Long-Term Follow-Up of Phase 3 Study Highlights Efficacy and Safety of Camzyos in Symptomatic Obstructive Hypertrophic Cardiomyopathy
An extensive analysis of data from the EXPLORER-LTE study over 3.5 years demonstrates the sustained efficacy and safety of Camzyos in treating patients with symptomatic obstructive hypertrophic cardiomyopathy (oHCM), with no new safety concerns emerging.
Camzyos remains the only approved cardiac myosin inhibitor directly addressing the underlying cause of symptomatic oHCM.
Bristol Myers Squibb recently shared updated long-term follow-up data from the EXPLORER-LTE cohort within the MAVA-Long-Term Extension (LTE) study, which focuses on Camzyos (mavacamten) in adult patients with New York Heart Association (NYHA) class II-III symptomatic obstructive hypertrophic cardiomyopathy (oHCM).
The long-term efficacy and safety findings, presented at the in London, reinforce the established efficacy and safety profile of Camzyos. As a pioneering cardiac myosin inhibitor, Camzyos is recommended in both ESC and AHA/ACC clinical guidelines for patients with persistent symptoms after initial treatments, making it a standard of care for symptomatic oHCM.
Patients exhibited consistent and sustained improvements in echocardiographic parameters and biomarkers over up to 3.5 years (180 weeks) of continuous treatment. These improvements included reductions in resting left ventricular outflow tract (LVOT) gradient, Valsalva LVOT gradient, left atrial volume index, and N-terminal pro B-type natriuretic peptide (NT-proBNP) levels. Additionally, patients showed enhanced symptoms and functional capacity, with the majority achieving NYHA class I status. The safety profile of Camzyos over this period remained consistent with previous findings, with no new safety issues detected.
At the time of data cutoff, 211 of the 231 patients enrolled in MAVA-LTE, of which EXPLORER-LTE is a subset, were receiving Camzyos; 185 patients had reached Week 156, and 99 had reached Week 180. Key results from the EXPLORER-LTE analysis revealed sustained improvements from baseline to Weeks 156 and 180 in both echocardiographic measures and biomarkers.
Specifically, patients experienced a reduction of 55.3 mmHg in Valsalva LVOT gradient at both Week 156 and 180, and a decrease of 40.2 mmHg and 40.3 mmHg in mean resting LVOT gradient at Week 156 and 180, respectively.
Additionally, the mean left atrial volume index showed sustained reductions from baseline to Weeks 144 and 180, with decreases of 3.5 mL/m² and 5.5 mL/m², respectively. The mean left ventricular ejection fraction (LVEF) saw an 11% decrease from baseline to Week 180, with the average (63.9%) remaining within the normal range. Biomarker analysis revealed that median NT-proBNP levels dropped by 504 ng/L at Week 156 and 562 ng/L by Week 180.
At Week 180, the majority of patients (66.3%) were classified as NYHA class I. Furthermore, 108 patients (46.8%) achieved a complete response, defined as reaching NYHA class I and a Valsalva LVOT gradient of ≤30 mmHg during the study, maintaining this response through the data cutoff. Patient-reported outcomes, as measured by the HCM Symptom Questionnaire (HCMSQ), indicated improvements in shortness of breath scores from baseline, sustained through Weeks 156 and 180.
About the EXPLORER-HCM and MAVA-LTE Trials
The EXPLORER-HCM Phase 3 trial (NCT03470545), a double-blind, randomized, placebo-controlled study, included 251 adult patients with symptomatic (NYHA class II or III) obstructive hypertrophic cardiomyopathy (oHCM). All participants had a measurable left ventricular ejection fraction (LVEF) ≥55% and at least one peak LVOT gradient ≥50 mmHg (either at rest or with provocation at diagnosis). Additionally, a baseline Valsalva LVOT gradient of ≥30 mmHg was required at screening. Among the participants, 92% were on background therapies such as beta blockers or calcium channel blockers. The primary endpoint, assessed at 30 weeks, was a composite functional measure, defined as the proportion of patients achieving either an improvement in mixed venous oxygen tension (pVO₂) by ≥1.5 mL/kg/min along with an improvement in NYHA class by at least one level, or an improvement in pVO₂ by ≥3.0 mL/kg/min without worsening NYHA class. Secondary endpoints included the impact on exercise LVOT gradient, pVO₂, NYHA class, and scores on the Kansas City Cardiomyopathy Questionnaire (KCCQ) and Hypertrophic Cardiomyopathy Symptom Questionnaire (HCMSQ) at Week 30.
The EXPLORER-LTE is a cohort within the ongoing MAVA-LTE study (NCT03723655), a 5-year, dose-blinded study of Camzyos in symptomatic oHCM patients who completed the EXPLORER-HCM trial. Participants in EXPLORER-LTE began with a daily dose of 5 mg of Camzyos, with dose adjustments at Weeks 4, 8, and 12 based on echocardiography measures of Valsalva LVOT gradient and LVEF. Dose adjustments were also possible at Week 24, following echocardiography assessment of post-exercise LVOT gradient, and could continue if Valsalva LVOT gradient was >30 mmHg and LVEF ≥50% beyond Week 24.
About Camzyos (mavacamten)
Camzyos (mavacamten) is the first and only cardiac myosin inhibitor approved in the U.S. for treating adults with symptomatic New York Heart Association (NYHA) class II-III obstructive hypertrophic cardiomyopathy (oHCM) to enhance functional capacity and alleviate symptoms. It has also been approved in the European Union for treating symptomatic (NYHA class II-III) oHCM in adults. Additionally, Camzyos has received regulatory approvals across several countries and regions, including Argentina, Australia, Brazil, Canada, China, Chile, Great Britain, Hong Kong, Israel, Macau, Singapore, South Korea, Switzerland, and the United Arab Emirates.
Camzyos functions as an allosteric, reversible inhibitor selective for cardiac myosin, modulating the number of myosin heads that can enter "on actin" (power-generating) states. This modulation decreases the likelihood of force-producing (systolic) and residual (diastolic) cross-bridge formation, mechanisms characteristic of hypertrophic cardiomyopathy (HCM). Camzyos shifts the overall myosin population towards a more energy-efficient, recruitable, super-relaxed state. In patients with HCM, myosin inhibition by Camzyos reduces dynamic left ventricular outflow tract (LVOT) obstruction and improves cardiac filling pressures.
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