At 16 weeks the primary and all secondary endpoints were reached. Of the patients treated with mavacamten, 82% had not undergone SRT and no longer met the criteria for SRT according to the 2011 ACC / AHA Guidelines compared with 23% of patients receiving placebo. Patients on the mavacamten arm also showed a decrease in left ventricular outflow (LVOT) grades, an improvement in the New York Heart Association (NYHA) classification, an improvement in quality of life measures, and a statistically significant improvement in cardiac biomarkers compared to his arm. placebo. No new security signals were observed. “VALOR-HCM is based on the findings of the Phase 3 EXPLORER-HCM trial and shows that mavacamten is an effective potential treatment option for people with severe symptomatic HCM obstruction who meet the SRT guidelines,” said Milind Desai, MD, MBA. , Director of the HCM Center and Director of Clinical Surgery, Heart, Vascular & Thoracic Institute, Cleveland Clinic. “The data presented today are clinically relevant and have been shown to be able to influence parameters leading to SRT suitability.” The main findings of Week 16 included:
The combined proportion of patients who underwent SRT before or after Week 16 and those who remained eligible for SRT was significantly lower in those receiving mavacamten than in those receiving placebo (17.9% [10/56] against 76.8% [43/56]; Pi<0.0001). The LVOT peak slope after exercise was significantly reduced in patients treated with placebo over mavacamten (mean values at Week 16 = 42.0 mmHg ± 30.0 mmHg versus 83.2 mmHg ± 36.4 mmHg due to reductions from baseline value with mavacamten by 16 mmHg -39. mmHg ± 28.8 mmHg with placebo). The proportion of patients who improved ≥1 NYHA Class was significantly higher with mavacamten versus placebo (62.5% [35/56] against 21.4% [12/56]; Pi<0.0001). In the 23-item Kansas City Cardiomyopathy Questionnaire (KCCQ-23 CSS) clinical summary score, mean symptom frequency, symptom exacerbation, and physical limitation were significantly improved in patients treated with mavac from the initial value: +10.4 ± 16.1 versus +1.9 ± 12.0; Pi<0.0001). Improvement in the biomarkers of cardiac wall stress and myocardial damage with placebo-treated mavacamten showed a 67% decrease in N-terminal prenatural brain peptide (NT-proBNP) which was 67% greater and a decrease in cardiac troponin I 47% higher (p <0.0001). Safety data do not show individuals discontinuing treatment due to left ventricular ejection fraction (LVEF) ≤30% and no individuals experiencing severe adverse events such as congestive heart failure, syncope, or sudden cardiac death. Two subjects had transient LVEF <50% and continued treatment at a lower dose after a short break.
“These results confirm the promising potential of mavacamten as an important treatment option for symptomatic patients with oHCM,” said Marie-Laure Papi, vice president and head of mavacamten development, Bristol Myers Squibb. In the Phase 3 study, patients with symptomatic obstructive HCM (NYHA Class III-IV or Class II with stress or near syncope) who met the criteria of the 2011 ACC / AHA Guideline and were referred for SRT were randomized 1: 1 in mavacamten (n = 56) or placebo (n = 56) for 16 weeks. Study participants remained consistent with the maximum tolerable baseline regimens, which included β-blockers, calcium channel blockers, and / or disopyramide administered as monotherapy or in combination. Echocardiograms were performed to assess the LVOT and LVEF gradient at baseline and during drug titration to guide dosing and evaluate safety at Weeks 4, 8, and 12. Change from baseline to SRT fitness, peak gradient Post-exercise LVOT, NYHA Class, KCCQ-23 CSS and biomarkers (NT-proBNP and cardiac troponin I) were analyzed at Week 16. Suitability for SRT was determined on the basis of NYHA Class III or Class IV and a slope of LVOT ≥ 50 mmHg at rest or with Valsalva exercise or exercise, or NYHA Class II with symptoms of syncope or near syncope and increased inclination. The NYHA classification ranges from I to IV, with Class I showing no symptoms and Class IV having symptoms at rest.1 The KCCQ-23 CCS is the mean score of clinical symptoms reported by the patient, including the frequency