Acoramidis for Amyloidosis

Recruiting at 4 trial locations

Overseen By Medical Information

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Eidos Therapeutics, a BridgeBio company

Must not be taking: TTR modifying therapies

Disqualifiers: ATTR-CM, ATTR-PN, Major organ dysfunction, others

Pivotal Trial (Near Approval)

Prior Safety Data

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

Transthyretin amyloidosis (ATTR) is a disease where the normally occurring transthyretin (TTR) protein falls apart and forms amyloid, a sticky plaque- like substance that accumulates in different organs in the body and can cause damage to the organ. There are two ways that the TTR protein can fall apart. One way occurs as a person ages, where the normal TTR protein can fall apart and form amyloid that may no longer be sufficiently cleared by the body. This type of ATTR is known as wild-type ATTR (ATTRwt). The other way occurs when a person inherits a defective TTR gene that causes the TTR protein to spontaneously fall apart. This form of the disease is known as variant ATTR (ATTRv) and can be detected in adults by a genetic test of their TTR gene before they age. Amyloid build-up in the heart causes the heart wall to become thick and stiff and can result in heart failure and even death. Accumulation of TTR amyloid in the heart is known as transthyretin amyloid cardiomyopathy or ATTR-CM. Amyloid can also deposit in the nerve tissues leading to nerve problems. Accumulation of TTR in the nerves is known as transthyretin amyloid polyneuropathy or ATTR-PN. Acoramidis is an experimental drug designed to bind tightly to TTR in the blood and stabilize its structure, so it does not form the harmful amyloid plaques that can cause damage to organs. This study is intended to determine if treatment with acoramidis in participants with ATTRv who have not yet developed any symptoms of disease can prevent or delay the development of ATTR-CM or ATTR-PN disease. If adults with an inherited defective TTR gene are treated early before any of the symptoms of disease have developed, it may be possible to delay the onset or prevent the disease entirely.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are currently or have previously been treated with other TTR modifying therapies, you would not be eligible to participate.

How is the drug Acoramidis different from other treatments for amyloidosis?

Acoramidis is unique because it is designed to stabilize transthyretin (TTR), a protein that misfolds in amyloidosis, potentially slowing disease progression. This mechanism is similar to tafamidis, but Acoramidis may offer different dosing or formulation advantages. ^{1 2 3 4 5}

Eligibility Criteria

This trial is for men and women aged 18 to 75 who carry a pathogenic TTR gene variant but have no symptoms of transthyretin amyloidosis, which can lead to heart failure or nerve problems. They must be within 10 years of the age when symptoms typically start.

Inclusion Criteria

Key

I am within 10 years of the PADO's age.

My genetic test shows I have a TTR gene variant linked to disease.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive acoramidis or placebo to prevent or delay the development of ATTR-CM or ATTR-PN

Up to 7 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Acoramidis (Stabilizer)

Trial Overview The study tests if acoramidis, an experimental drug that stabilizes TTR protein in blood, can prevent or delay heart disease (ATTR-CM) or nerve damage (ATTR-PN) in people with genetic risk but no symptoms yet. Participants will either receive acoramidis or a placebo tablet.

Participant Groups

Group I: acoramidis Experimental Treatment 1 Intervention

Participants will receive acoramidis 712 mg orally BID (which is equivalent to 800 mg acoramidis HCl BID)

Group II: Placebo Placebo Group 1 Intervention

Subjects will receive placebo to match twice daily

Who Is Running the Clinical Trial?

Eidos Therapeutics, a BridgeBio company

Lead Sponsor

Trials

12

Recruited

2,400+

Findings from Research

In a study of 82 Japanese patients with wild-type transthyretin cardiac amyloidosis (ATTRwt CA), tafamidis was safely administered to 38 patients, showing no discontinuation due to adverse events and a high 1-year survival rate of 92%.

Patients treated with tafamidis maintained stable disease markers over 12-18 months, indicating that tafamidis may effectively preserve heart function and disease status in the short term for selected patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early Experience of Tafamidis Treatment in Japanese Patients With Wild-Type Transthyretin Cardiac Amyloidosis From the Kochi Amyloidosis Cohort. Ochi, Y., Kubo, T., Baba, Y., et al.[2022]

In patients with transthyretin amyloidosis with polyneuropathy (ATTR-PN), long-term treatment with tafamidis showed a significant survival benefit, with 85.9% of Val30Met patients alive after 9 years when treated continuously with tafamidis.

For non-Val30Met patients, 75.9% were alive after 8 years, indicating that tafamidis may also be beneficial for this group, although survival rates were lower compared to Val30Met patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of Mortality During Long-Term Treatment with Tafamidis for Transthyretin Amyloidosis with Polyneuropathy: Clinical Trial Results up to 8.5 Years. Merlini, G., Coelho, T., Waddington Cruz, M., et al.[2020]

Tafamidis significantly reduces all-cause mortality and cardiovascular-related hospitalizations in patients with transthyretin amyloid cardiomyopathy (ATTR-CM), with a median follow-up of 51 months from the ATTR-ACT trial and its long-term extension study.

The 80 mg dose of tafamidis showed a greater survival benefit compared to the 20 mg dose, while both doses had a safety profile comparable to placebo, suggesting that 80 mg is the optimal dose for treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of tafamidis doses in the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT) and long-term extension study. Damy, T., Garcia-Pavia, P., Hanna, M., et al.[2021]

In a phase II study involving 21 patients with non-Val30Met transthyretin amyloidosis, tafamidis 20 mg once daily effectively stabilized TTR levels in 94.7% of patients by Week 6, and 100% at Months 6 and 12.

While some patients experienced worsening neurological function, tafamidis was well tolerated and did not lead to significant declines in quality of life or other health markers over the 12-month treatment period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of tafamidis on transthyretin stabilization and clinical outcomes in patients with non-Val30Met transthyretin amyloidosis. Merlini, G., Planté-Bordeneuve, V., Judge, DP., et al.[2021]

Tafamidis is an effective treatment for transthyretin amyloidosis (ATTR), approved for use in over 40 countries, and has shown to stabilize the disease's progression in adults with early-stage symptomatic ATTR polyneuropathy and cardiomyopathy.

A phase 1 study involving 30 healthy volunteers demonstrated that the new tafamidis 61-mg free acid capsules are bioequivalent to the standard 80-mg tafamidis meglumine capsules, with both formulations showing a good safety and tolerability profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Bioequivalence of Tafamidis 61-mg Free Acid Capsules and Tafamidis Meglumine 4 × 20-mg Capsules in Healthy Volunteers. Lockwood, PA., Le, VH., O'Gorman, MT., et al.[2021]

References

1. Japan pubmed.ncbi.nlm.nih.gov

Early Experience of Tafamidis Treatment in Japanese Patients With Wild-Type Transthyretin Cardiac Amyloidosis From the Kochi Amyloidosis Cohort. [2022]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Evaluation of Mortality During Long-Term Treatment with Tafamidis for Transthyretin Amyloidosis with Polyneuropathy: Clinical Trial Results up to 8.5 Years. [2020]

3. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of tafamidis doses in the Tafamidis in Transthyretin Cardiomyopathy Clinical Trial (ATTR-ACT) and long-term extension study. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Effects of tafamidis on transthyretin stabilization and clinical outcomes in patients with non-Val30Met transthyretin amyloidosis. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

The Bioequivalence of Tafamidis 61-mg Free Acid Capsules and Tafamidis Meglumine 4 × 20-mg Capsules in Healthy Volunteers. [2021]