Webinars

Kristen Hsu, ARC’s Executive Director of Research, shared the latest updates on ATTR (transthyretin amyloidosis) clinical trials and what these developments mean for patients and families. There was also an opportunity for questions and answers.

Original Presentation Date:
January 22, 2026

Download the Slides →

0:00 — Welcome

3:34 — Introduction

5:50 — What is a Clinical Trial?

7:20 — Approaches to ATTR Amyloidosis Treatment

15:00 — ATTR Amyloidosis Clinical Trials

18:19 — ACT-EARLY (ttr stabilizer; asymptomatic carriers of ttr mutations)

25:09 — TRITON-CM (gene silencer; wild-type or hereditary attr-cm)

29:30 — TRITON-PN (gene silencer; hereditary attr-pn)

32:46 — CLEOPATTRA (anti-fibril depleter; wild-type or hereditary attr-cm)

37:27 — Upcoming Milestones in 2026

38:14 — CARDIO-TTRansform (gene silencer; wild-type or hereditary attr-cm)

40:56 — MAGNITUDE/MAGNITUDE-2 (gene editing; wild-type or hereditary attr-cm & attr-pn)

43:43 — How long does FDA approval take after Phase 3?

47:18 — Other Recruiting and Planned Clinical Studies

47:59 — How to Find Clinical Trials

51:50 — Q&A Session

51:56 — What’s the difference between TTR knockdown and stabilizer drugs?

55:02 — Are there any studies showing silencers and stabilizers are beneficial in combination or one is better than the other?

57:10 — Can you share about Attralus’ AT-02 study?

58:24 — Can you share about the Cliramitug/DepleTTR-CM (ALXN220) study?

1:00:49 — Will having an ICD (cardiac defibrilator) implanted exclude me from clinical trials?

1:01:38 — Why do trials exclude normal NT-proBNP levels?

1:03:57 — Are there trials for wild-type ATTR without cardiac involvement?

1:06:15 — Conclusion

Questions Answered After the Webinar:

Q: What’s the difference between TTR knockdown and stabilizer drugs?

A: TTR knockdown agents inhibit production of TTR so that your body doesn’t produce it anymore. Stabilizers work to stabilize the TTR protein so that it does not breakdown and form subunits that then aggregate, misfold, and form amyloid fibrils. Depleters work to remove the existing amyloid fibrils from the organs.

Q: Do the depleters reduce amyloid deposits only in the heart or more generally in the musculoskeletal system?

A: In theory, depleters would remove amyloid deposits from the organs that they form on. The current clinical trials being conducted are specifically looking at the heart.

Q: Are any studies planned for wild-type ATTR with polyneuropathy without cardiac involvement?

A: At this time there are no current studies planned for ATTR Wild-Type that focuses only on polyneuropathy. Many studies of ATTR wild-type include measurements of polyneuropathy, but these are being measured in patients who all have cardiac involvement.

Q: Will the CLEOPATTRA study allow infusion centers that may be closer than the study center to infuse?

A: This will vary depending on the centers conducting the study. You would have to discuss this with the Study Center or contact NovoNordisk directly to inquire about this.

Q: Have you heard of a future study similar to the Cleopatra study for ATTR-PN?

A: At this time, we are not aware of any Phase 3 trials of depleteres (ex: Coramitug, cliramitug) planned for ATTR-PN and if there are, this has not been publicly shared yet. As soon as we learn of new studies, we will let our community know.

Q: Is the “turning off a tap” analogy for silencers or stabilisers?

A: The analogy is used to demonstrate the impact of both silencers and stabilizers. Silencers reduce the amount of protein being produced in the body whereas stabilizers reduce the ability for the protein to breakdown, misfold and develop amyloid fibrils.

Q: What is the earliest these trials could be on the market?

A: The time from trial to market of any drug varies by disease and other factors. Please refer back to the slide deck where we discuss the Phases of a Clinical Trial (slide 9) and the Time to Approval Post Phase 3 study completion (slide 35).

Q: Are there any studies on mortality rate after initial treatments?

