The U.S. Food and Drug Administration (FDA) has approved Attruby™ (acoramidis), an orally-administered near-complete (≥90%) stabilizer of Transthyretin (TTR), for the treatment of adults with transthyretin amyloid cardiomyopathy (ATTR-CM) to reduce cardiovascular death and cardiovascular-related hospitalization. This approval marks a significant advancement in the treatment of ATTR-CM, a progressive and often fatal disease. The approval is based on the positive results from the ATTRibute-CM Phase 3 study.
Clinical Trial Results
The ATTRibute-CM Phase 3 study, which enrolled 632 participants with symptomatic ATTR-CM, demonstrated that Attruby significantly reduced the composite endpoint of all-cause mortality (ACM) and recurrent cardiovascular-related hospitalizations (CVH) by 42% at Month 30 compared to placebo (p<0.0001). The study also revealed a 50% reduction in the cumulative frequency of CVH events relative to placebo at Month 30. Notably, benefits were observed as early as 3 months into treatment, showing the most rapid benefit seen in any Phase 3 study of ATTR-CM to date.
Mechanism of Action and TTR Stabilization
Attruby is the first and only approved product with a label specifying near-complete stabilization of TTR. It was designed to mimic a naturally occurring "rescue mutation" of the TTR gene (T119M) that targets the root cause of ATTR-CM, destabilization of the native TTR tetramer. Through near-complete TTR stabilization (≥90%), Attruby has been shown to preserve the native function of TTR as a transport protein of thyroxine and vitamin A and to demonstrate benefit on cardiovascular outcomes.
Expert Commentary
"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, M.D., 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."
Safety and Tolerability
Attruby was generally well-tolerated in the clinical trial. The most common adverse reactions reported in patients treated with Attruby versus placebo were diarrhea (11.6% vs 7.6%) and upper abdominal pain (5.5% vs 1.4%). The majority of these adverse reactions were mild and resolved without drug discontinuation. Discontinuation rates due to adverse events were similar between patients treated with Attruby versus placebo (9.3% and 8.5%, respectively).
Commercialization and Access
BridgeBio offers a patient support services program, ForgingBridges™, for people in the U.S. prescribed Attruby and their families to receive help accessing this new therapy. With this approval, BridgeBio will receive a $500 million payment under their royalty funding agreement. BridgeBio has submitted a Marketing Authorization Application to the European Medicines Agency, with a decision expected in 2025. BridgeBio has granted exclusive rights to Bayer to commercialize acoramidis for ATTR-CM in Europe.
