BMS Announces Mavacamten Met All Primary and Secondary Endpoints in Phase 3 Trial for Obstructive Hypertrophic Cardiomyopathy

Recently, Bristol-Myers Squibb (BMS) Company announced the latest Phase 3 clinical trial results of mavacamten, a potential "first-in-class" cardiac myosin allosteric inhibitor, for the treatment of obstructive hypertrophic cardiomyopathy (oHCM). The trial results showed that mavacamten achieved all primary and secondary endpoints at 16 weeks of treatment. Moreover, in the long-term extension trial, mavacamten still provided clinically meaningful improvements in cardiovascular indicators after 48 weeks and 84 weeks of treatment. The new drug application for mavacamten is currently under review by the U.S. FDA, with a response expected this month. It has been listed by Evaluate as one of the potential blockbuster therapies expected to be approved this year.

oHCM is a chronic progressive disease that causes 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 it is also a common cause of sudden cardiac arrest in young people. The most common 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, creating an urgent need for new therapies to treat affected patients.

Mavacamten 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, mavacamten has been shown to decrease biomarkers of cardiac wall stress, reduce excessive myocardial contractility, lower LVOT gradients, and improve diastolic compliance. The U.S. FDA has granted mavacamten Breakthrough Therapy Designation.

Latest clinical trial results show that after 16 weeks of treatment, 17.9% of patients in the mavacamten group underwent further septal reduction therapy (SRT) or still met the criteria for SRT. This figure was 76.8% in the placebo group (p<0.0001). This indicates that mavacamten significantly reduced the need for further SRT in patients.

Long-term extended clinical results show that improvements in various tests related to cardiovascular health were maintained after 48 and 84 weeks of treatment. For example:

The resting LVOT gradient decreased by 35.6 mmHg ± 32.6 mmHg from baseline after 48 weeks of treatment, with a similar reduction maintained up to 84 weeks.

Serum NT-proBNP levels decreased by an average of 480 ng/L after 48 weeks of treatment. A similar reduction was maintained up to 84 weeks.

At 48 weeks, 67.5% of patients improved by more than one grade in the New York Heart Association (NYHA) functional classification compared to baseline.

"The results of the extended clinical trial support the long-term use of mavacamten in symptomatic oHCM patients," said Dr. Marie-Laure Papi, head of Bristol-Myers Squibb's mavacamten development program. "We look forward to the opportunity to bring this drug to patients."

References:

[1] Bristol Myers Squibb Announces Data from EXPLORER-LTE Demonstrating Sustained Improvements in Clinically Meaningful Cardiovascular Outcomes at Weeks 48 and 84 in Patients with Symptomatic Obstructive Hypertrophic Cardiomyopathy Receiving Mavacamten. Retrieved April 4, 2022, from https://investors.bms.com/iframes/press-releases/press-release-details/2022/Bristol-Myers-Squibb-Announces-Data-from-EXPLORER-LTE-Demonstrating-Sustained-Improvements-in-Clinically-Meaningful-Cardiovascular-Outcomes-at-Weeks-48-and-84-in-Patients-with-Symptomatic-Obstructive-Hypertrophic-Cardiomyopathy-Receiving-Mavacamten/default.aspx

[2] Mavacamten Demonstrated Significant Reduction in Need for Septal Reduction Therapy in Symptomatic Obstructive HCM Patients in Phase 3 VALOR Trial. Retrieved April 4, 2022, from https://investors.bms.com/iframes/press-releases/press-release-details/2022/Mavacamten-Demonstrated-Significant-Reduction-in-Need-for-Septal-Reduction-Therapy-in-Symptomatic-Obstructive-HCM-Patients-in-Phase-3-VALOR-Trial/default.aspx

Original Title:Express | Potential "first-in-class" therapy shows latest results, could become a blockbuster

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