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Long-Term Follow-Up Data From Phase 3 Study of Camzyos (mavacamten) Underscores Established Efficacy and Safety Profile in Patients With Symptomatic Obstructive Hypertrophic Cardiomyopathy (oHCM)
- Cumulative analysis of data up to 3.5 years from EXPLORER-LTE showed consistent and sustained improvements in echocardiographic measures and symptoms, with no new safety signals observed
- CAMZYOS is the first and only approved cardiac myosin inhibitor that targets the source of symptomatic obstructive hypertrophic cardiomyopathy
- Cumulative analysis of data up to 3.5 years from EXPLORER-LTE showed consistent and sustained improvements in echocardiographic measures and symptoms, with no new safety signals observed
- CAMZYOS is the first and only approved cardiac myosin inhibitor that targets the source of symptomatic obstructive hypertrophic cardiomyopathy
Bristol Myers Squibb News
Not intended for UK and Ireland audiences
PRINCETON, N.J.-- Bristol Myers Squibb announced new long-term follow-up results from the EXPLORER-LTE cohort of the MAVA-Long-Term Extension (LTE) study evaluating CAMZYOS ® (mavacamten) in adult patients with New York Heart Association (NYHA) class II-III symptomatic obstructive hypertrophic cardiomyopathy (oHCM).
The long-term follow-up efficacy and safety data, presented at the European Society of Cardiology (ESC) Congress in London, reinforce the established efficacy and safety profile of CAMZYOS, a first-in-class cardiac myosin inhibitor. With inclusion in both the ESC and AHA/ACC clinical guidelines as a recommended option for when symptoms persist after first-line therapy, CAMZYOS is a standard of care for symptomatic oHCM.
Patients experienced consistent and sustained improvements in echocardiographic measures and biomarkers after up to 3.5 years (180 weeks) of continuous treatment, including 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. They also experienced an improvement in symptoms and functional capacity as measured by NYHA class and patient-reported outcomes, including most patients achieving NYHA class I. The safety profile of CAMZYOS for up to 3.5 years remained consistent with the established safety profile, with no new safety signals identified.
“The consistent and sustained improvements in multiple cardiac measures over more than three years with CAMZYOS shows that this therapy meets an important treatment need for patients with symptomatic obstructive HCM,” said Pablo García-Pavia, MD, PhD, head of the Inherited Cardiac Diseases and Heart Failure Unit at the Department of Cardiology of Hospital Universitario Puerta de Hierro and professor at the Spanish Cardiovascular Research Institute (CNIC) in Madrid, Spain. “These positive long-term data, together with the inclusion of CAMZYOS in ESC clinical guidelines for obstructive HCM, underscore the important role of this medicine in the long-term care of this lifelong condition that requires ongoing management.”
At the data cutoff, 211 of 231 patients who enrolled in MAVA-LTE, of which EXPLORER-LTE is a cohort, were on CAMZYOS; 185 and 99 patients had reached Week 156 and 180, respectively. Key findings from the EXPLORER-LTE data analysis showed sustained improvements from baseline to Weeks 156 and 180 in echocardiographic measures and biomarkers. In echocardiographic markers, patients experienced a reduction of 55.3 mmHg in Valsalva LVOT gradient at both Week 156 and 180 and a reduction of 40.2 mmHg and 40.3 mmHg in mean resting LVOT gradient at Week 156 and 180, respectively. Improvements from baseline to Weeks 144 and 180 were sustained in mean left atrial volume index, with patients experiencing a reduction of 3.5 mL/m2 and 5.5 mL/m2, respectively. The mean left ventricular ejection fraction (LVEF) decreased by 11% from baseline to Week 180, and the mean (63.9%) remained within normal range. Evaluation of biomarker data showed that median NT-proBNP levels decreased by 504 ng/L at Week 156 and 562 ng/L by Week 180.
At Week 180, most patients (66.3%) were NYHA class I. Overall, 108 patients (46.8%) achieved a complete response — defined as achieving NYHA class I and a Valsalva LVOT gradient of ≤30 mmHg during the study and retained a complete response until the data cutoff. Patient-reported outcomes as measured by the HCM Symptom Questionnaire (HCMSQ) found improvement in shortness of breath score from baseline with treatment during the first 12 weeks and was sustained through Weeks 156 and 180.
