Bristol Myers Squibb ponied up $13 billion for MyoKardia last fall, just months after it showed its targeted drug could prevent thickened heart muscle from blocking blood flow in patients with an inherited heart disorder. Now, the Big Pharma is unveiling more data from that phase 3 study, highlighting the drug’s effect on patients’ symptoms and quality of life.
Dubbed Explorer-HCM, the study pitted the drug, mavacamten, against placebo in 251 patients with obstructive hypertrophic cardiomyopathy. Also called HCM, the inherited disorder causes the muscle walls of the heart to thicken, potentially to the point where they can obstruct blood flow.
After 30 weeks, the drug, mavacamten, beat placebo at improving patients’ scores from baseline on the Kansas City Cardiomyopathy Questionnaire (KCCQ), a measure of how patients perceive their health status, including their heart failure symptoms and how they affect their quality of life, and physical and social function.
The analysis also found that more than twice as many patients on mavacamten than placebo logged an improvement of more than 20 points on the questionnaire (36% versus 15%), a change that Jay Edelberg, M.D., Ph.D., head of heart failure and cardiomyopathy development at Bristol Myers, called “transformative.”
The new analysis was presented virtually on Saturday at the annual meeting of the American College of Cardiology.
The KCCQ is an important tool for cardiologists caring for patients with HCM, who may experience their own unique symptoms, said Edelberg, who was previously the chief medical officer at MyoKardia.
Thickening of the heart muscle and obstructions can lead to chest pain, palpitations, fatigue, lightheadedness or fainting, though some people may not show symptoms at all. Left untreated, patients can develop heart failure and require interventions such as ablation or open surgery.
“The KCCQ is important, of course, for showing how they are doing in their day-to-day management,” Edelberg said. But that’s not all: “It’s not just an element of feeling better, but actually, it is a prognostic indicator. An improvement of five points is considered clinically meaningful.”
Unlike other HCM treatments, which focus on managing symptoms, mavacamten is designed to tackle the condition at its source. It inhibits myosin to reduce the excess number of cellular motors that engage with each heartbeat, thereby cutting the strength of each contraction of the ventricle. This way, the person’s pulse rate can stay the same while the heart has an easier time pumping and refilling with blood.
“What we’ve seen with mavacamten is that so many of our patients have really improved their symptoms,” Edelberg said. “They’ve improved their ability to exercise, and we’ve seen almost 30% of our patients become asymptomatic after just 30 weeks.”
Last August, MyoKardia presented data from the study showing the drug beat placebo at improving patients’ heart function and oxygen consumption after 30 weeks. Two-thirds of the mavacamten patients hit that mark compared with 17.2% of patients who received placebo. Those data teed up an FDA submission for mavacamten, which the agency accepted in March. It expects to decide the drug’s fate by Jan. 28, 2022.
As Bristol Myers starts working with regulators to win approvals for mavacamten in obstructive HCM, it will continue developing the drug for other types of heart disease, including non-obstructive HCM and heart failure with preserved ejection fraction (HFpEF), a type of heart failure which the organ pumps normally, but its tissue is too stiff to fill properly. The company is also testing whether the drug can spare patients from surgical procedures.