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For patients with NYHA class II–III obstructive HCM,

In EXPLORER-HCM, CAMZYOS® Demonstrated Significant Improvement Across the Primary Endpoint and All Secondary Endpoints vs Placebo1,2

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EXPLORER-HCM: Primary Composite Functional Endpoint

CAMZYOS® Demonstrated Significant Benefit in the Primary Composite Functional Endpoint vs Placebo1,2

Primary composite functional endpoint: Proportion of patients with decreased symptom burden and increased functional capacity at Week 301,2

The primary composite functional endpoint was defined as achieved with an improvement of pVO2 by 1.5 mL/kg/min or more and improvement in NYHA class by at least 1 or an improvement of pVO2 by 3.0 mL/kg/min or more and no worsening in NYHA class.1

Treatment difference (95% CI): 19% (9, 30);
P=0.0005

Primary Endpoint CAMZYOS® (mavacamten) vs Placebo, Chart Primary Endpoint CAMZYOS® (mavacamten) vs Placebo, Chart

CI=confidence interval; NYHA=New York Heart Association; pVO2=peak oxygen consumption.

EXPLORER-HCM: LVOT Obstruction

CAMZYOS Significantly Reduced LVOT Obstruction vs Placebo1,2

Secondary endpoint: Mean change in post-exercise LVOT peak gradient from baseline to Week 301,2

LVOT obstruction was assessed by post-exercise LVOT peak gradient.

Treatment difference (95% CI): -35 mmHg (-43, -28);
P<0.0001

Secondary Endpoint LVOT Mean Change CAMZYOS® (mavacamten) vs Placebo, Chart Secondary Endpoint LVOT Mean Change CAMZYOS® (mavacamten) vs Placebo, Chart

Guideline-based threshold for SRT consideration (>50 mmHg)2

Guideline-based diagnostic criteria for obstruction (>30 mmHg)2

Data based on all randomized patients who received ≥1 dose of study treatment. LVOT gradient was analyzed with all available data without imputation.2

Exploratory endpoints: Proportion of patients achieving post-exercise LVOT peak gradient <50 mmHg or <30 mmHg at Week 301,2

While these exploratory endpoints were prespecified, they were not powered for significance.3

  • *Only patients with baseline post-exercise LVOT peak gradient of at least 50 mmHg were assessed.2
  • Only patients with baseline post-exercise LVOT peak gradient of at least 30 mmHg were assessed.2
  • LVOT=left ventricular outflow tract.

EXPLORER-HCM: NYHA Class

Significantly More Patients Improved by ≥1 NYHA Class With CAMZYOS vs Placebo1,2

Secondary endpoint: Proportion of patients with ≥1 NYHA class improvement from baseline to Week 301,2

Treatment difference (95% CI): 34% (22, 45);
P<0.0001

CAMZYOS® (mavacamten) vs Placebo NYHA class improvement from baseline to week 30, Graphic CAMZYOS® (mavacamten) vs Placebo NYHA class improvement from baseline to week 30, Graphic

At baseline, approximately 73% of the randomized patients were NYHA class II and 27% were NYHA class III.1

Data based on all randomized patients who received ≥1 dose of study treatment. Missing NYHA class data at Week 30 were imputed with the Week 26 value for NYHA response. Patients with a nonevaluable NYHA secondary endpoint were considered nonresponders.2

Given the secondary endpoints in EXPLORER-HCM are hierarchical in nature, the endpoint related to NYHA class presented here is subsequent to significance achieved for the endpoint related to pVO2. The difference in mean change (SD) of pVO2 from baseline to Week 30 was 1.4 (3.1) mL/kg/min in the CAMZYOS group vs -0.1 (3) mL/kg/min in the placebo group, treatment difference, 1.4 mL/kg/min; 95% CI (0.6, 2.1), P<0.0006.1,2

Exploratory endpoints: NYHA class changes from baseline to Week 30 in CAMZYOS and placebo2

The data below were used to calculate the secondary endpoint related to NYHA class but were exploratory in nature and not evaluated for significance to compare between the treatment groups.2,3

Data used to Calculate Secondary Endpoint  NYHA Class Changes CAMZYOS® (mavacamten) vs Placebo, Chart Data used to Calculate Secondary Endpoint  NYHA Class Changes CAMZYOS® (mavacamten) vs Placebo, Chart

EXPLORER-HCM: Patient-Reported Outcomes

CAMZYOS Showed Significant Mean Improvement in KCCQ-23–CSS Score vs Placebo1,2

Secondary endpoint: Mean change in KCCQ-23–CSS (patient-reported symptom score and physical limitations) from baseline to Week 301,2

Treatment difference: (95% CI): 9 (5, 13);
P<0.0001

KCCQ-23–clinical summary score: Mean change from baseline over time1
Secondary Endpoint KCCQ-23 Clinical Summary Mean Change CAMZYOS® (mavacamten) vs Placebo, Chart Secondary Endpoint KCCQ-23 Clinical Summary Mean Change CAMZYOS® (mavacamten) vs Placebo, Chart

Mean baseline KCCQ-23 CSS (SD) was 71 (16) for the CAMZYOS group (n=99) and 71 (19) for the placebo group (n=97).1

