Long-Term Follow-Up Data Show Consistent, Durable Response to Mavacamten in Patients With Obstructive Hypertrophic Cardiomyopathy


Results from the VALOR-HCM LTE trial at 56 weeks demonstrated that with longer follow-up, mavacamten continued to reduce patient eligibility for invasive septal reduction therapy.

Long-term follow-up data from a pair of phase 3 studies of mavacamten (Camzyos; Bristol Myers Squibb) showed consistent and durable responses in patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM).

Image credit: Siarhei | stock.adobe.com

Image credit: Siarhei | stock.adobe.com

Results from the VALOR-HCM LTE trial at 56 weeks demonstrated that with longer follow-up, mavacamten continued to reduce patient eligibility for invasive septal reduction therapy (SRT). Additionally, a cumulative analysis of the EXPLORER-LTE data up to 120 weeks showed sustained improvement in left ventricular outflow tract (LVOT) obstruction, symptoms, and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels, with no new safety signals observed.

Mavacamten is a first-in-class cardiac myosin inhibitor indicated for the treatment of adults with symptomatic New York Heart Association (NYHA) class 2-3 obstructive HCM to improve functional capacity and symptoms. It is an allosteric and reversible inhibitor selective for cardiac myosin and modulates the number of myosin heads that can enter power-generating states, thus reducing the probability of force-producing and residual cross-bridge formation.

“The new long-term data presented at [the European Society of Cardiology] were consistent with the primary analyses from each study, further underscoring the benefit our first-in-class therapy can provide to patients with symptomatic obstructive HCM,” said Amy Sehnert, MD, vice president and head of cardiomyopathy and heart failure clinical development at Bristol Myers Squibb, in a press release. “These positive data reinforce the clinically meaningful significance of these 2 phase 3 trials that led to the approval of Camzyos in the United States, the European Union, and other countries around the globe.”

In the VALOR-HCM LTE 56-week analysis, treatment with mavacamten demonstrated sustained improvements across key study endpoints in both the original treatment group and in those who transitioned to the placebo crossover group over 40 weeks. At week 56, 8.9% of patients in the original mavacamten group and 19.2% in the placebo crossover group at week 40 decided to proceed with SRT or were SRT-eligible.

Mavacamten demonstrated sustained reduction in peak resting LVOT gradient, with -34.0 mmHg for the original treatment group and -33.2 mmHg in the placebo crossover group. Additionally, 93% of patients in the original treatment group and 73% in the placebo crossover group had NYHA class improvement of 1 class or more at week 40.

On the patient-reported, 23-item Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-23 CSS), average scores of symptom frequency, burden, and physical limitation continued to improve with a 14.1-point increase for the original mavacamten group and 11.7-point increase in the placebo crossover group.

No new safety signals were observed, and safety and efficacy were consistent across both patient groups.

“The 56-week late-breaking analysis of VALOR-HCM LTE builds upon previous findings and demonstrates the consistent impact of this oral treatment for severely symptomatic obstructive HCM patients by showing that nearly 9 out of 10 patients treated with this drug have continued in this long-term extension trial without SRT at either 40 or 56 weeks of treatment,” said Milind Desai, MD, MBA, director of the Center for Hypertrophic Cardiomyopathy and vice chair of education in the Heart, Vascular, and Thoracic Institute at Cleveland Clinic, in a press release. “These findings are important for our continued understanding of this treatment and encouraging for patients hoping for non-surgical options.”

In the cumulative 120-week analysis of EXPLORER-LTE, 75.9% of patients improved by 1 or more NYHA classes from baseline at the start of the LTE study to week 120. Of the 14 patients who were in NYHA class 1, a total of 12 remained in NYHA class 1 at the latest available assessment.

Treatment with mavacamten was associated with sustained improvements from baseline at the start of the LTE study in echocardiographic parameters, including E/e’ average and NT-proBNP. Mean left ventricular ejection fraction (LVEF) remained within the normal range at all study visits. Since the previous interim analysis in August 2021, there was 1 new patient who experienced a transient reduction in LVEF <50% resulting in temporary treatment interruption.

“The presentation of data—the largest and longest analysis of patients on Camzyos to-date—illustrates the promise of this game-changing treatment for patients with symptomatic obstructive HCM,” said Pablo Garcia-Pavia, MD, PhD, head of the Inherited Cardiac Diseases and Heart Failure Unit at the Department of Cardiology of Hospital Universitario Puerta de Hierro in Madrid, Spain, in the press release. “Studies like EXPLORER-LTE are important for understanding longer-term results that assess key cardiac measures and support the use of Camzyos in patients living with this chronic condition.”


Long-Term Follow-Up Data from Two Phase 3 Studies of Camzyos (mavacamten) Demonstrate Consistent and Durable Response in Patients with Symptomatic Obstructive Hypertrophic Cardiomyopathy (HCM). News release. Bristol Myers Squibb. August 28, 2023. Accessed August 30, 2023. https://news.bms.com/news/corporate-financial/2023/Long-Term-Follow-Up-Data-from-Two-Phase-3-Studies-of-CAMZYOS-mavacamten-Demonstrate-Consistent-and-Durable-Response-in-Patients-with-Symptomatic-Obstructive-Hypertrophic-Cardiomyopathy-HCM/default.aspx

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