ESC: MyoKardia’s mavacamten boosts heart function in phase 3, teeing up 2021 filing

ESC: MyoKardia’s mavacamten boosts heart function in phase 3, teeing up 2021 filing

Earlier this year, MyoKardia presented preliminary data showing its long-awaited targeted heart therapy mavacamten could move the needle on certain cardiac protein biomarkers linked to signs of heart stress and injury.

Now, a phase 3 pivotal trial has demonstrated that the first-in-class drug can perform as a disease-specific therapy for hypertrophic cardiomyopathy, or HCM, by preventing the thickened heart muscle associated with the disease from obstructing the flow of blood.

In the latest study—dubbed Explorer-HCM, one of the largest in the disease—the once-daily drug showed statistically significant improvements in heart function and oxygen consumption after 30 weeks, with 36.6% of treated patients meeting that mark, compared with 17.2% of those who received a placebo.

Patients treated with mavacamten also reported that they could exercise more and generally felt better, with improvements in shortness of breath and other quality of life scores.

“Every aspect of objective performance and subjective well-being improved on the treatment,” Iacopo Olivotto, the study’s lead clinical investigator, said in a press conference during the European Society of Cardiology’s virtual annual meeting, where the data were unveiled. At the same time, mavacamten was generally well tolerated, with similar rates of serious side effects.

MyoKardia said the Explorer-HCM data will form the basis of its submission to the FDA, slated for the first quarter of next year. The study’s results were also published in The Lancet.

In March, at the annual meeting of the American College of Cardiology, the company presented phase 2 data showing mavacamten could significantly reduce blood levels of cardiac troponin I and N-terminal pro-brain natriuretic peptide, or NT-proBNP—two proteins that signal the muscles of the heart wall are under damaging stress—among patients with non-obstructive HCM. Similar reductions were seen in the Explorer study. MyoKardia plans to pursue additional studies in the separate non-obstructive indication in the future, along with supplementary FDA filings.

Thickening of the heart muscle and obstructions can lead to chest pain, palpitations, fatigue, lightheadedness or fainting, though some people may show no symptoms at all. Left untreated, the condition can progress into heart failure, and require interventions such as ablation or open surgery.

Mavacamten acts as a myosin inhibitor, disengaging a number of the cellular motors within the heart’s muscle tissue that drive contractions. By tailoring the amount of drug given, MyoKardia aims to apply a molecular brake on the strength of each heartbeat—enough to reduce the excessive forces that may constrict certain valves, but not too much that the heart can’t pump blood out to the body. This also makes it easier for the heart to relax and refill with blood, and beat more efficiently.

“Mavacamten is the first therapeutic candidate to target the heart muscle proteins that drive the excessive contractility and impaired relaxation that are hallmarks of HCM with the intent of correcting the abnormal function of the heart,” Daniel Jacoby, a study investigator and director of the heart failure program at the Yale School of Medicine, said in a statement.

Whether mavacamten can spare patients from surgical procedures, though, remains to be seen. That question will be tackled in a separate trial, Valor-HCM, which began dosing its first patient earlier this month. The company estimates that 1,500 people annually in the U.S. undergo surgery to relieve obstructions of the heart’s left ventricle.

But to the drug’s credit, the majority of the patients in the Explorer study did not qualify for surgery or have an immediate need, illustrating the ability of mavacamten to offer an earlier and broader therapy option to HCM patients, Olivotto said.

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