Acoramidis Received FDA Approval for Treatment of Transthyretin Amyloid Cardiomyopathy

Acoramidis (Attruby; BridgeBio Pharma, Inc) received FDA approval for the treatment of patients with transthyretin amyloid cardiomyopathy (ATTR-CM) to reduce cardiovascular death and cardiovascular-related hospitalization. The decision is based on statistically significant results demonstrated in the phase 3 ATTRibute-CM study (NCT03860935).¹

Cardiomyopathy block letters | Image Credit: © lexiconimages - stock.adobe.com

ATTR-CM is an underdiagnosed, fatal disease of the heart muscle caused by mishappen transthyretin (TTR) proteins that accumulate in the heart, nerves, and other organs. This buildup results in cardiomyopathy, leading to heart failure, typically with preserved ejection fraction. Primary treatment for this disease are agents that bind to TTR, such as tafamidis (Vyndaqel; Pfizer) or diflunisal (Dolobid; Merck Sharp & Dohme).^2,3

“Transthyretin cardiac amyloidosis is a progressive disease with a poor prognosis when left untreated,” Martha Grogan, MD, Mayo Clinic, said in a press release.⁴ “Having a new first-line treatment option which provides excellent TTR stabilization and improves outcomes in this disease gives patients more options. Encouraging data suggests [acoramidi] reduces all-cause mortality and cardiovascular hospitalization as early as three months after initiation of therapy. With continued advances in therapy, this previously fatal disease is becoming a manageable chronic cardiovascular condition.”

Acoramidis is a novel TTR stabilizer that has shown improved potency, binding affinity, binding-site occupancy, binding thermodynamics, and stabilization. In the phase 3, randomized, double-blind, placebo-controlled trial, researchers randomly assigned 632 participants in a 2:1 fashion to receive acoramidis hydrochloride at a dose of 800 mg twice daily or placebo for 30 months.⁵

The primary end points of the study included death from any cause, cardiovascular-related hospitalization, the change from baseline in the N-terminal pro–B-type natriuretic peptide (NT-proBNP) level, and the change from baseline in the 6-minute walk distance. Secondary end points were death from any cause, the 6-minute walk distance, the score on the Kansas City Cardiomyopathy Questionnaire–Overall Summary, and the serum TTR level.⁵

According to data analyses, acoramidis was favored over placebo with a win ratio of 1.8 (95% confidence interval [CI], 1.4 to 2.2), with 63.7% of comparisons favoring acoramidis and 35.9% favoring placebo. Death from any cause and cardiovascular hospitalizations made up 58% of the wins and losses to the win ratio. The highest ratios of wins to losses were observed in NT-proBNP pairwise comparisons (23.3% vs. 7.0%).5

Adverse events (AEs) in the acoramidis and placebo treatment arms were similar(98.1% and 97.6%); serious AEs were reported in 54.6% and 64.9% of the patients, respectively.⁵

The ATTRibute-CM study results highlight the potential of acoramidis to reduce cardiovascular-related events while maintaining a safety profile similar to placebo. This approval represents a step forward in improving outcomes for individuals with ATTR-CM, contributing to the evolving landscape of treatment for this complex disease.

REFERENCES

1. Efficacy and safety of ag10 in subjects with transthyretin amyloid cardiomyopathy (attribute-cm). ClinicalTrials.gov Identifier: NCT03860935. Updated June 27, 2024. Accessed November 25, 2024. https://clinicaltrials.gov/study/NCT03860935

2. Transthyretin amyloid cardiomyopathy (attr-cm). American Heart Association. May 29, 2024. Accessed November 25, 2024. https://www.heart.org/en/health-topics/cardiomyopathy/what-is-cardiomyopathy-in-adults/transthyretin-amyloid-cardiomyopathy-attr-cm

3. Transthyretin amyloidosis (attr-cm). Cleveland Clinic. May 1, 2022. Accessed November 25, 2024. https://my.clevelandclinic.org/health/diseases/17855-amyloidosis-attr#management-and-treatment

4. Attruby™ (acoramidis), a near complete ttr stabilizer (≥90%), approved by fda to reduce cardiovascular death and cardiovascular-related hospitalization in attr-cm patients. BridgeBio. November 22, 2024. Accessed November 25, 2024. https://bridgebio.com/news/attruby-acoramidis-a-near-complete-ttr-stabilizer-%E2%89%A590-approved-by-fda-to-reduce-cardiovascular-death-and-cardiovascular-related-hospitalization-in-attr-cm-patients/

5. Gillmore J, Judge D, Cappelli F, et al. Efficacy and safety of acoramidis in transthyretin amyloid cardiomyopathy. N Engl J Med. January 10, 2024. Accessed November 25, 2024. https://www.nejm.org/doi/full/10.1056/NEJMoa2305434