What Is Mavacamten?
Mavacamten is an FDA-approved medication for obstructive hypertrophic cardiomyopathy (oHCM). It is also known by its brand name, Camzyos. This medication works as a selective cardiac myosin inhibitor. This means it helps to reduce the excessive contraction of the heart muscle, which is a key problem in hypertrophic cardiomyopathy.
In patients with oHCM, mavacamten aims to improve symptoms and functional capacity by addressing the underlying issue of hypercontractility. Beyond its approved use, mavacamten is also being investigated for its effects on myocardial blood flow in patients with oHCM, as well as for other forms of hypertrophic cardiomyopathy.
Uses and Conditions Under Study
Mavacamten is primarily studied for various forms of hypertrophic cardiomyopathy (HCM), a condition where the heart muscle becomes abnormally thick, making it harder for the heart to pump blood. The drug's mechanism of reducing excessive heart muscle contraction is particularly relevant for these conditions.
- Obstructive Hypertrophic Cardiomyopathy (oHCM): This is the most studied condition, with a total of 15 trials specifically focusing on obstructive hypertrophic cardiomyopathy, oHCM, or hypertrophic obstructive cardiomyopathy (HOCM). In oHCM, the thickened heart muscle blocks blood flow from the heart to the body. Mavacamten is prescribed as part of routine care for symptomatic HOCM, with studies evaluating its effect on myocardial perfusion over a 12-month period.
- Hypertrophic Cardiomyopathy (HCM): A broader category of HCM, including unspecified forms, is being investigated in 12 trials. Mavacamten is studied as an addition to guideline-directed standard medical therapy for patients with HCM, including those with mid-to-apical left ventricular obstruction.
- Non-obstructive Hypertrophic Cardiomyopathy: Mavacamten is also being studied in 2 trials for non-obstructive hypertrophic cardiomyopathy, where the thickened heart muscle does not block blood flow but can still cause symptoms.
- Healthy Participants and Pharmacokinetic Studies: A total of 6 trials involve healthy participants or focus on the drug itself (listed as "Mavacamten" trials). These studies help researchers understand how the drug is absorbed, distributed, metabolized, and eliminated by the body, as well as its safety profile.
- Combination Therapy: One trial is exploring mavacamten combined with radiofrequency ablation, a procedure sometimes used to treat HCM, to see if the combination offers additional benefits.
Dosing
Mavacamten, also known by its brand name Camzyos, is typically taken orally. Clinical trials have investigated various dosing strategies and strengths to determine the most effective and safest treatment regimens.
Studies have explored different doses, including specific strengths such as 15 mg and 25 mg. Other trials refer to "Mavacamten Dose 1," "Mavacamten Dose 2," or "Mavacamten- Dose A" and "Mavacamten- Dose B," indicating that a range of strengths are under investigation to optimize treatment for patients with hypertrophic cardiomyopathy. Dosing regimens often involve a "specified dose on specified days" according to trial protocols.
Some studies also investigate how mavacamten interacts with other substances. For example, specific cohorts have studied mavacamten in combination with activated charcoal with sorbitol, which can affect drug absorption. Additionally, mavacamten has been studied as monotherapy and in combination with procedures like radiofrequency ablation.
Side Effects
The most common side effect reported in patients taking Mavacamten was dizziness, experienced by 17.4% of patients, compared to 10.0% of those on placebo. Other common side effects observed in clinical trials included:
- Dyspnoea (shortness of breath): 12.0% of patients taking Mavacamten experienced this, compared to 9.4% on placebo.
- Upper respiratory tract infection: 11.3% of patients on Mavacamten, compared to 4.4% on placebo.
- Fatigue: 11.3% of patients on Mavacamten, compared to 5.9% on placebo.
- Palpitations: 9.9% of patients on Mavacamten, compared to 7.4% on placebo.
- Headache: 9.1% of patients on Mavacamten, compared to 7.9% on placebo.
- Constipation: 9.1% of patients on Mavacamten, compared to 2.7% on placebo.
- Atrial fibrillation: 9.1% of patients on Mavacamten, compared to 0.0% on placebo.
In some trials, nasopharyngitis (common cold) was reported in 11.4% of patients taking Mavacamten, which was less frequent than the 14.3% reported in patients taking placebo.
Clinical Trial Results
Clinical trials have evaluated Mavacamten for Hypertrophic Cardiomyopathy (HCM) and Heart Failure with Preserved Ejection Fraction (HFpEF).
