BridgeBio Pharma has announced that the first participant has been dosed in ACT-EARLY, a global clinical study designed to investigate whether early intervention can prevent the onset of transthyretin amyloidosis (ATTR) in individuals who carry a pathogenic transthyretin (TTR) variant.

This registrational trial marks the first primary prevention study for ATTR, targeting asymptomatic carriers of a known genetic mutation.

ACT-EARLY is a randomized, double-blind, placebo-controlled, event-driven study aiming to enroll approximately 600 asymptomatic individuals. Participants will receive either acoramidis—a near-complete TTR stabilizer – or placebo, with the primary endpoint being the time to clinical diagnosis of ATTR cardiomyopathy (ATTR-CM) or polyneuropathy (ATTR-PN). Additional measures include safety, tolerability, and biomarker changes such as plasma TTR concentration and neurofilament light chain levels.

According to the company, current treatment options for ATTR are only available after diagnosis and primarily aim to slow disease progression. However, no approved therapies exist for individuals who are genetically predisposed but not yet symptomatic. The hope is that early intervention might delay or even prevent disease manifestation.

The company reported that its previous Phase 3 trial, ATTRibute-CM, showed a 59.1% reduction in risk of all-cause mortality or first cardiovascular-related hospitalization among variant ATTR-CM (ATTRv-CM) patients receiving acoramidis compared to placebo. This finding was disclosed at the American College of Cardiology 2025 Annual Scientific Sessions and is being used to support the mechanistic rationale behind the prevention study. In that trial, treatment effects were seen as early as three months, and post-hoc analyses suggested reductions in recurrent events and hospitalizations over a 30-month period.

Experts involved in ACT-EARLY say the study represents a potentially significant step forward for carriers of the TTR mutation, a group that often faces a prolonged period of uncertainty. “There are still many people who carry a genetic variant which puts them at risk of this progressive and fatal disease,” said Ahmad Masri, director of the cardiac amyloidosis program at Oregon Health & Science University.

“By collaborating on this study, we aim to address that gap in care.”

Patient advocacy organizations are also supporting the effort. “This underserved, at-risk population must currently wait for symptoms to emerge before they can receive any treatment,” said Muriel Finkel, President of Amyloidosis Support Groups. “I’m hopeful this trial can change that reality.”