CAMZYOS^® Demonstrated Significant Improvement Across All Secondary Endpoints vs Placebo in EXPLORER-HCM^1,2

CAMZYOS Significantly Reduced LVOT Obstruction vs Placebo^1,2

Mean change in post-exercise LVOT peak gradient from baseline to Week 30^1,2

LVOT obstruction was assessed by post-exercise LVOT peak gradient.
Treatment difference (95% CI): -35 mmHg (-43, -28);
P<0.0001

Guideline-based threshold for surgery 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 30^1,2

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.

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

Proportion of patients with ≥1 NYHA class improvement from baseline to Week 30^1,2

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

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

CI=confidence interval; NYHA=New York Heart Association; SD=standard deviation.

CAMZYOS Showed Significant Mean Improvement in KCCQ-23–CSS Score vs Placebo^1,2

Mean change in KCCQ-23–CSS (patient-reported total symptom score and physical limitations) from baseline to Week 30^1,2

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

KCCQ-23–clinical summary score: mean change from baseline over time¹

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 Placebo^1,2

Mean change in HCMSQ-SoB (patient-reported frequency and severity of shortness of breath) from baseline to Week 30^1,2

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

HCMSQ shortness of breath domain: mean change from baseline over time¹

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.

Exploratory Endpoint: Mean Change in NT-proBNP Over the 30-Week Treatment Period^1,2

The reduction in NT‑proBNP was 80% greater with CAMZYOS than for placebo. 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.³

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.