FDA Approves Acoramidis (Attruby) for ATTR-CM

The US Food and Drug Administration has approved acoramidis (Attruby) for the treatment of adults with transthyretin amyloid cardiomyopathy (ATTR-CM) to reduce cardiovascular death and cardiovascular-related hospitalization, according to a release from BridgeBio Pharma.

Announced on November 22, 2024, the FDA approval of acoramidis, an orally-administered near-complete (≥90%) stabilizer of TTR, becomes the first and only approved product with a label specifying near-complete stabilization of TTR.

"Transthyretin cardiac amyloidosis is a progressive disease with a poor prognosis when left untreated. Having a new first line treatment option which provides excellent TTR stabilization and improves outcomes in this disease gives patients more options,” said Martha Grogan, MD, of the Mayo Clinic. “Encouraging data suggests Attruby 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."

The approval of acoramidis comes less than 10 months after BridgeBio Pharma announced the FDA’s acceptance of their New Drug Application (NDA) in February 2024. The phase 3 ATTRibute-CM trial, which served as the basis of NDA from BridgeBio, was a double-blind, placebo-controlled trial launched in 2019 with the intent of exploring the safety and efficacy of acoramidis in adult patients with ATTR-CM over the course of 30 months.

The trial included 632 patients. This cohort had a mean age of 77.6 (Standard deviation [SD], 6.6) years, 90.2% were men, and 90.3% had wild-type TTR. Randomizing patients in a 2:1 ratio to either acoramidis hydrochloride at a dose of 800 mg twice daily or matching placebo, the trial leveraged a 4-step primary hierarchical analysis as the primary outcome of interest. This analysis included death from any cause, cumulative frequency of cardiovascular-related hospitalization, change in baseline NT-proBNP level, and change in 6-minute walking distance.

At 30 months, the trial’s primary analysis favored acoramidis relative to placebo, with a win ratio of 1.8 (95% CI, 1.4 to 2.2; P <.001) and 63.7% of pairwise comparisons favoring acoramidis compared to 35.9% favoring placebo. Further analysis indicated death from any cause and cardiovascular-related hospitalization contributed more than half the wins and losses to the win ratio (58% of all pairwise comparisons) while NT-proBNP pairwise comparisons yielded the highest ratio of wins to losses (23.3% vs 7.0%).

In their release announcing approval, BridgeBio Pharma noted of acoramidis was associated with a 42% reduction in composite all-cause mortality and recurrent cardiovascular-related hospitalization events relative to placebo at Month 30 and a 50% reduction in the cumulative frequency of cardiovascular-related hospitalization events relative to placebo at month 30.

“We are excited to be part of the celebration for the FDA approval of Attruby. The need for more treatment options for patients living with ATTR-CM is crucial to achieving the goal of better outcomes and improved quality of life. Access to this new therapy means more hope and more opportunity to improve the lives of patients with amyloidosis,” said Muriel Finkel, President of Amyloidosis Support Groups, a non-profit organization dedicated to the support of amyloidosis patients and caregivers.

During the American Heart Association Annual Scientific Sessions 2024, we sat down with ATTRibute-CM investigator Ahmad Masri, MD, MS, director of the Hypertrophic Cardiomyopathy Center at Oregon Health and Science University, for his perspective on what an approval would mean for patients, providers, and health systems.

Relevant disclosures for Masri include Cytokinetics, Bristol Myers Squibb, BridgeBio, Pfizer, Ionis, Lexicon, Attralus, Alnylam, Haya, Alexion, BioMarin, and AstraZeneca.

References:

1. BridgeBio Pharma. AttrubyTM (acoramidis), a near complete TTR stabilizer (≥90%), approved by FDA to reduce cardiovascular death and cardiovascular-related hospitalization in attr-cm patients. BridgeBio Pharma. November 22, 2024. Accessed November 22, 2024. https://investor.bridgebio.com/news-releases/news-release-details/attrubytm-acoramidis-near-complete-ttr-stabilizer-90-approved.
2. Campbell P. FDA accepts NDA submission for Acoramidis in attr-cm. HCP Live. February 5, 2024. Accessed November 22, 2024. https://www.hcplive.com/view/fda-accepts-nda-submission-for-acoramidis-in-attr-cm.