Mavacamten treatment for obstructive hypertrophic cardiomyopathy a clinical trial

Stephen B. Heitner, Daniel Jacoby, Steven Jay Lester, Anjali Owens, Andrew Wang, David Zhang, Joseph Lambing, June Lee, Marc Semigran, Amy J. Sehnert

Research output: Contribution to journalArticle

Abstract

Background: Mavacamten, an orally administered, small-molecule modulator of cardiac myosin, targets underlying bio-mechanical abnormalities in obstructive hypertrophic cardiomyopathy (oHCM). Objective: To characterize the effect of mavacamten on left ventricular outflow tract (LVOT) gradient. Design: Open-label, nonrandomized, phase 2 trial. (Clinical Trials.gov: NCT02842242) Setting: 5 academic centers. Participants: 21 symptomatic patients with oHCM. Intervention: Patients in cohort A received mavacamten, 10 to 20 mg/d, without background medications. Those in cohort B received mavacamten, 2 to 5 mg/d, with -blockers allowed. Measurements: The primary end point was change in postexercise LVOT gradient at 12 weeks. Secondary end points included changes in peak oxygen consumption (pVO2), resting and Valsalva LVOT gradients, left ventricular ejection fraction (LVEF), and numerical rating scale dyspnea score. Results: In cohort A, mavacamten reduced mean postexercise LVOT gradient from 103 mm Hg (SD, 50) at baseline to 19 mm Hg (SD, 13) at 12 weeks (mean change, 89.5 mm Hg [95% CI, 138.3 to 40.7 mm Hg]; P = 0.008). Resting LVEF was also reduced (mean change, 15% [CI, 23% to 6%]). Peak VO2 increased by a mean of 3.5 mL/kg/min (CI, 1.2 to 5.9 mL/kg/ min). In cohort B, the mean postexercise LVOT gradient decreased from 86 mm Hg (SD, 43) to 64 mm Hg (SD, 26) (mean change, 25.0 mm Hg [CI, 47.1 to 3.0 mm Hg]; P = 0.020), and mean change in resting LVEF was 6% (CI, 10% to 1%). Peak VO2 increased by a mean of 1.7 mL/kg/min (SD, 2.3) (CI, 0.03 to 3.3 mL/kg/min). Dyspnea scores improved in both cohorts. Mavacamten was well tolerated, with mostly mild (80%), moderate (19%), and unrelated (79%) adverse events. The most common adverse events definitely or possibly related to mavacamten were decreased LVEF at higher plasma concentrations and atrial fibrillation. Limitation: Small size; open-label design. Conclusion: Mavacamten can reduce LVOT obstruction and improve exercise capacity and symptoms in patients with oHCM.

Original languageEnglish (US)
Pages (from-to)741-748
Number of pages8
JournalAnnals of internal medicine
Volume170
Issue number11
DOIs
StatePublished - Jun 4 2019

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Hypertrophic Cardiomyopathy
Stroke Volume
Clinical Trials
Dyspnea
Cardiac Myosins
Ventricular Outflow Obstruction
Therapeutics
Oxygen Consumption
Atrial Fibrillation
Exercise

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Heitner, S. B., Jacoby, D., Lester, S. J., Owens, A., Wang, A., Zhang, D., ... Sehnert, A. J. (2019). Mavacamten treatment for obstructive hypertrophic cardiomyopathy a clinical trial. Annals of internal medicine, 170(11), 741-748. https://doi.org/10.7326/M18-3016

Mavacamten treatment for obstructive hypertrophic cardiomyopathy a clinical trial. / Heitner, Stephen B.; Jacoby, Daniel; Lester, Steven Jay; Owens, Anjali; Wang, Andrew; Zhang, David; Lambing, Joseph; Lee, June; Semigran, Marc; Sehnert, Amy J.

In: Annals of internal medicine, Vol. 170, No. 11, 04.06.2019, p. 741-748.