“These results, representing the longest duration of follow up of the Phase 3 EXPLORER study to date, further reinforce the established safety and efficacy profile of CAMZYOS,” said Roland Chen, MD , senior vice president and head of Immunology, Cardiovascular & Neuroscience (ICN) Development at Bristol Myers Squibb. “As the first and only approved cardiac myosin inhibitor for patients with symptomatic obstructive HCM and with thousands of patients around the world treated to date, CAMZYOS, which targets the source of symptomatic obstructive HCM, is redefining the treatment landscape for this patient population.”
The EXPLORER-LTE analysis found no new safety signals observed with CAMZYOS treatment. A total of 20 patients (8.7%) experienced transient reductions in LVEF <50%, all recovered to LVEF ≥50% following treatment interruption and 14 patients reinitiated treatment with CAMZYOS.
About the EXPLORER-HCM and MAVA-LTE Trials
The double-blind, randomized, placebo-controlled, parallel group EXPLORER-HCM Phase 3 trial ( NCT03470545 ) enrolled 251 adult patients with symptomatic (NYHA class II or III) obstructive hypertrophic cardiomyopathy (oHCM). All participants had measurable left ventricular ejection fraction (LVEF) ≥55% and at least one peak LVOT gradient ≥50 mmHg (at rest or with provocation at diagnosis); in addition, Valsalva LVOT gradient ≥30 mmHg at baseline was required at screening. Among study participants, 92% were on background therapies of a beta blocker or calcium channel blocker. The primary endpoint was a composite functional endpoint, assessed at 30 weeks, and was defined as the proportion of patients who achieved either improvement of mixed venous oxygen tension (pVO 2 ) by ≥1.5 mL/kg/min plus improvement in NYHA class by at least 1 or improvement of pVO 2 by ≥3.0 mL/kg/min plus no worsening in NYHA class. Key secondary endpoints included impact on exercise gradient LVOT, pVO 2 , NYHA class and Kansas City Cardiomyopathy Questionnaire (KCCQ) and Hypertrophic Cardiomyopathy Symptom Questionnaire (HCMSQ) at Week 30.
EXPLORER-LTE is a cohort of the MAVA-LTE study ( NCT03723655 ), an ongoing, dose-blinded, 5-year study of CAMZYOS in patients with symptomatic oHCM who completed the EXPLORER-HCM trial. All participants in the EXPLORER-LTE cohort started on 5 mg of CAMZYOS daily, and dose adjustments were made at Weeks 4, 8 and 12 based on site-read echocardiography measures of Valsalva LVOT gradient and LVEF only. Dose adjustment was also possible at Week 24 following site-read echocardiography assessment of post-exercise LVOT gradient. Subsequent to Week 24, dose adjustment was possible if site-read Valsalva LVOT gradient was >30 mmHg and LVEF ≥50%.
About CAMZYOS (mavacamten)
CAMZYOS ® (mavacamten) is the first and only cardiac myosin inhibitor approved in the U.S., indicated for the treatment of adults with symptomatic New York Heart Association (NYHA) class II-III obstructive hypertrophic cardiomyopathy (oHCM) to improve functional capacity and symptoms, and in the European Union, indicated for the treatment of symptomatic (NYHA, class II-III) oHCM in adult patients. It has also received regulatory approvals in countries and regions across five continents including Argentina, Australia, Brazil, Canada, China, Chile, Great Britain, Hong Kong, Israel, Macau, Singapore, South Korea, Switzerland, and the United Arab Emirates. CAMZYOS is an allosteric and reversible inhibitor selective for cardiac myosin. CAMZYOS modulates the number of myosin heads that can enter “on actin” (power-generating) states, thus reducing the probability of force-producing (systolic) and residual (diastolic) cross-bridge formation. Excess myosin actin cross-bridge formation and dysregulation of the super-relaxed state are mechanistic hallmarks of HCM. CAMZYOS shifts the overall myosin population towards an energy-sparing, recruitable, super-relaxed state. In HCM patients, myosin inhibition with CAMZYOS reduces dynamic left ventricular outflow tract (LVOT) obstruction and improves cardiac filling pressures.
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