The Amyloidosis Research Consortium recently hosted a webinar to explore the many therapies that are available or in development for transthyretin amyloid cardiomyopathy (ATTR-CM).
The discussion was led by Dr. Jan Griffin, a cardiologist at the Medical University of South Carolina (MUSC) who specializes in amyloidosis. Griffin is also the director of MUSC’s Amyloidosis Center of Excellence.
During her talk, Griffin provided an overview of several classes of therapies for ATTR-CM, along with data highlighting their safety and efficacy.
Transthyretin stabilizers
Transthyretin stabilizers prevent the transthyretin protein from breaking down and accumulating in the heart.
Read more about ATTR-CM therapies
In 2019, tafamidis became the first drug approved for patients with ATTR-CM. Approval was granted based on the ATTR-ACT clinical trial, which demonstrated the superiority of tafamidis versus a placebo.
Acoramidis is another transthyretin stabilizer and was approved in November 2024 for ATTR-CM. The ATTRibute-CM study enrolled 632 patients with ATTR-CM and found that acoramidis significantly reduced the risk of death or cardiovascular hospitalizations compared to a placebo.
The ACT-EARLY trial will assess whether acoramidis can prevent symptom onset. The trial is currently enrolling patients who do not have symptoms of ATTR-CM but have a mutation in the transthyretin gene known to cause the disease.
Transthyretin silencers
Transthyretin silencers inactivate the transthyretin gene so that no transthyretin protein can be produced. Patients taking transthyretin silencers must also take vitamin A supplements, as transthyretin plays a role in vitamin A transport, explained Griffin.
Vutrisiran was approved for patients with ATTR-CM in March 2025 following positive results of the HELIOS-B study. The drug is administered via injection once every three months by a medical professional.
Eplontersen is currently being investigated in the Cardio-TTRansform trial. This drug is self-administered via injection once per month.
Transthyretin-depleting agents
Transthyretin-depleting agents aim to remove the amyloid that has already accumulated in the organs of patients with ATTR-CM.
ALXN2220 is administered every four weeks via intravenous infusion. A Phase 1 clinical trial showed that the drug successfully removed amyloid deposits from the heart. A Phase 3 clinical trial is currently being conducted to evaluate whether the drug improves life expectancy and quality of life in a cohort of 1,181 patients.
Coramitug is another depleting agent being investigated for ATTR-CM. Clinical trial results are expected by late 2025.
Gene therapy
Nex-z is a gene editing drug that removes the transthyretin gene from the patient’s DNA. The goal of this treatment is to provide a drug that cures the disease with a single dose.
Phase 1 clinical trial results have shown that nex-z significantly decreases transthyretin levels up to two years after administration and improves quality of life.
Other considerations
When asked how to decide on a treatment, Griffin explained that there is no simple answer to this question. “We cannot compare the drugs that we have available to us at this time,” she said. “[There have] been no head-to-head comparison between any of these agents.”
Griffin advised that patients speak with their physician to determine the best course of action. Important considerations may include cost, dosing schedule and method of administration.
Patients should also consult their doctors about adding mineralocorticoid receptor antagonists or loop diuretics to their treatment plans to address fluid retention, Griffin said.
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