Obstructive Hypertrophic Cardiomyopathy (oHCM)
In a study (NCT03470545) of adults with symptomatic obstructive HCM, Mavacamten showed significant improvements in heart-related quality of life and symptoms. Patients treated with Mavacamten experienced an average improvement of 13.6 points in their Kansas City Cardiomyopathy Questionnaire (KCCQ) score, compared to a 4.2-point improvement with placebo. Mavacamten also reduced the severity of HCM symptoms by an average of 2.8 points, versus 0.9 points with placebo. Additionally, Mavacamten led to an average increase of 1.4 mL/kg/min in peak oxygen consumption (pVO2), while placebo showed a slight decrease of 0.05 mL/kg/min. The drug also significantly reduced the post-exercise left ventricular outflow tract (LVOT) peak gradient by 47 mmHg, compared to a 10 mmHg reduction with placebo.
Another study (NCT04349072) focused on obstructive HCM patients eligible for septal reduction therapy (SRT). At Week 16, only 17.9% (10 out of 56) of patients on Mavacamten were still considered eligible for SRT or decided to proceed with it, compared to 76.8% (43 out of 56) of patients who initially received placebo and then switched to Mavacamten. This indicates Mavacamten significantly reduced the need for SRT. Furthermore, 62.5% (35 out of 56) of Mavacamten-treated patients saw at least a one-class improvement in their New York Heart Association (NYHA) functional class, compared to 21.4% (12 out of 56) in the placebo group. Mavacamten also improved the KCCQ score by an average of 10.4 points and reduced the post-exercise LVOT gradient by 39.1 mmHg, compared to smaller changes in the placebo group.
In a long-term extension study (NCT03496168), Mavacamten continued to show benefits. Patients experienced an average reduction in NT-proBNP levels (a marker of heart strain) of approximately 1500 ng/L over time, and sustained improvements in KCCQ scores, averaging around 17-18 points. Up to 91.7% of participants showed at least a one-class improvement in their NYHA functional class at various time points during the study. Serious adverse events like seizures, sudden death, cardiovascular death, myocardial infarction, and strokes were not reported in any participants in this extension study.
Non-Obstructive Hypertrophic Cardiomyopathy (nHCM)
A Phase 2 study (NCT03442764) in adults with symptomatic Non-Obstructive Hypertrophic Cardiomyopathy evaluated safety outcomes. The percentage of participants who experienced at least one serious treatment-emergent adverse event was 11.1% in one Mavacamten group and 9.5% in another, compared to 21.1% in the placebo group. The percentage of participants who experienced at least one treatment-emergent adverse event was 88.9% and 90.5% in the Mavacamten groups, respectively, compared to 68.4% in the placebo group.
Heart Failure with Preserved Ejection Fraction (HFpEF)
In a study (NCT04766892) of participants with Heart Failure with Preserved Ejection Fraction, Mavacamten treatment resulted in a reduction in cardiac biomarkers. At Week 26, resting high-sensitivity cardiac troponin T (Hs-cTnT) levels were reduced to 0.8645 times baseline levels, and resting NT-proBNP levels were reduced to 0.7354 times baseline levels. A total of 23 participants experienced treatment-emergent adverse events, and 5 participants experienced treatment-emergent serious adverse events.
Currently Recruiting Trials
Mavacamten is currently being investigated in several clinical trials around the world, focusing on its effectiveness and safety for patients with hypertrophic cardiomyopathy (HCM). These studies aim to gather more real-world data and understand specific aspects of the medication. One significant study, NCT05489705, is a prospective registry evaluating patient characteristics, treatment patterns, and long-term outcomes for symptomatic obstructive HCM in the United States and Europe. This large study aims to enroll 1600 participants. Similarly, several observational studies are assessing the real-world effectiveness and safety of mavacamten in specific regions. These include , a post-marketing surveillance study in Korea targeting 600 participants. Another post-marketing surveillance study, , is evaluating the safety, tolerability, and effectiveness of mavacamten in 50 adults with symptomatic obstructive HCM. Beyond regional effectiveness, other trials delve into specific physiological impacts or patient experiences. , also with 20 participants, is exploring myocardial perfusion changes following optimal medical treatment in symptomatic hypertrophic obstructive cardiomyopathy. To understand the patient's perspective, Mavacamten Pregnancy Surveillance Program is collecting data on maternal, fetal, and infant outcomes, aiming for 20 enrollees.Where to Participate
Clinical trials for mavacamten are actively recruiting across a wide geographic area, offering opportunities for patients in various locations to participate. These studies are open to individuals between 15 and 85 years of age, and all genders are welcome. Healthy volunteers are not eligible for these specific mavacamten trials, but children may be considered depending on the study. Overall, there are 65 sites across 53 cities in 32 states participating in mavacamten research. The top cities with multiple recruiting sites include:- Boston, Massachusetts (3 sites)
- Cleveland, Ohio (2 sites)
- Baltimore, Maryland (2 sites)
- Charlottesville, Virginia (2 sites)
- New York, New York (2 sites)
- Pittsburgh, Pennsylvania (2 sites)
- Indianapolis, Indiana (2 sites)
- Nashville, Tennessee (2 sites)
- Houston, Texas (2 sites)
- Dallas, Texas (2 sites)