Bristol Myer Squibb (BMS)’s Camzyos has emerged as a groundbreaking treatment for obstructive hypertrophic cardiomyopathy (oHCM), a rare disease in which the muscle in the pumping chamber of the heart becomes thickened, an expert said in an interview with Korea Biomedical Review. 

Until now, the only drug options available for treating HCM were beta-blockers and calcium channel blockers, which are typically used for chronic conditions. These drugs managed HCM symptoms indirectly, but when symptoms did not improve, there were no alternatives except for surgery.

Unlike previous drugs, Camzyos directly inhibits cardiac myosin, improving patients' symptoms and exercise capacity. It reduces the number of cross-links between myosin and actin, relaxing the heart muscle.

In clinical trials, Camzyos, taken once daily, showed improvement in symptoms to a level of no symptoms in about half of the patients, with 74 percent of patients experienced such improvement in the obstructed left ventricular outflow tract that they no longer needed to consider Septal Reduction Therapy (SRT).

Based on these clinical results, Camzyos was approved in May in Korea, becoming the first in Asia for the treatment of symptomatic oHCM in adult patients to improve exercise capacity and symptoms.

In an interview with Korea Biomedical Review, Professor Milind Y. Desai from the Cleveland Clinic provided insights into the complexities of HCM and the significance of the development of Camzyos.

Professor Desai is a globally recognized authority on heart disease who participated in the Camzyos clinical trials. Currently, he is active as a reviewer for international academic journals such as The Lancet, The New England Journal of Medicine (NEJM), and the Journal of the American College of Cardiology (JACC).

"HCM is a disease where the heart muscle abnormally thickens without other causes such as hypertension, with the most common cause being genetic predisposition," Desai said. "The global prevalence of HCM is estimated at 1 in 500 or 1 in 200 people, yet about 85 percent of these patients remain undiagnosed or misdiagnosed."

Desai attributed the rising numbers of HCM patients to increased disease awareness and advancements in diagnostic methods and treatments.

"Recently, there has been an increase in awareness about (HCM), leading to a rise in patient numbers in regions like Korea and others,” the professor said. “Specifically, we are now able to meaningfully test symptoms that were previously unnoticed or overlooked, and efforts to actively identify patients who could benefit from new drugs have led to an increase in diagnosis rates.”

According to Desai, HCM can lead to various cardiovascular complications, such as arrhythmias and heart failure, due to abnormalities in heart shape and function.

“About 40 percent of HCM patients are reported to have heart failure, and the risk of developing atrial fibrillation is four to six times higher than in the general population,” he said. “Moreover, HCM can be a fatal disease, where the first symptom could lead to sudden death.”

The mortality rate among HCM patients in their 20s is reported to be more than four times higher than in the general population, and it is also a major cause of sudden cardiac death in athletes under 35, he added.

Despite this, clinical studies evaluating the safety and efficacy of drug treatments for HCM patients have been limited, and until recently, drug treatment for HCM has been confined to symptom relief.

“Until now, HCM treatment focused on symptom relief,” he said. “There were no drugs approved specifically for HCM treatment, so drugs for coronary artery disease were adapted.”

For instance, beta-blockers, calcium channel blockers, and disopyramide were used, but when these drugs failed to improve symptoms, invasive treatments like surgery were the only option, he added.

In contrast, Desai stressed that Camzyos acts directly on the pathophysiological mechanism of HCM, fundamentally improving HCM.

“Unlike previous drugs, Camzyos targets the underlying pathophysiology of HCM, possessing a mechanism that inhibits excessive cross-linking of actin and myosin,” he said. “In other words, by regulating the binding of a proper number of actin and myosin molecules, Camzyos normalizes excessive heart contractions and effectively treats obstructed heart structures and related symptoms.”

The global medical community has also seen a change in the HCM treatment landscape after the introduction of Camzyos.

After its launch, the European Society of Cardiology (ESC) revised its myocardial disease management guidelines in August this year, the first revision in about nine years since 2014.

According to the new guidelines, Camzyos is strongly recommended (Class IIa, Level of Evidence A) as a second-line treatment for symptom improvement in adult myocardial disease patients with obstructed left ventricular outflow.

Camzyos is the only drug recommended at the highest evidence level A in the guidelines.

“Past HCM guidelines were based on small-scale observational data reported by individual institutions, retrospective analysis results, and expert consensus,” Desai said. “In the nine years since 2014, there had been no drug reporting clinical data sufficient to revise the guidelines, and there were no treatment options with evidence level higher than B.”

However, Camzyos, through two major phase 3 clinical trials, confirmed its effectiveness and received the highest evidence level A recommendation in the newly revised ESC guidelines, he added.

Desai went on to add that the American College of Cardiology (ACC) and the American Heart Association (AHA) are also preparing to update their guidelines, with new announcements expected early next year.

“For patients diagnosed with HCM, starting treatment with first-line options like beta-blockers and then transitioning to Camzyos at the right time, rather than just increasing the dosage of drugs, would be more effective,” he said.

During his final remarks, Desai also addressed Korean healthcare providers and patients, noting that with the advent of fundamental treatments, it's now crucial for both patients and medical professionals to improve their awareness as 85 percent of patients still in the blind spot receive timely and appropriate treatment.

“Due to the nature of HCM, patients often do not immediately seek medical attention even when they have symptoms, or they may experience misdiagnosis or diagnostic wandering even when they do visit a hospital,” he said. “Therefore, it is necessary to explain in detail to patients what causes hypertrophic cardiomyopathy and what problems can arise."

Beyond consultations, providing patients with additional materials about hypertrophic cardiomyopathy and its treatments or introducing them to support groups can greatly aid in their treatment, he added.

Desai finally noted that it is crucial to continuously educate medical professionals about new treatment options and the latest treatment insights, ensuring that patients with HCM can quickly progress from primary care to cardiology specialists and receive timely and appropriate treatment.