On April 2, Dr. Milind Desai and colleagues from the Cleveland Clinic Heart Vascular & Thoracic Institute presented their findings from the VALOR-HCM study at the American College of Cardiology’s 71st Annual Scientific Session in Washington, D. C. This study, which was sponsored by MyKardia, a subsidiary of Bristol Myers Squibb (BMS), sought to explore the efficacy of BMS’s mavacamten as an alternative to surgical myectomy or alcohol septal ablation in patients with obstructive hypertrophic cardiomyopathy (HCM). Obstructive HCM has never before been the target of clinical trial development, and mavacamten would be the first drug to be specifically indicated for the disease. As such, GlobalData believes that BMS stands to gain a significant patient share since mavacamten would be first to market for obstructive HCM and first in its class as a myosin inhibitor. Dr. Desai’s study results highlight the strength of the drug candidate, as findings indicate nearly 80% of participants in the mavacamten study group no longer needed to pursue surgical intervention after the 16-week period.

Cardiomyopathy refers to a diverse set of diseases that make it difficult for the heart to pump blood to the rest of the body, sometimes resulting in heart failure. There are four main types of cardiomyopathies: dilated cardiomyopathy (DCM), HCM, restrictive cardiomyopathy, and arrhythmogenic cardiomyopathy. Each subtype has its own unique etiology and pathophysiology, but general symptoms include shortness of breath; difficulty lying flat to sleep; fatigue; rapid or fluttering heartbeats; swelling of the legs, ankles, and feet; and more. Cardiomyopathies can be diagnosed through ambulatory monitoring, cardiac magnetic resonance imaging, electrocardiograms, exercise stress tests, and myocardial biopsy. They are either genetically inherited or acquired over a patient’s lifetime as a result of another condition. While cardiomyopathy cannot be cured, the indication can be managed with drugs such as angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, diuretics, antiarrhythmics, sodium-glucose co-transporter 2 inhibitors, and more.

Of the four main types of cardiomyopathies, HCM and DCM are the most common. HCM is further segmented into obstructive and non-obstructive forms, which are differentiated based on whether blood flow within the heart is blocked. Depending on the severity of the case, patients with obstructive HCM may be provided with therapeutics or surgical intervention. In discussing obstructive HCM patients, a GlobalData key opinion leader shared the following:

“In the case of obstructive disease, there’s the possibility of surgical ablation, surgical resection of part of the ventricle, or an alcohol ablation where alcohol is infused into the coronary artery. And that would only be done after medical therapy failed. So, the therapy of obstructive and non-obstructive starts out about the same. In both cases, you’re generally dealing with patients who have heart failure symptoms, and you’re trying to decrease the heart failure symptoms by titrating the drugs, which decrease either the obstruction or just simply the resistance to filling. I’d say those therapies are more effective in obstructive disease because…we have a [clearer] target of therapy, which is to reduce the obstruction.”

US Key Opinion Leader

The VALOR-HCM Phase III trial enrolled 112 symptomatic HCM patients, all of whom were previously suggested to pursue surgical myectomy or alcohol ablation for their obstruction. Participants were randomized to receive either mavacamten at 5g to 15mg daily or an oral placebo (PBO). The researchers found that after 16 weeks, 76.8% of PBO participants (43 out of 56) continued to meet the guideline for surgery, or elected to undergo surgery, compared to 17.9% of participants receiving mavacamten (10 out of 56). These results demonstrated not only the efficacy of the drug candidate, but also the ability for patients with obstructive HCM to avoid invasive and costly procedures by using an oral medication alternative. The majority of patients also requested to continue the drug after the 16-week study period, suggesting a favorable safety profile. Market launch of mavacamten is anticipated for this calendar year, and Dr. Desai’s study results give obstructive HCM patients reasons to be excited.