FDA Approves Attruby (Acoramidis) for ATTR-CM, Reducing Cardiovascular Death and Hospitalization
核心洞察
The FDA has approved Attruby (acoramidis) for treating adults with transthyretin (搜索)-mediated amyloid cardiomyopathy (ATTR-CM (搜索)), addressing both wild-type and variant forms of the disease.
Attruby, an oral TTR stabilizer, demonstrated a significant reduction in cardiovascular death and cardiovascular-related hospitalizations in the Phase 3 ATTRibute-CM trial.
The approval marks Attruby as the first and only therapy with a label specifying near-complete stabilization of transthyretin (搜索) (TTR), targeting the underlying cause of ATTR-CM (搜索).
The U.S. Food and Drug Administration (FDA) has approved Attruby (acoramidis), an orally administered transthyretin (搜索) (TTR) stabilizer, for the treatment of adult patients with cardiomyopathy of wild-type or variant transthyretin-mediated amyloidosis (ATTR-CM (搜索)). This approval marks a significant advancement in the treatment of ATTR-CM, a progressive disease associated with high mortality and morbidity.
The approval is based on the positive results from the ATTRibute-CM Phase 3 study, which demonstrated that Attruby significantly reduced cardiovascular death and cardiovascular-related hospitalization, while also improving the quality of life for patients. The trial enrolled 632 participants with symptomatic ATTR-CM (搜索), who were randomized in a 2:1 ratio to receive Attruby or placebo for 30 months.
Clinical Efficacy and Safety
The ATTRibute-CM trial met its primary endpoint, demonstrating a statistically significant treatment effect with a Win Ratio of 1.8 (p<0.0001) on a 4-component composite endpoint of all-cause mortality (ACM), cardiovascular hospitalization (CVH), N-terminal prohormone of brain natriuretic peptide (NT-proBNP (搜索)), and 6-minute walk distance. Acoramidis also showed statistically significant improvements in the Kansas City Cardiomyopathy Questionnaire and 6-minute walk test at 30 months. The increase in NT-proBNP on treatment was approximately half that of placebo.
According to Martha Grogan, M.D., of the Mayo Clinic, transthyretin (搜索) cardiac amyloidosis is a progressive disease with a poor prognosis when left untreated and Attruby provides an excellent TTR stabilization and improves outcomes. Data suggests Attruby reduces all-cause mortality and cardiovascular hospitalization as early as three months after initiation of therapy.
In terms of safety, the most common adverse reactions reported in patients treated with Attruby were diarrhea (11.6% vs 7.6%) and upper abdominal pain (5.5% vs 1.4%) compared to placebo. These adverse reactions were generally mild and resolved without drug discontinuation. Discontinuation rates due to adverse events were similar between the Attruby and placebo groups (9.3% and 8.5%, respectively).
Mechanism of Action
Attruby is designed to mimic a naturally occurring "rescue mutation" of the TTR gene (T119M) that targets the root cause of ATTR-CM (搜索): destabilization of the native TTR tetramer. By achieving near-complete (≥90%) TTR stabilization, Attruby preserves the native function of TTR as a transport protein for thyroxine and vitamin A, thereby improving cardiovascular outcomes.
Regulatory and Commercialization Plans
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 (搜索) in Europe.
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. ForgingBridges includes insurance resources, financial assistance options and a dedicated support team to assist in the treatment journey.