First asymptomatic participant with a known pathogenic transthyretin (TTR) variant has been dosed in ACT-EARLY with acoramidis.-Bridge Bio

- BridgeBio Pharma, Inc. diseases, announced that the first asymptomatic participant with a known pathogenic transthyretin (TTR) variant, that may lead to transthyretin amyloid disease (either cardiomyopathy, ATTR-CM, polyneuropathy, ATTR-PN, or both), has been dosed in ACT-EARLY with acoramidis. Acoramidis is a selective, small molecule, orally administered near-complete (≥90%) TTR stabilizer.

“Launching ACT-EARLY is part of our ongoing commitment to further the genetic understanding of the variants causing ATTR and to ensure patients from around the world have access to optimal care. Our hope is that this study will have profound impact to patients and caregivers, and we look forward to growing our partnership with providers and patient advocacy organizations to establish a new prevention paradigm in an area where there is serious unmet need,” said Adam Castaño, M.D., Vice President of Global Clinical Development at BridgeBio Cardiorenal and Head of the ACT-EARLY clinical program.

ACT-EARLY is the first ever primary prevention study for ATTR, testing the hypothesis that prophylactic treatment of asymptomatic carriers of a pathogenic TTR variant with the near-complete TTR stabilizer, acoramidis, could delay the onset or prevent the development of variant ATTR (ATTRv), also known as hereditary ATTR (hATTR). ATTRv often presents earlier and progresses more aggressively than the wild-type form of ATTR, leading to significantly worse prognosis. The study aims to randomize ~600 asymptomatic carriers of a pathogenic TTR variant. The primary efficacy endpoint is time to development of ATTR-CM and/or ATTR-PN. Additional endpoints include safety and tolerability of acoramidis, and its effects on cardiac imaging parameters, plasma TTR concentration, nerve conduction and neurofilament light chain.

“Current approved therapies for ATTR amyloidosis are only approved to treat diagnosed disease and can only be expected to slow disease progression. There are still many people who carry a genetic variant which puts them at risk of this progressive and fatal disease, and who typically watched other family members suffer through it. Currently, there are no proven prevention treatment options,” said Ahmad Masri, M.D., M.S., Cardiomyopathy Section Head and Director of the Cardiac Amyloidosis Program at Oregon Health & Science University. “By collaborating with BridgeBio on this groundbreaking study, I am hopeful that we can fill the significant gap in care for asymptomatic carriers of a genetic variant by providing potential preventative intervention early with resulting greater clinical benefit than addressing the disease at a later stage.”

In ATTR-CM patients, independent of genotype, the ATTRibute-CM Phase 3 trial showed separation at 3 months in time to first event (all-cause mortality (ACM) or cardiovascular-related hospitalization (CVH)) of acoramidis relative to placebo. In a post-hoc analysis, acoramidis led to a 42% reduction in composite ACM and recurrent CVH events relative to placebo at Month 30. Furthermore, acoramidis showed a 50% reduction in the cumulative frequency of CVH events relative to placebo at Month 30.

At the American College of Cardiology (ACC) 2025 Annual Scientific Sessions & Expo, BridgeBio disclosed that acoramidis achieved statistical significance in reducing the risk of ACM or first CVH versus placebo in the ATTRv-CM (59.1% risk reduction) subgroup. This treatment effect represents the greatest observed benefit to date for ATTRv-CM patients and establishes the mechanistic hypothesis that stabilization of tetrametric TTR with a near-complete TTR stabilizer, acoramidis, could delay or prevent ATTRv.

“I have met many families of those diagnosed with hereditary ATTR and one question often asked is what can be done for asymptomatic carriers of the genetic variant causing ATTR. Since there is currently no approved therapy to delay or prevent disease onset, this underserved, at-risk population must wait for the development of symptoms before therapy can be prescribed,” said Muriel Finkel, President of Amyloidosis Support Groups, a non-profit organization dedicated to the support of amyloidosis patients and caregivers. “I am hopeful that with ACT-EARLY, loved ones of those with variant ATTR will be able to get genetic testing done, and if they meet the qualification criteria, can get started on a clinical trial that might identify whether prophylactic treatment will slow down or prevent ATTR at its genetic source.”

Acoramidis is approved as Attruby by the U.S. FDA and is approved as BEYONTTRA by the European Commission, Japanese Pharmaceuticals and Medical Devices Agency, and UK Medicines and Healthcare Products Regulatory Agency with all labels specifying near-complete stabilization of TTR.