXEL), formerly named Ji Xing Pharmaceuticals, a leading biotech company committed to bringing innovative science and medicines to underserved patients with serious and life-threatening cardiometabolic diseases，today announced that the Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) of the PRC has designated the NDA for Aficamten tablets for the treatment of symptomatic obstructive hypertrophic cardiomyopathy (oHCM) for priority review.
This priority review is based on the submission of positive results from SEQUOIA-HCM, the global pivotal Phase 3 clinical trial of aficamten in patients with obstructive hypertrophic cardiomyopathy. SEQUOIA-HCM enrolled 282 patients with obstructive HCM. The results of SEQUOIA-HCM showed that treatment with aficamten significantly improved exercise capacity compared to placebo, The treatment effect with aficamten was consistent across all prespecified subgroups reflective of patient baseline characteristics and treatment strategies, including patients receiving or not receiving background beta-blocker therapy and those enrolled in China. Statistically significant and clinically meaningful improvements were also observed in all 10 prespecified secondary endpoints. Aficamten was well-tolerated in SEQUOIA-HCM with an adverse event profile comparable to placebo. Treatment emergent serious adverse events occurred in 5.6% and 9.3% of patients on aficamten and placebo, respectively.
In 2022, CDE granted Breakthrough Therapy Designation for aficamten for the treatment of symptomatic oHCM in China.
“As the next-in-class cardiac myosin inhibitor (CMI), aficamten's acceptance for priority review demonstrates the unmet clinical need and further highlights its potential to become a “best-in-class” treatment in the field of oHCM therapy.” Sandy Mou, Board Executive Director and Chief Executive Officer of CORXEL, said: "We’ll accelerate aficamten’s approval in China via the priority review, thus providing more treatment options for Chinese oHCM patients. This will guarantee that patients can benefit from this cutting-edge therapy as soon as possible, in addition to helping to establish aficamten as the preferred cardiac myosin inhibitor for both physicians and patients.”
Additional information
Aficamten is an investigational selective, small molecule cardiac myosin inhibitor from Cytokinetics, Incorporated (Nasdaq: CYTK), 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.
Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disorder, and the prevalence is likely to be underestimated due to the limitations of early screening. The prevalence is currently estimated to be at least 1/200, with obstructive (either at rest or with provocation) HCM 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. HCM is one of the main reasons of death in teenagers and athletes. Disease-related fatal and disabling events are 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-aged 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, 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.
CORXEL, formerly named Ji Xing Pharmaceuticals, is a leading biotech company headquartered in US and China focused on developing innovative cardiometabolic therapies globally. Backed by RTW Investments, LP, CORXEL was founded in 2019 and has been committed to bringing innovative science and medicines to underserved patients around the world. With a strong and further developing asset pipeline, industry leading talent, and patient-centric focus, CORXEL is dedicated to deliver a meaningful and lasting impact on patients.
The full portfolio of CORXEL consists of 2 assets with global rights and 4 assets with Greater China rights in late-stage clinical development. The portfolio with global rights are JX09 for hypertension and JX10 for acute ischemic stroke (AIS), while the portfolio with Greater China rights include aficamten, etripamil, varenicline solution nasal spray/US brand name TYRVAYA®, and LNZ100.
For further information about CORXEL, please visit www.corxelbio.com.
Cytokinetics is a late-stage, specialty cardiovascular biopharmaceutical company focused on discovering, developing and commercializing muscle biology-directed drug candidates as potential treatments for debilitating diseases in which cardiac 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 myocardial muscle function and contractility.
Following positive results from SEQUOIA-HCM, the pivotal Phase 3 clinical trial in obstructive hypertrophic cardiomyopathy, Cytokinetics submitted an NDA to the U.S. Food & Drug Administration and is progressing regulatory submissions for aficamten for the treatment of oHCM in Europe. Aficamten is also currently being evaluated in MAPLE-HCM, a Phase 3 clinical trial of aficamten as monotherapy compared to metoprolol as monotherapy in patients with obstructive HCM, ACACIA-HCM, a Phase 3 clinical trial of aficamten in patients with non-obstructive HCM, CEDAR-HCM, a clinical trial of aficamten in a pediatric population with obstructive HCM, and FOREST-HCM, an open-label extension clinical study of aficamten in patients with HCM.
Cytokinetics is also developing omecamtiv mecarbil, a cardiac muscle activator, in patients with heart failure. Additionally, Cytokinetics is developing CK-586, a cardiac myosin inhibitor with a mechanism of action distinct from aficamten for the potential treatment of HFpEF.
For additional information about Cytokinetics, visit www.cytokinetics.com and follow on X, LinkedIn, Facebook and YouTube.
