Bristol Myers Squibb Announces Long-Term Follow-Up Data from Two Phase 3 Trials of First-in-Class CAMZYOS® (mavacamten) in Symptomatic Obstructive Hypertrophic Cardiomyopathy

▎Edited by the WuXi AppTec content team

Recently, Bristol Myers Squibb Company announced the latest long-term follow-up results of two Phase 3 studies evaluating Camzyos (mavacamten) for the treatment of adults with symptomatic obstructive hypertrophic cardiomyopathy (oHCM).The results showed that, with the extension of follow-up time, Camzyos continued to reduce the proportion of patients requiring invasive septal reduction therapy (SRT) at 56 weeks. The cumulative analysis results over 120 weeks showed sustained improvements in LVOT obstruction, symptoms, and NT-proBNP levels in symptomatic oHCM patients, with no new safety signals observed.

oHCM is a chronic progressive disease that can cause the heart walls to thicken, making it difficult for the heart to expand properly and fill with blood. This leads to various debilitating symptoms and cardiac dysfunction and is also a common cause of sudden cardiac arrest in young individuals. The most frequent cause of oHCM is mutations in the myocardial proteins of the sarcomere. In patients with oHCM, the left ventricular outflow tract (LVOT), through which blood exits the heart, is obstructed by thickened myocardium. As a result, the disease is also associated with an increased risk of atrial fibrillation, stroke, heart failure, and sudden death. Many patients suffering from severe symptomatic oHCM are often advised to undergo SRT. This typically requires patients to undergo open-heart surgery or septal myectomy, both of which carry certain risks and require specialized care. Therefore, there is an urgent need for new alternative therapies to treat patients with oHCM.

Camzyos is an innovative oral selective cardiac myosin allosteric modulator that targets the underlying pathophysiology of oHCM, with the potential to reduce excessive cardiac contraction symptoms in patients.In clinical and preclinical studies, Camzyos can reduce biomarkers of cardiac wall stress, alleviate excessive myocardial contractility, decrease LVOT gradient, and increase diastolic compliance.Previously, Camzyos had received U.S. FDA approval.Approval, becoming the "first-in-class" cardiac myosin allosteric inhibitor for improving heart function and alleviating symptoms in adult patients with oHCM,These patients were rated as Class 2 or 3 according to the New York Heart Association (NYHA) Functional Classification.

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The 56-week analysis results of the VALOR-HCM Long-Term Extension (LTE) study announced this time are as follows:

• After 56 weeks of treatment with Camzyos, patients in the original Camzyos group and those who switched to the placebo crossover group after 40 weeks continued to show improvement in key study endpoints.At Week 56, 5 of 56 patients (8.9%) in the original Camzyos group decided to continue or were eligible to receive SRT, and at Week 40, 10 of 52 patients (19.2%) in the placebo crossover group decided to continue receiving SRT.

• Camzyos can continuously reduce the peak resting LVOT gradient (the original Camzyos group: -34.0 mmHg [95% CI, -43.5 to -24.5]; the placebo crossover group: -33.2 mmHg [95% CI, -41.9 to -24.5]).

• At Week 56, 93% of patients in the original Camzyos group had an improvement of ≥1 grade in NYHA class, and at Week 40, 73% of patients in the placebo crossover group had an improvement of ≥1 grade in NYHA class.

• In the patient-reported 23-item Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-23 CSS), the average scores for symptom frequency, symptom burden, and physical limitations continued to improve (higher scores indicate better health status).The original Camzyos group increased by 14.1 points (95% CI, 9.9 to 18.3), while the placebo crossover group increased by 11.7 points (95% CI, 6.9 to 16.4).

• Camzyos can also continuously reduce biomarkers of myocardial wall stress and myocardial injury.Including the reduction of N-terminal pro-brain natriuretic peptide (NT-proBNP), the original Camzyos group showed a decrease of -376 ng/L (95% CI, -723 to -225), and the placebo crossover group showed a decrease of -423 ng/L (95% CI, -624 to -252); the reduction of cardiac troponin I, the original Camzyos group showed a decrease of -7.0 ng/L (95% CI, -10 to -2.3), and the placebo crossover group showed a decrease of -6.2 ng/L (95% CI, -11.5 to -3.3).

• No new safety signals were observed, and the safety and efficacy were consistent between the two groups.

The 120-week cumulative analysis results of the EXPLORER cohort from the recently published MAVA-LTE study show:

• No new safety signals were observed.

• Overall, from the start of LTE research to Week 120, 75.9% of patients experienced an improvement of ≥1 grade in NYHA classification.Of the 14 patients with NYHA Class 1, 12 remained Class 1 at the latest assessment.

• After receiving Camzyos treatment, the patients' echocardiographic parameters (including the average E/e' and NT-proBNP) showed continuous improvement compared to the baseline values at the start of the LTE study.

• The average left ventricular ejection fraction (LVEF) for all study visits remained within the normal range.Since the last interim analysis in August 2021, one new patient experienced a transient decrease in LVEF.

Following its approval in the United States and other countries and regions around the world, Camzyos has now been approved in the European Union.The press release noted that Camzyos is the first cardiac myosin inhibitor approved for the treatment of symptomatic oHCM in adult patients.

References:

[1] 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). Retrieved August 29, 2023 from https://www.businesswire.com/news/home/20230828341879/en