Results from VALOR-HCM LTE (56 weeks) demonstrated that with longer follow-up, CAMZYOS continued to reduce eligibility for invasive SRT at 56 weeks

EXPLORER-LTE data (cumulative analysis up to 120 weeks) showed sustained improvements in LVOT obstruction, symptoms, and NT-proBNP levels in patients with symptomatic obstructive HCM, with no new safety signals observed

CAMZYOS was recently approved in the European Union, following its approval in the U.S. and other markets worldwide, and is the first and only cardiac myosin inhibitor approved to treat adult patients with symptomatic obstructive HCM

PRINCETON, N.J.--(BUSINESS WIRE)-- Bristol Myers Squibb (NYSE: BMY) today announced new long-term follow-up results from two Phase 3 studies evaluating CAMZYOS® (mavacamten), a first-in-class cardiac myosin inhibitor, in adult patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM). Results from the 56-week analysis of the VALOR-HCM long-term extension (LTE) study were presented as a late-breaking oral presentation, with simultaneous publication in JAMA Cardiology, and results from the cumulative 120-week analysis of the EXPLORER cohort of the MAVA-LTE study were presented as an oral presentation at the European Society of Cardiology (ESC) Congress 2023.

“The new long-term data presented at ESC 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, M.D., Vice President, Head of Cardiomyopathy and Heart Failure Clinical Development, Bristol Myers Squibb. “These positive data reinforce the clinically meaningful significance of these two Phase 3 trials that led to the approval of CAMZYOS in the United States, the European Union and other countries around the globe. We are excited for the ongoing exploration of the potential of CAMZYOS and remain dedicated to providing support for obstructive HCM patients worldwide.”

Key findings from the 56-week analysis of VALOR-HCM LTE include:

• Treatment with CAMZYOS demonstrated sustained improvements across key study endpoints in both the original CAMZYOS group over 56 weeks and those transitioned to the placebo cross-over group over 40 weeks.
  • At Week 56, 5 of 56 patients (8.9%) in the original CAMZYOS group and 10 of 52 patients (19.2%) in the placebo cross-over group at Week 40 decided to proceed with septal reduction therapy (SRT) or were SRT-eligible.
  • CAMZYOS demonstrated sustained reduction in peak resting LVOT gradient (-34.0 mmHg for the original CAMZYOS group [95% CI -43.5 to -24.5] and -33.2 mmHg for the placebo cross-over group [95% CI -41.9 to -24.5]).
  • Proportion with NYHA class improvement of ≥1 class was observed in 93% of patients in the original CAMZYOS group at Week 56 and 73% of patients from the placebo cross-over group at Week 40.
  • On the patient-reported 23-item Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-23 CSS)*, average scores of symptom frequency, symptom burden and physical limitation continued to improve with a 14.1 point increase for the original CAMZYOS group (95% CI 9.9 to 18.3) and 11.7 point increase for the placebo crossover group (95% CI 6.9 to 16.4).
  • CAMZYOS was also associated with sustained reduction across biomarkers of cardiac wall stress and myocardial injury including reduction in N-terminal pro brain natriuretic peptide (NT-proBNP), with -376 ng/L for the original CAMZYOS group (95% CI -723 to -225) and -423 ng/L for the placebo cross-over group (95% CI -624 to -252) and reduction in cardiac troponin I with -7.0 ng/L for the original CAMZYOS group (95% CI -10 to -2.3) and -6.2 ng/L for the placebo cross-over group (95% CI -11.5 to -3.3).
  • No new safety signals were observed, and safety and efficacy were consistent across both patient groups.

*The KCCQ‑23 CSS is derived from the Total Symptom Score (TSS) and the Physical Limitations (PL) score of the KCCQ‑23. The CSS ranges from 0 to 100 with higher scores representing better health status.

“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, M.D., MBA, director, center for hypertrophic cardiomyopathy and vice chair of education in the Heart, Vascular & Thoracic Institute at Cleveland Clinic. “These findings are important for our continued understanding of this treatment and encouraging for patients hoping for non-surgical options.”

Key findings from the cumulative 120-week analysis of EXPLORER-LTE include:

• No new safety signals were observed.
• Overall, 75.9% of patients improved by ≥1 NYHA class from baseline at the start of the LTE study to Week 120.
  • Of the 14 patients who were in NYHA class I, 12 remained in NYHA class I at the latest available assessment.
• Treatment with CAMZYOS 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 LVEF remained within the normal range at all study visits.
  • Since the previous interim analysis in August 2021, one new patient experienced a transient reduction in LVEF 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 (HCM) to improve functional capacity and symptoms, and in the European Union, indicated for the treatment of symptomatic (NYHA, class II-III) obstructive HCM in adult patients. It has also received regulatory approvals in Australia, Brazil, Canada, Great Britain, Macau, Singapore, South Korea and Switzerland. 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.

    IMPORTANT SAFETY INFORMATION

    WARNING: RISK OF HEART FAILURE

    CAMZYOS reduces left ventricular ejection fraction (LVEF) and can cause heart failure due to systolic dysfunction.

    Echocardiogram assessments of LVEF are required prior to and during treatment with CAMZYOS. Initiation of CAMZYOS in patients with LVEF