- EXPLORER-CN data presented in oral late-breaking science session at ESC 2023
- Data from the trial published simultaneously in JAMA Cardiology
- Mavacamten demonstrated improvement in Valsalva LVOT peak gradient, LVOT obstruction, clinical symptoms, health status, cardiac biomarkers, and cardiac structure in Chinese oHCM patients
- Study confirms previously established efficacy of mavacamten can be extended to Chinese patients
The data presented at ESC 2023 and published in JAMA Cardiology continue to demonstrate robust evidence of mavacamten’s therapeutic benefit. New data published today provide additional detail showing mavacamten’s impact on reducing cardiac biomarkers associated with poor prognosis in oHCM, and improvement in biomarkers associated with cardiac structure remodeling. In addition, the study demonstrated mavacamten’s efficacy across prespecified subgroups, including beta-blocker usage, sex, age, body mass index,
“EXPLORER-CN demonstrates mavacamten’s broad treatment effect in oHCM,” said
The randomized, controlled, Phase 3 EXPLORER-CN trial enrolled 81 patients with symptomatic oHCM. All patients had significant LVOT obstruction at baseline. The mean left ventricular ejection fraction (LVEF) was similar between the mavacamten and placebo groups. Most patients were receiving background beta-blockers in both groups.
As previously reported, EXPLORER-CN met its primary endpoint, demonstrating a statistically significant and clinically meaningful improvement in Valsalva LVOT peak gradient compared to placebo after 30 weeks of treatment (least-squares mean difference, −70.29 mm Hg; 95% CI, −89.64 to −50.94; 1-sided p< .001). The reduction in Valsalva LVOT peak gradient with mavacamten treatment started as early as 4 weeks and was sustained through week 30. Data published today showed consistent benefit for the primary endpoint was observed across prespecified subgroups, regardless of beta-blocker use or CYP2C19 phenotype.
Among the new data published today, cardiac biomarkers decreased with mavacamten treatment from week 4 and were sustained throughout the study period. At week 30, reduction in N-terminal pro-B-type natriuretic peptide (NT-proBNP) was 82% greater for mavacamten compared with placebo (proportion of geometric mean ratio [GMR], 0.18; 95% CI, 0.13 to 0.24). Reduction in high-sensitivity cardiac troponin I (hs-cTnI) was 66% greater in the mavacamten group compared with placebo (proportion of GMR, 0.34; 95% CI, 0.27 to 0.42). NT-proBNP and cardiac troponin are biomarkers of cardiac wall stress and myocardial injury that have been associated with poor clinical outcomes, including heart failure, atrial fibrillation, and death in HCM patients.
Improvements in cardiac structure were also observed in patients treated with mavacamten. Among 58 eligible patients with cardiac magnetic resonance (CMR) data available, secondary and exploratory CMR endpoints revealed favorable markers for cardiac remodeling with mavacamten from baseline to week 30, including reductions in left ventricular mass index (LVMI) (mean difference, −30.80 g/m2; 95% CI, −41.55 to −20.05), left ventricular mass (mean difference, −52.64 g; 95% CI, −67.89 to −37.39), maximum left atrial volume index (mean difference, −18.27 mL/m2; 95% CI, −26.72 to −9.83), and left ventricular maximal wall thickness (mean difference, −3.52 mm; 95% CI, −4.65 to −2.38), all of which are predictors of poor outcomes in oHCM.
As previously reported, safety results in the trial were consistent with previous studies of mavacamten in symptomatic oHCM, and no new safety signals were reported. Resting LVEF remained stable in both groups throughout treatment, and no participants in the study experienced decreases in LVEF <50 % that required dose interruption.
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“Mavacamten is the first pharmacological tool developed to specifically target the underlying pathophysiology of oHCM in China,” said
About Mavacamten
Camzyos® (mavacamten) is the first and only cardiac myosin inhibitor approved by the
About EXPLORER-CN
The Phase 3 EXPLORER-CN trial enrolled a total of 81 Chinese patients with symptomatic (NYHA Class II or III) oHCM. All participants had one measurable LVOT gradient (resting or Valsalva) >50 mmHg during screening. Patients were randomized 2:1 to mavacamten or placebo.
The primary endpoint for EXPLORER-CN is the change from baseline to week 30 in Valsalva LVOT peak gradient. Secondary endpoints include change from baseline to week 30 in resting LVOT peak gradient, proportion of participants achieving a Valsalva LVOT peak gradient <30 mmHg at week 30, proportion of participants achieving a Valsalva LVOT peak gradient <50 mmHg at week 30, proportion of participants with at least one NYHA class improvement from baseline to week 30, change from baseline to week 30 in Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical Summary Score (CSS), change from baseline to week 30 in NT-proBNP, change from baseline to week 30 in cardiac troponin, and change from baseline to week 30 in left ventricular mass index evaluated by cardiac magnetic resonance imaging.
More information about the EXPLORER-CN trial can be found on ClinicalTrials.gov (NCT05174416) or http://www.chinadrugtrials.org.cn/index.html (CTR20212890).
About Hypertrophic Cardiomyopathy
Hypertrophic cardiomyopathy (HCM) is a chronic, progressive disease in which excessive contraction of the heart muscle and reduced ability of the left ventricle to fill can lead to the development of debilitating symptoms and cardiac dysfunction. HCM is estimated to affect one in every 500 people globally. The most frequent cause of HCM is mutations in the heart muscle proteins of the sarcomere. In patients with both obstructive and non-obstructive HCM, exertion can result in fatigue or shortness of breath, interfering with a patient’s ability to participate in activities of daily living. HCM has also been associated with increased risks of atrial fibrillation, stroke, heart failure and sudden cardiac death.
In
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