Targeted cardiomyopathy drug, Camzyos effective in Asians

Milind Y. Desai, a professor of Department of Cardiovascular Medicine at Cleveland Clinic, USA

Camzyos, a myosin inhibitor, emerges as the first targeted treatment for HCM

In a global clinical trial, Camzyos treatment brings half of patients to asymptomatic levels.

EXPLORER-CN, enrolling Chinese patients, results were consistent with those observed in global studies

Milind Y.

 

Desai, a professor of Department of Cardiovascular Medicine at Cleveland Clinic, US

The first targeted treatment option for obstructive hypertrophic cardiomyopathy has finally emerged.

 

Obstructive hypertrophic cardiomyopathy (oHCM) is a sub-classification of hypertrophic cardiomyopathy that is characterized by LV outflow tract (LVOT) obstruction impeding blood flow from the heart to the rest of the body.

 

Previously, the treatment options for HCM were limited to chronic disease treatments such as beta-blockers and calcium channel blockers.

 

While these drugs could indirectly manage HCM symptoms, if there was no improvement, there were no other treatment options besides surgery.

 

In this context, BMS’s development of Camzyos offered a targeted therapy option for HCM.

 

Camzyos differs from existing drugs as it directly inhibits myosin, leading to improvements in symptoms and exercise capacity in patients.

 

Camzyos functions by reducing the number of actin-myosin cross-bridges that constricts cardiac muscle, thus relaxing the cardiac muscle.

 

In clinical trials, once-daily administered Camzyos showed significant improvement, bringing about half of the patients to asymptomatic levels.

 

Additionally, 74% of patients experienced considerable improvement in obstructed left ventricular outflow, to the point where they no longer required consideration for Septal Reduction Therapy (SRT).

 

Based on such clinical results, Camzyos was approved in May in Korea, becoming the first drug in Asia to be approved to enhance exercise capacity and alleviate symptoms in adult patients with symptomatic oHCM.

 

Milind Y.

 

Desai, a professor of Department of Cardiovascular Medicine at Cleveland Clinic in the US, analyzed that the demand for Camzyos will rise in medical settings based on results of the studies on Asian patients, as they have shown results consistent to those observed in global clinical studies.

 

Q.

 

What is the current global prevalence of HCM? The estimated global prevalence of HCM is about 1 in 500 or 1 in 200 people.

 

Considering these figures, millions of people worldwide should be diagnosed with HCM; however, approximately 85% of these cases go undetected due to misdiagnosis, underdiagnosis, or delayed diagnosis.

 

Based on a prevalence rate of 1 in 500, in the US with a population of approximately 340 million, it's estimated that there should be about 700,000 people diagnosed with HCM.

 

However, the current number of diagnosed patients is estimated to be only about 100,000 to 120,000.

 

This suggests a substantial disparity between the actual prevalence of the condition and the number of diagnosed cases.

 

Q.

 

What is the treatment strategy for HCM? Until recently, the treatment strategy for HCM primarily concentrated on alleviating symptoms.

 

With no medications specifically approved for HCM, drugs for coronary artery disease, such as beta-blockers, calcium channel blockers, and disopyramide, were used for treating HCM.

 

If symptoms failed to improve with these medications, patients had only invasive treatments, such as surgery, as alternatives.

 

Unlike any existing treatments, Camzyos is the first therapy to directly target the underlying pathophysiology of HCM.

 

Camzyos can inhibit excessive actin-myosin cross-bridges in cardiac muscle.

 

By allowing only the necessary amount of actin-myosin binding to occur, it normalizes the excessive cardiac contractions, effectively treating the obstructed cardiac structure and its related symptoms.

 

Q.

 

In clinical trials, symptoms and exercise capacity of the patients who received Camzyos were significantly improved.

 

In the EXPLORER-HCM trial, patients who received Camzyos achieved both primary and secondary endpoints with significant improvements over those who received placebo.

 

A higher percentage of Camzyos-treated patients achieved each of the composite functional end point (an improvement of at least 1.5 mL/kg/min in peak oxygen consumption (VO2) accompanied by an improvement from baseline of at least one NYHA functional class, an improvement from baseline of 3.0 mL/kg/min or greater in peak VO2 maintaining NYHA functional class) compared with the placebo group.

 

Patients treated with Camzyos showed a higher proportion of relieved LVOT pressure gradients towards normal levels and enhanced quality of life compared to the placebo group.

 

Overall, Camzyos showed significant improvements across all evaluated parameters when compared to the placebo, thereby confirming its superiority in terms of both safety and efficacy.

 

In addition to sustained effectiveness observed in clinical trials, patients treated with Camzyos showed reduced hypertrophied cardiac muscle thickness and size to optimal levels and were resolved of issues with stiff cardiac muscles.

 

Furthermore, in a separate clinical study, EXPLORER-CN which had been conducted in Chinese patients, the results were consistent with those observed in global studies, despite the fact that these patients started treatment at lower doses, confirming Camzyos is an effective treatment option for Asian patients.

 

Q.

 

If you have experience prescribing Camzyos, what actual treatment outcomes have observed with its use?

 

How has it impacted patients’ prognosis and satisfaction with the treatment? Currently, approximately 7,000 patients across the US are receiving treatment with Camzyos.

 

The real-world data indicates a discontinuation rate of Camzyos therapy at around 2.2%, which is lower than what was reported in clinical trials.

 

Among the patients receiving Camzyos treatment at the Cleveland Clinic, there were no cases requiring myectomy, and even patients who had previously undergone myectomy at other medical institutions without symptom improvement have shown a positive prognosis after starting Camzyos treatment at the Cleveland Clinic.

 

Q.

 

In August, the European Society of Cardiology (ESC) updated its HCM guideline.

 

What are the most noteworthy changes? In the past, HCM guidelines had to rely on limited evidence, such as small-scale observational data from individual institutions, retrospective analysis, or consensus opinions from experts.

 

For the past nine years since 2014, there were no drugs that has produced enough data to justify updating the guidelines.

 

During this period, no drugs have received a recommendation with a level of evidence higher than B.

 

However, Camzyos has completely changed the circumstances.

 

With significant efficacy demonstrated in two large-scale Phase 3 randomized controlled trials (RCT), Camzyos has received a recommendation of A based on the newly revised ESC guidelines, making it the first treatment option to receive the highest level of evidence.

 

Nevertheless, there was some surprise and disappointment as Camzyos had hoped to receive a Class 1 recommendation but was instead granted a Class 2A recommendation.

 

Currently, the American College of Cardiology (ACC) and the American Heart Association (AHA) are also preparing for guideline updates, with new announcements expected early next year.

 

Q.

 

In conclusion, how do you predict the paradigm of the HCM treatment will shift in the future? The first step would be assessing the patients diagnosed with HCM for the presence of symptoms.

 

If symptoms are present, treatment could begin with first-line treatment options such as beta-blockers, calcium channel blockers, or disopyramide.

 

If initial drugs fail to alleviate symptoms in HCM patients, it may be more effective to consider transitioning to Camzyos at an appropriate time, rather than simply increasing the dosage and continuing the treatment.

 

However, it's important to know that treating HCM isn't a linear progression from beta-blockers to Camzyos, and then to surgery.

 

Treatment should be tailored to the patient's specific condition, which might necessitate moving back and forth between these stages.

 

The precision medicine approach is already applied in the field of HCM, with AI-based diagnostic tools identifying more patients, and therapies targeting specific genetic mutations are under exploration.

 

Considering these advancements, the future of HCM treatment is expected to become more diverse, offering therapeutic options that are more appropriately tailored to each patient's circumstances.