and lower extremity edema, fatigue and shortness of breath as well as physical limitations, including, for example, dressing, showering, walking and gardening.2 Scores are based on a scale from 0 (worst) to 100 (better), with a change of 5 points being considered clinically significant and ≥10 to 20 points being considered moderate to large improvement.3.4 About Trial Phase 3 VALOR-HCM VALOR-HCM (NCT04349072) is a randomized, double-blind, placebo-controlled, multicenter Phase 3 study of patients with symptomatic obstructive HCM (NYHA Class III-IV or NYHA Class II with exercise fusion or near fusion) for septal reduction therapy (SRT) and have been referred for invasive procedure. The study included 112 patients who were randomized on a 1: 1 basis to receive mavacamten or placebo. VALOR-HCM includes three 128-week treatment periods: a 16-week placebo-controlled period, a 16-week active treatment period where all patients will receive mavacamten, and a long 96-week extension period where all patients will continue to receive mavacamten . The main endpoint of VALOR-HCM is a combination of the number of patients who decide to proceed with SRT before or Week 16 and the number of patients who remain eligible for the SRT guideline (LVOT slope ≥50mmHg and NYHA Class III-IV or Class II with syncope) at Week 16 in the mavacamten group compared with the placebo group. Key secondary endpoints include impact on the LVOT, NYHA Class and Kansas City Cardiomyopathy Questionnaire (KCCQ) and cardiac biomarkers (NT-proBNP and cardiac troponin I) at Week 16. About Obstructive Hypertrophic Cardiomyopathy Obstructive hypertrophic cardiomyopathy (obstructive HCM) is a chronic, progressive disease in which excessive contraction of the heart muscle and reduced filling capacity of the left ventricle can impair blood flow to the rest of the body, leading to the development of debilitating symptoms and heart failure. HCM can be inherited and can develop at any age. Patients are usually diagnosed in their 40s or 50s and up to 50% of patients have an inherited predisposition. In obstructive HCM, which is the most common type of HCM, the left ventricular outflow tract (LVOT), where blood leaves the heart, is blocked by an enlarged heart muscle. As a result, obstructive HCM has also been associated with an increased risk of atrial fibrillation, stroke, heart failure and, although rare, sudden cardiac death. The most common cause of obstructive HCM is mutations in sarcoma heart muscle proteins. Obstructive HCM is estimated to affect 400,000-600,000 people worldwide, however many patients remain undiagnosed and / or asymptomatic. About Mavacamten Mavacamten is a first-class oral allosteric regulator of cardiac myosin that is being investigated for the treatment of symptomatic obstructive hypertrophic cardiomyopathy (HCM), a progressive disease that thickens the walls of the heart and makes the heart wall harder and harder. and filled with blood. It is a selective cardiac myosin inhibitor that targets the underlying pathophysiology of obstructive HCM. Mavacamten has been shown to reduce cardiac muscle contractility by inhibiting excessive myosin-actin transverse bridge formation leading to hypersynthesis, left ventricular hypertrophy, and decreased compliance. Based on data from the EXPLORER-HCM study, the company has a PDUFA date in the US on April 28, 2022. In clinical and preclinical studies, mavacamten steadily reduces cardiac wall stress biomarkers, reduces excessive cardiac contractility, increases diastolic compliance, and reduces left ventricular outflow (LVOT) grades. Mavacamten is a research treatment and has not been approved for use in any country. About Bristol Myers Squibb Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative drugs that help patients overcome serious diseases. For more information on Bristol Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube, Facebook and Instagram. Warning Statement on future statements This press release contains “statements for the future” within the meaning of the 1995 Private Securities Litigation Reform Act on, inter alia, research, development and commercialization of medicinal products. 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