A: Studies on mortality rate after initial treatments are currently ongoing. Below you can find published articles related to these specific medications.

i. Tafamidis

a. Survival in a Real-World Cohort of Patients With Transthyretin Amyloid Cardiomyopathy Treated With Tafamidis: An Analysis From the Transthyretin Amyloidosis Outcomes Survey (THAOS)
https://onlinejcf.com/action/showPdf?pii=S1071-9164%2824%2900222-7

b. Understanding how long people with transthyretin amyloid cardiomyopathy (ATTR-CM) live when they take tafamidis as part of their regular healthcare: a plain language summary
https://pubmed.ncbi.nlm.nih.gov/40391408/

ii. Acoramidis

a. Long-Term Efficacy and Safety of Acoramidis in ATTR-CM: Initial Report From the Open-Label Extension of the ATTRibute-CM Trial
https://pubmed.ncbi.nlm.nih.gov/39556242/

Q: What are the best markers to see if Tafamidis treatment is effecive? Can multiple therapy drugs be used at same time?

A: Multiple medications can be used at the same time, with some patients receiving a stabilizer and silencer but we cannot make recommendations on this.

Unfortunately, there is no simple test to check whether Tafamidis is working the way it should and since it slows disease progression, most won’t notice or feel the effects.

Tafamidis efficacy is monitored indirectly by tracking functional cardiac measures (NT-proBNP and troponin) echocardiography (strain, wall thickness, EF) and 6-minute walk test along with symptoms and quality of life (NYHA class, KCCQ, or ATTR-QOL). Dr. Mathew Maurer graciously provided us this information regarding monitoring the effectiveness of tafamidis:

i. Clinical — Heart failure or cardiovascular hospitalization, urgent visits for heart failure or outpatient worsening heart failure, characterized by oral diuretic intensification, NYHA class, days alive out of hospital.

ii. Functional — 6-minute walk test, short physical performance battery (SPPB), cardiopulmonary exercise testing and fraility measures.

iii. Laboratory — Cardiac biomarkers, staging systems, renal function, peralbumin (TTR) evels

iv. Patient Reported Outcomes (PROs) — Kansas City Cardiomyopathy Questionnaire (KCCQ), Compositive Autonomic Symptom Score-31 (Compass-31), European Quality of Life 5 Dimensions 5 Level Version (EQ5D-5L), Short form 12-36 Health Survey Questionnaire (SF12 or SF36), ATTR-QOL

v. Electrocardiographic —  Declining WRS voltage, new arrhythmias or worsening arrhythmia burden, progressive conduction disease, need for permanent pacer.

vi. Imaging — Echo (stroke volume, longitudinal strain, RV function, worsening valvular function), MRI (LV mass, ECV), PET (standardized uptake value, amyloid load).

Q: Will subcutaneous (delivered under the skin) stabilizers ever be able to be injected at home?

A: There currently are no approved subcutaneous treatments for at-home use for ATTR-CM at this time. Some insurance companies will cover an at-home nurse to provide the injection but this is not always approved or covered.

Q: What is the efficacy of green tea capsules (decaf)?

A: Lab work suggests EGCG (a compound in green tea) can bind TTR and affect fibril formation, and small observational studies in wild-type ATTR cardiomyopathy reported stabilization of heart muscle thickness over ~12 months. But these were uncontrolled studies, and green tea hasn’t been shown to prevent progression or replace proven therapies. Major guidelines focus on disease-modifying drugs (e.g., tafamidis) and do not recommend EGCG as standard treatment. If you choose to take a green tea extract, please keep your clinician in the loop and avoid exceeding label doses.

Q: Are there any studies on Vyndamax vs Attrruby?

A: At this time there have been no studies conducted on a head-to-head comparison of Vyndamax vs Attruby.

Q: Does the body need these proteins that the liver forms?

A: Patients who take silencers are often given vitamin A supplements due to the role the TTR protein plays in transmitting vitamin A throughout the body. That being said, we are still studying and learning the long-term implications of knocking down this protein.

Q: Are you aware which trials allow for treatment at home instead of having to go to the doctor’s office?

A: This will vary depending on the centers conducting the study. You would have to discuss this with the Study Center directly to inquire about this.

Q: If gene silencers stop gene production, how are the proteins replaced?

A: If a gene is silenced, the protein is not replaced, which is why it is recommended to take Vitamin A supplementation with some of the silencer medications. Please follow your provider’s guidance.

Q: Will 124I-evuzamitide PET scanning help identify amyloid involvement in other parts of the body?

A: The primary study is looking at the tracer’s ability to identify cardiac amyloid. There has been data showing that it is able to pick up amyloid in other parts of the body.

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