Failed trial knocks back wider use of BMS' Camzyos

Bristol-Myers Squibb's Camzyos has been growing fast as a treatment for hypertrophic cardiomyopathy (HCM), but – with competition looming – its plans to broaden its approved indications have suffered a setback.

Camzyos (mavacamten) has been used since 2022 as a treatment for obstructive forms of HCM, a disease characterised by thickening of cardiac muscle and stiffness in the left ventricle that interferes with the function of the heart, and remains the only FDA-approved treatment.

BMS had been hoping to expand the label for the first-in-class cardiac myosin inhibitor to include non-obstructive HCM – a milder form of the disease in which there is no obstruction in blood flow from the heart to the body – but a much-anticipated phase 3 trial has ended in failure.

The ODYSSEY-HCM trial in class II-III non-obstructive HCM revealed no statistically significant improvement over placebo in two primary endpoints - the Kansas City Cardiomyopathy Questionnaire – Clinical Summary Score (KCCQ-23 CSS) and peak oxygen consumption (pVO2) – at week 48.

Moreover, the investigators think the finding suggests that obstructive and non-obstructive HVM should be classified as two distinct diseases, requiring different treatment strategies.

"Through long-term trials and real-world data from thousands of patients with symptomatic obstructive HCM, we have seen the meaningful impact that Camzyos has on improving the quality of life for patients living with this condition," commented Milind Desai, an HCM specialist at the Cleveland Clinic in the US.

"ODYSSEY-HCM indicates that we must consider new ways of thinking about potential treatment approaches for non-obstructive HCM."

The result is a major disappointment for BMS as it effectively cuts the potential market for Camzyos in half. Sales of the drug rose by more than 160% last year to reach $602 million, placing it on a clear trajectory for blockbuster sales from the obstructive HCM indication alone.

That said, BMS has previously suggested that approval in non-obstructive HCM could hike double its peak sales projections from $2 billion to $4 billion. In the meantime, the company is faced with its first competition as the FDA is currently reviewing a marketing application for Cytokinetics' aficamten in obstructive HCM, with a decision due by 26th September.

HCM affects one in every 500 people in the US and around 400,000 to 600,000 people worldwide, although, it is under-diagnosed and many patients don't display symptoms. If not treated effectively, it can lead to atrial fibrillation, stroke, and heart failure.

Camzyos was the main asset in BMS' acquisition of MyoKardia for $13 billion in 2020.