Mavacamten works by directly quieting the overactive heart muscle proteins that cause problems in hypertrophic cardiomyopathy (HCM). It’s the first drug designed to target the root cause of this condition rather than just managing symptoms. Sold under the brand name Camzyos, it reduces the excessive squeezing force that thickens the heart wall and blocks blood flow out of the heart.
What Happens Inside the Heart Muscle
Your heart contracts when two proteins, actin and myosin, grab onto each other and pull. In HCM, too many myosin molecules are in an active, “ready to grab” state at any given moment. This creates excessive contractile force, thickens the heart wall over time, and often pushes tissue into the path of blood leaving the heart, creating a pressure obstruction.
Mavacamten targets cardiac myosin directly. It locks myosin molecules into a resting, energy-conserving state called the “superrelaxed state,” where they temporarily stop engaging with actin. Research published in PNAS showed that mavacamten stabilizes a specific configuration where the two heads of the myosin molecule fold back against each other, essentially parking themselves. In this parked position, myosin burns far less energy and can’t generate force. The drug also slows several steps in the chemical cycle that powers contraction, including the release of phosphate and the lever-arm rotation that produces the actual pulling motion.
The net effect is fewer cross-bridges forming between actin and myosin at any given moment. The heart still contracts, but with less excessive force. This is fundamentally different from older treatments like beta-blockers, which slow the heart rate or reduce how hard the entire heart squeezes. Mavacamten selectively dials down the molecular overactivity that defines HCM.
How It Reduces Obstruction
In about two-thirds of people with HCM, the thickened heart muscle partially blocks the left ventricular outflow tract (LVOT), the channel blood passes through on its way to the body. Doctors measure this obstruction as a pressure gradient. Healthy hearts have minimal gradient; obstructive HCM can push it above 30 mm Hg at rest and much higher during exertion.
Mavacamten substantially lowers these gradients. In clinical data, resting LVOT gradients dropped from a median of 65 mm Hg to 12 mm Hg, and provoked gradients (measured during physical stress) fell from 105 mm Hg to 52.5 mm Hg. These reductions persisted over time. At 48 weeks in the long-term extension study, resting gradients were down an average of about 36 mm Hg from baseline, and at 84 weeks the reduction held steady around 33 mm Hg.
Beyond the obstruction itself, mavacamten lowers markers of heart wall stress. Levels of NT-proBNP, a protein the heart releases when it’s under strain, dropped significantly. So did cardiac troponin, a marker of ongoing microscopic damage to heart muscle cells. These biomarker changes suggest the drug isn’t just improving blood flow mechanics but is also reducing the underlying stress on the heart.
What Patients Experience
The landmark EXPLORER-HCM trial tested mavacamten against placebo over 30 weeks in people with symptomatic obstructive HCM. The primary endpoint combined two measures: improvement in exercise capacity (measured by oxygen consumption during peak exercise) along with improvement in functional class, a clinical scale that grades how much daily activity is limited by symptoms like breathness and fatigue.
Among patients taking mavacamten, 37% met this composite endpoint compared to 17% on placebo. In practical terms, people could exercise more and felt less limited in their daily lives. Many moved from being symptomatic with moderate activity to having few or no symptoms during normal tasks. These improvements reflect the reduced obstruction and lower cardiac workload the drug produces at the molecular level.
Dosing and How It Builds Up
Mavacamten is taken as a single daily capsule, with or without food. The typical starting dose is 5 mg, though some patients begin at 2.5 mg depending on other medications they take. The maximum dose is 15 mg per day.
One important characteristic: the drug takes weeks to reach steady-state levels in your blood. Because of this slow buildup, dose adjustments happen gradually. Doctors titrate the dose based on repeated measurements of how well the heart is pumping and how much obstruction remains, aiming to lower the LVOT gradient while keeping the heart’s overall pumping strength in a safe range.
Your body breaks down mavacamten primarily through a liver enzyme called CYP2C19, and people vary genetically in how active this enzyme is. If you’re a slow metabolizer, the drug clears more slowly, blood levels run higher, and your starting dose will be lower (2.5 mg instead of 5 mg). Some patients undergo genetic testing before starting treatment to guide this decision.
Why Close Monitoring Is Required
Because mavacamten reduces how forcefully the heart contracts, taking too much can tip the balance from helpful reduction to dangerous weakening. The heart’s ejection fraction (the percentage of blood pumped out with each beat) needs to stay at or above 50%. If it drops below that, treatment is paused.
This is why mavacamten is only available through a restricted program. Patients need echocardiograms before starting treatment and at regular intervals throughout. These imaging checks track both the ejection fraction and the remaining LVOT gradient, allowing dose adjustments in either direction. Treatment shouldn’t be initiated if the ejection fraction is already below 55%, since there’s less margin for any further reduction.
Drug Interactions That Matter
Several common medications can dangerously raise or lower mavacamten levels in the blood by interfering with the liver enzymes that process it. Strong inhibitors of CYP3A4 or moderate-to-strong inhibitors of CYP2C19 slow the drug’s breakdown, potentially pushing levels high enough to cause heart failure from excessive suppression of contractility. These inhibitors are contraindicated.
The reverse is also a problem. Medications that speed up those same enzymes (moderate-to-strong inducers of CYP2C19 or CYP3A4) can clear mavacamten too quickly, making it ineffective. These are also contraindicated. Even weaker interacting drugs require extra echocardiogram checks after they’re started and a pause on any dose increases for 12 weeks. This is one of the reasons treatment requires careful coordination between the prescribing cardiologist and any other providers managing your medications.
How It Compares to Surgery
Before mavacamten, the main options for obstructive HCM that didn’t respond to beta-blockers or calcium channel blockers were surgical myectomy (physically removing a strip of thickened heart muscle) or alcohol septal ablation (injecting alcohol to shrink the obstructing tissue). Both are effective but invasive, carry procedural risks, and require recovery time.
Mavacamten offers a nonsurgical alternative that addresses the same obstruction through a different path. Rather than removing tissue, it reduces the force that makes the remaining tissue problematic. For many patients, this eliminates or delays the need for an invasive procedure. It does, however, require indefinite daily use and ongoing monitoring, which surgery does not.