According to William Jenkins, a consultant cardiologist at the Royal Infirmary of Edinburgh, real-world results with mavacamten mirror the positive outcomes seen in clinical trials such as EXPLORER and VALOR-HCM.

High Symptom Enhancement Rates

Data from three UK centers indicated that 70% to 80% of patients experienced noticeable symptomatic improvement with mavacamten therapy, as shown in a study published in Open Heart. Furthermore, 90% of patients experienced a 30 mm Hg reduction in the left ventricular outflow tract (LVOT) gradient, wich is considered a significant decrease in obstruction.

“HCM is something that develops over decades…You can develop symptoms early, but you can have those symptoms for a really long time.”

While “very intense echocardiographic surveillance” was initially necessary, Jenkins noted that the process “gets much easier” following the first few months of treatment.

He told Medscape News UK that, “I think our reliance upon echocardiography will probably reduce as we get more experience with this.”

Novel Therapeutic Approach

Mavacamten, a first-in-class cardiac myosin inhibitor, functions by normalizing contractility, alleviating dynamic LVOT obstruction, and enhancing cardiac filling pressures in individuals with HCM.

“HCM is something that develops over decades,” Jenkins explained.”You can develop symptoms early, but you can have those symptoms for a really long time before you go on to develop other things like abnormal heart rhythms, heart failureor dying suddenly.”

He also suggested that many patients could benefit from treatment, even though oHCM is considered uncommon.

Jenkins also pointed out that the management of HCM sometimes falls under general cardiology in certain facilities,which raises concerns that patients might not receive the necessary frequent monitoring.

“People live with it for years and years – if not decades – before they develop any of the end stage features of HCM,” Jenkins stated. “they can become very adapted to their symptoms.”

Patient Perspectives

Hypertrophic cardiomyopathy affects approximately 1 in 500 individuals in both the UK and the US, with about two-thirds of these cases involving obstruction.

Katharine McIntosh,head of research and policy at Cardiomyopathy UK,told Medscape News UK that mavacamten had generated considerable “excitement” among patients,calling it “the first big cardiomyopathy-specific drug.”

McIntosh voiced her dissatisfaction with the drug’s gradual implementation, noting that it was approved for use by the National Health Service in England and Wales in 2023 and in scotland in 2024.

“It’s at the point now where one would have thought that everyone who should be on it would be getting onto it. but that’s just not been the case,” she said.

According to a recent survey by Cardiomyopathy UK, patients who had access to mavacamten had “very positive” experiences with the medication. McIntosh reported that respondents described it as “life changing” and felt as though they had been given a second chance at life.

Barriers to Wider Adoption

One obstacle is that onyl specialists with expertise in treating cardiomyopathies can prescribe and monitor mavacamten,which limits its availability in all centers.

According to prescribing guidelines, patients must undergo echocardiography both before starting treatment and at regular intervals thereafter. To determine appropriate dosage, genetic testing for Cytochrome P450 (CYP) 2C19 (CYP2C19) is also necessary.

Future Directions

Jenkins outlined three critical considerations for prescribing mavacamten:

• Close monitoring is essential in the early stages, as the drug has the potential to cause left ventricular systolic dysfunction.
• Pharmacy input is required due to CYP2C19-related drug interactions.
• Counseling is vital because of potential risks to the fetus.

“Most people tolerate this [drug] very well,” he stated. After the first 12 weeks,follow-up visits can be reduced to every three to six months.

“This is an indefinite medication for a lot of people,” Jenkins commented. However, given the estimated annual cost of nearly £14,000 per patient, he emphasized the importance of careful initial use.

“Right now,the indication is for symptomatic,severe LVOT obstruction,” he said. Though, “there’s no reason in the long-term why this shouldn’t become first-line.”

It is still uncertain whether mavacamten is beneficial for HCM patients who do not have obstruction.