Research output: Contribution to journalArticle

Heitner, SB, Jacoby, D, Lester, SJ, Owens, A, Wang, A, Zhang, D, Lambing, J, Lee, J, Semigran, M & Sehnert, AJ 2019, 'Mavacamten treatment for obstructive hypertrophic cardiomyopathy a clinical trial', Annals of internal medicine, vol. 170, no. 11, pp. 741-748. https://doi.org/10.7326/M18-3016
Heitner, Stephen B. ; Jacoby, Daniel ; Lester, Steven Jay ; Owens, Anjali ; Wang, Andrew ; Zhang, David ; Lambing, Joseph ; Lee, June ; Semigran, Marc ; Sehnert, Amy J. / Mavacamten treatment for obstructive hypertrophic cardiomyopathy a clinical trial. In: Annals of internal medicine. 2019 ; Vol. 170, No. 11. pp. 741-748.
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abstract = "Background: Mavacamten, an orally administered, small-molecule modulator of cardiac myosin, targets underlying bio-mechanical abnormalities in obstructive hypertrophic cardiomyopathy (oHCM). Objective: To characterize the effect of mavacamten on left ventricular outflow tract (LVOT) gradient. Design: Open-label, nonrandomized, phase 2 trial. (Clinical Trials.gov: NCT02842242) Setting: 5 academic centers. Participants: 21 symptomatic patients with oHCM. Intervention: Patients in cohort A received mavacamten, 10 to 20 mg/d, without background medications. Those in cohort B received mavacamten, 2 to 5 mg/d, with -blockers allowed. Measurements: The primary end point was change in postexercise LVOT gradient at 12 weeks. Secondary end points included changes in peak oxygen consumption (pVO2), resting and Valsalva LVOT gradients, left ventricular ejection fraction (LVEF), and numerical rating scale dyspnea score. Results: In cohort A, mavacamten reduced mean postexercise LVOT gradient from 103 mm Hg (SD, 50) at baseline to 19 mm Hg (SD, 13) at 12 weeks (mean change, 89.5 mm Hg [95{\%} CI, 138.3 to 40.7 mm Hg]; P = 0.008). Resting LVEF was also reduced (mean change, 15{\%} [CI, 23{\%} to 6{\%}]). Peak VO2 increased by a mean of 3.5 mL/kg/min (CI, 1.2 to 5.9 mL/kg/ min). In cohort B, the mean postexercise LVOT gradient decreased from 86 mm Hg (SD, 43) to 64 mm Hg (SD, 26) (mean change, 25.0 mm Hg [CI, 47.1 to 3.0 mm Hg]; P = 0.020), and mean change in resting LVEF was 6{\%} (CI, 10{\%} to 1{\%}). Peak VO2 increased by a mean of 1.7 mL/kg/min (SD, 2.3) (CI, 0.03 to 3.3 mL/kg/min). Dyspnea scores improved in both cohorts. Mavacamten was well tolerated, with mostly mild (80{\%}), moderate (19{\%}), and unrelated (79{\%}) adverse events. The most common adverse events definitely or possibly related to mavacamten were decreased LVEF at higher plasma concentrations and atrial fibrillation. Limitation: Small size; open-label design. Conclusion: Mavacamten can reduce LVOT obstruction and improve exercise capacity and symptoms in patients with oHCM.",
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AU - Lester, Steven Jay

AU - Owens, Anjali

AU - Wang, Andrew

AU - Zhang, David

AU - Lambing, Joseph

AU - Lee, June

AU - Semigran, Marc

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N2 - Background: Mavacamten, an orally administered, small-molecule modulator of cardiac myosin, targets underlying bio-mechanical abnormalities in obstructive hypertrophic cardiomyopathy (oHCM). Objective: To characterize the effect of mavacamten on left ventricular outflow tract (LVOT) gradient. Design: Open-label, nonrandomized, phase 2 trial. (Clinical Trials.gov: NCT02842242) Setting: 5 academic centers. Participants: 21 symptomatic patients with oHCM. Intervention: Patients in cohort A received mavacamten, 10 to 20 mg/d, without background medications. Those in cohort B received mavacamten, 2 to 5 mg/d, with -blockers allowed. Measurements: The primary end point was change in postexercise LVOT gradient at 12 weeks. Secondary end points included changes in peak oxygen consumption (pVO2), resting and Valsalva LVOT gradients, left ventricular ejection fraction (LVEF), and numerical rating scale dyspnea score. Results: In cohort A, mavacamten reduced mean postexercise LVOT gradient from 103 mm Hg (SD, 50) at baseline to 19 mm Hg (SD, 13) at 12 weeks (mean change, 89.5 mm Hg [95% CI, 138.3 to 40.7 mm Hg]; P = 0.008). Resting LVEF was also reduced (mean change, 15% [CI, 23% to 6%]). Peak VO2 increased by a mean of 3.5 mL/kg/min (CI, 1.2 to 5.9 mL/kg/ min). In cohort B, the mean postexercise LVOT gradient decreased from 86 mm Hg (SD, 43) to 64 mm Hg (SD, 26) (mean change, 25.0 mm Hg [CI, 47.1 to 3.0 mm Hg]; P = 0.020), and mean change in resting LVEF was 6% (CI, 10% to 1%). Peak VO2 increased by a mean of 1.7 mL/kg/min (SD, 2.3) (CI, 0.03 to 3.3 mL/kg/min). Dyspnea scores improved in both cohorts. Mavacamten was well tolerated, with mostly mild (80%), moderate (19%), and unrelated (79%) adverse events. The most common adverse events definitely or possibly related to mavacamten were decreased LVEF at higher plasma concentrations and atrial fibrillation. Limitation: Small size; open-label design. Conclusion: Mavacamten can reduce LVOT obstruction and improve exercise capacity and symptoms in patients with oHCM.

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