Extension Study Shows Efficacy and Safety of Mavacamten in the Treatment of Hypertrophic Cardiomyopathy

The use of mavacamten, a new cardiac myosin inhibitor, to treat people with symptomatic hypertrophic obstructive cardiomyopathy (HCM), a condition that causes excessive thickening of the heart muscle, has shown continued benefits in quality of life and patient outcomes over an extended period of time, according to interim data from the EXPLORER-HCM extension study presented at the American College of Cardiology’s 71st Annual scientific session. Specifically, researchers reported that mavacamten was associated with significant and long-lasting improvements in left ventricular outflow tract (LVOT) gradients, which is the degree of obstruction, health status, symptoms at the stress and a key blood marker of heart failure.

“These data are very consistent with initial trial results: cardiac obstruction was relieved, two-thirds of patients felt better, and disease severity improved,” said Florian Rader, MD. , co-director of the Cedars Sinai Hypertrophic Cardiology Clinic and the study’s senior author, adding that this is the largest and longest-running report on mavacamten treatment in obstructive HCM. “The thickening caused by HCM can obstruct blood flow out of the heart, leading to distressing symptoms and poor quality of life for many patients. Based on these findings, the drug does not lose effectiveness with the time and appears to be safe and well tolerated over the long term.”

MAVA-LTE is an ongoing five-year, dose-blinded extension study that includes 231 of 244 patients who completed treatment in the Phase 3 EXPLORER-HCM trial. EXPLORER-HCM results showed significant improvements in patient health status, symptoms, exercise capacity and quality of life among those taking mavacamten compared to placebo after 30 weeks. The MAVA-LTE study was designed to collect longer term data. At the time of data closure for this analysis, patients were on average 60 years old and 39% were female.

Patients were initially given 5 mg of mavacamten once a day after stopping the drug (called the washout period). Patients could eventually take 2.5, 5, 10, or 15 mg, with dose adjustments at weeks four, eight, and 12 and again at 24 weeks based on echocardiograms read at the local site, which examined the degree of gradient obstruction and checked normal ejection fraction (>50%). If the gradient was greater than 30 mmHg, patients were eligible to increase the dose to further reduce the gradient and obstruction. If patients showed signs of reduced left ventricular ejection fraction (

The median follow-up was 62 weeks and ranged from one to 124 weeks, meaning that not all patients took mavacamten at the designated follow-up of 48 or 84 weeks, which are reported in this interim analysis. In patients assessed at these time points, 206 at 48 weeks and 66 at 84 weeks, the degree of obstruction measured by the LVOT gradient was lowered by an average of 36 mmHg at 48 weeks (a 74% reduction compared to inclusion) ; this reduction was maintained through week 84. At week 84, 83.5% of patients followed at that time had LVOT gradients below 30 mmHg, which is considered the threshold for obstruction of the blood flow out of the heart.

In terms of NYHA class, 68% of patients improved by at least one class designation, with the most dramatic change in Class I, meaning no significant exertional symptoms. At baseline, only 6% of patients were in class I, but this increased to 55% of patients at week 48. In contrast, 29% of patients were in class III, showing a noticeable limitation in physical activity at week 48. start of the study. ; the proportion of people in this class drops to 4.9% at 48 weeks. At baseline, almost everyone (94% of patients) had some degree of shortness of breath on exercise; at 48 weeks, only 45% of patients reported feeling this way. Additionally, the heart failure marker NTproBNP decreased by 480 ng/L at week 48 and 488 ng/L at week 84, a reduction of 63%. NTproBNP is released by the heart in the event of elevated cardiac pressure (i.e., heart failure); Rader said large changes in this marker indicate significant improvement in heart failure in these patients.

Mavacamten was well tolerated and there were no new or unexpected adverse events reported, Rader said. Thirty-four (14.7%) patients reported a serious adverse event, but Rader said only a few of these were considered mavacamten-related. Twenty-six patients had to temporarily stop treatment, 12 of them because their ejection fraction was lower than normal. Twenty patients restarted myvacamten, including eight who had ejection fraction. There were three deaths during the study period – one from cardiac arrest, one from heart infection and one from heart attack, all of which were deemed unrelated to mavacamten.

Medication options for HCM are limited, and many patients require surgical removal of part of the thickened heart muscle or alcohol septal ablation to reduce the obstruction. While these invasive treatment options are effective, they also come with risks. Mavacamten is the first drug specifically designed to relieve this obstruction and, as the data shows, it helps patients feel better and lead more active lives. If this drug continues to be effective over time, it may also help patients avoid having to undergo an invasive procedure or open-heart surgery to relieve the obstruction.”

Florian Rader, MD, co-director of the Cedars Sinai Hypertrophic Cardiology Clinic and lead study author

HCM is the most common genetic heart disease. It is estimated to affect 1 in 500 adults, but many patients go undiagnosed. Changes in certain genes allow the heart muscle to become too thick (“hypertrophy” means to thicken). In some cases, the left ventricular outflow tract (LVOT), where blood leaves the heart, becomes blocked by thickened heart muscle, forcing the heart to work harder and preventing people from performing even simple tasks without straining. feeling short of breath and tired. Obstructive HCM is also associated with increased risks of atrial fibrillation, stroke, heart failure and, although rare, sudden cardiac death.

Mavacamten is currently under review by the United States Food and Drug Administration for use in obstructive HCM, with a decision expected in late April 2022.

The study was funded by MyoKardia, a wholly owned subsidiary of Bristol Myers Squib.

For more information on HCM, visit www.CardioSmart.org/HCM.

Rader will be available to the media at a press conference on Sunday, April 3 at 11:15 a.m. ET / 3:15 p.m. UTC in room 103AB.

Rader will present the study, “Cumulative Results Update of Treatment with Mavacamten from the EXPLORER-LTE Cohort of the MAVA-LTE Study in Patients with Hypertrophic Obstructive Cardiomyopathy,” on Sunday, April 3 at 9:45 a.m. ET / 1:45 p.m. UTC in the Great Tent, Hall D.


American College of Cardiology

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