KCCQ-23 TSS: Change from baseline to Week 30, mean (SD) was 12 (15) for CAMZYOS and 5 (16) for placebo.1

KCCQ-23 PL: Change from baseline to Week 30, mean (SD) was 15 (17) for CAMZYOS and 4 (15) for placebo.1

The KCCQ-23–CSS is composed of the physical limitations and total symptom burden scores of the KCCQ-23. The Clinical Summary Score ranges from 0 to 100, with higher scores representing less severe symptoms and/or physical limitations.1

Missing data were not imputed to summarize the baseline and change from baseline to Week 30 values. Difference in mean change from baseline between treatment groups was estimated using a mixed model for repeated measures.1

Patient-reported outcomes were analyzed with all available data. Sensitivity analyses were conducted to assess the effect of the missing data. When missing data were imputed with unfavorable results for the CAMZYOS group, the estimated treatment effects of KCCQ-CSS remained significant (P<0.05).2

KCCQ-23–CSS=Kansas City Cardiomyopathy Questionnaire (23-item version)–Clinical Summary Score; LS=least square; PL=physical limitations; SE=standard error; TSS=total symptom score.

CAMZYOS Showed Significant Mean Improvement in HCMSQ-SoB vs Placebo1,2

Secondary endpoint: Mean change in HCMSQ-SoB (patient-reported frequency and severity of shortness of breath) from baseline to Week 301,2

Treatment difference (95% CI): -2 (-2, -1);
P<0.0001

HCMSQ shortness of breath domain: Mean change from baseline over time1
Exploratory Endpoint  HCMSQ-SoB Mean Change CAMZYOS® (mavacamten) vs Placebo, Chart Exploratory Endpoint  HCMSQ-SoB Mean Change CAMZYOS® (mavacamten) vs Placebo, Chart

Mean baseline HCMSQ-SoB domain score (SD) was 5 (3) for both CAMZYOS (n=108) and placebo (n=109) groups.1

The HCMSQ-SoB domain score measures the frequency and severity of shortness of breath. The HCMSQ-SoB scale score ranges from 0 to 18 with lower scores representing less shortness of breath.1

Missing data were not imputed to summarize the baseline and change from baseline to Week 30 values. Difference in mean change from baseline between treatment groups was estimated using a mixed model for repeated measures.1

Patient-reported outcomes were analyzed with all available data. Sensitivity analyses were conducted to assess the effect of the missing data. When missing data were imputed with unfavorable results for the CAMZYOS group, the estimated treatment effects of HCMSQ-SoB remained significant (P<0.05).2

HCMSQ-SoB=Hypertrophic Cardiomyopathy Symptom Questionnaire-Shortness of Breath subscore.

EXPLORER-HCM: Cardiac Biomarkers

CAMZYOS Reduced NT-proBNP, a Biomarker of Cardiac Wall Stress1

Exploratory endpoint: Mean change in NT-proBNP over the 30-week treatment period1,2

The reduction in NT-proBNP was 80% greater with CAMZYOS than for placebo.1,2,4 The clinical significance of these findings is unknown.1,2

Treatment difference (95% CI): 0.20 (0.17, 0.24)

While this endpoint was prespecified, it was not powered for significance.

Exploratory Endpoint NT-proBNP Mean Change CAMZYOS® (mavacamten) vs Placebo, Chart Exploratory Endpoint NT-proBNP Mean Change CAMZYOS® (mavacamten) vs Placebo, Chart

NT-proBNP is a marker for negative cardiac outcomes in patients with obstructive hypertrophic cardiomyopathy.4

NT-proBNP=N-terminal pro B-type natriuretic peptide.

The efficacy of CAMZYOS was evaluated in EXPLORER-HCM, a phase 3, double-blind, randomized, placebo-controlled trial that enrolled 251 adult patients with symptomatic (New York Heart Association [NYHA] class II and III) obstructive HCM, with left ventricular outflow tract (LVOT) peak gradient ≥50 mmHg, and left ventricle ejection fraction (LVEF) ≥55% at rest or with provocation.1 Patients were randomized in a 1:1 ratio to receive CAMZYOS (n=123) or placebo (n=128) once daily for 30 weeks.1

All subjects were initiated on CAMZYOS 5 mg (or matching placebo) once daily, and the dose was periodically adjusted to optimize patient response (decrease in LVOT gradient with Valsalva maneuver), maintain LVEF ≥50%, and was further informed by plasma concentrations of CAMZYOS.1,2

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References:

  1. CAMZYOS [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; 2023.
  2. Olivotto I, Oreziak A, Barriales-Villa R, et al; EXPLORER-HCM study investigators. Mavacamten for treatment of symptomatic obstructive hypertrophic cardiomyopathy (EXPLORER-HCM): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2020;396(10253):759-769. doi:10.1016/S0140-6736(20)31792-X
  3. Olivotto I. Efficacy and safety of mavacamten in adults with symptomatic obstructive hypertrophic cardiomyopathy: results of the EXPLORER-HCM study. Presented at ESC Congress The Digital Experience; 2020.
  4. Naidu SS, ed. Hypertrophic Cardiomyopathy. London, Eng: Springer-Verlag; 2015.
  5. Data on file. BMS-REF-MAVA-004. Princeton, NJ: Bristol-Myers Squibb Company; 2021.