Phase 3 trial is tracking use of acoramidis to block ATTR onset
Study expands sites, actively recruiting high-risk adults currently symptom free
A Phase 3 clinical trial that’s testing the oral treatment acoramidis to prevent or delay disease onset is continuing to recruit adults who carry a mutation known to cause hereditary transthyretin amyloidosis (hATTR), including familial amyloid polyneuropathy (FAP), but aren’t having symptoms yet.
That’s according to a recent update to the ACT-EARLY study (NCT06563895) page, where sites in France, the Netherlands, and Taiwan were added to dozens already open across North America, Europe, and Asia. The study aims to enroll up to 582 people, ages 18 to 75. The first participant was dosed earlier this year.
In ATTR, an abnormal transthyretin protein is produced that forms toxic clumps — called amyloid fibrils — that accumulate in several tissues and cause damage. The disease can be hereditary, where it’s passed down through families due to a mutation in the TTR gene, or wild-type (developing sporadically with age, usually in older adults).
In FAP, or hereditary ATTR with polyneuropathy (ATTR-PN), amyloid fibrils build up mainly in the nerves outside the brain and spinal cord, causing neurological symptoms. When these toxic clumps build up mainly in the heart muscle, they cause ATTR with cardiomyopathy (ATTR-CM), which may not may not be due to mutations.
Acoramidis mechanism and recent approvals
Acoramidis works by stabilizing the TTR protein, preventing it from misfolding and forming amyloid fibrils. This is expected to slow the progression of ATTR or even prevent its onset.
Marketed in the U.S. by BridgeBio Pharma under the brand name Attruby, acoramidis was approved in 2024 for adults with wild-type or hereditary ATTR-CM to reduce death and hospitalization related to heart problems. It was approved in the European Union this year for the same indication, and is marketed there by Bayer as Beyonttra. The therapy is not cleared for use in FAP.
Its approval was based on data from the Phase 3 ATTRibute-CM clinical trial (NCT03860935), which found acoramidis worked better than a placebo at reducing death and hospitalization from heart problems in adults with wild-type or hereditary ATTR-CM.
The ongoing ACT-EARLY study is testing whether acoramidis can prevent or delay the onset of hATTR (FAP and hereditary ATTR-CM). It is sponsored by the therapy’s primary developer, Eidos Therapeutics, which is now owned by BridgeBio.
Participants must be within 10 years of the expected age at which the disease typically begins, based on their family history or genetic mutation. They are randomly assigned to receive oral tablets of either acoramidis (712 mg) or a placebo twice daily for up to seven years, or until the study is closed.
The trial’s main goal is to track the time to developing FAP or hereditary ATTR-CM. FAP is defined by new signs or symptoms along with a diagnosis confirmed by biopsy (a sample of tissue examined under a microscope), whereas ATTR-CM is defined by biopsy and imaging-based diagnosis.
The study is expected to conclude by the end of 2032.
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