FDA Approves Attruby (Acoramidis) for ATTR-CM, Showing Rapid Reduction in Cardiovascular Events
核心洞察
The FDA has approved Attruby (acoramidis) for treating adults with transthyretin (搜索) amyloid cardiomyopathy (ATTR-CM (搜索)) to reduce cardiovascular death and hospitalization.
Attruby is the first and only approved therapy with a label specifying near-complete stabilization (≥90%) of transthyretin (搜索) (TTR), preserving its native function.
Clinical trials demonstrated that Attruby significantly reduced all-cause mortality and cardiovascular-related hospitalizations, with benefits observed as early as three months.
The U.S. Food and Drug Administration (FDA) has granted approval to Attruby™ (acoramidis), an orally administered, near-complete (≥90%) stabilizer of transthyretin (搜索) (TTR), for the treatment of adults with transthyretin amyloid cardiomyopathy (ATTR-CM (搜索)). This approval marks a significant advancement in the treatment of ATTR-CM, offering a new option to reduce cardiovascular death and cardiovascular-related hospitalization.
The FDA's decision was based on the positive outcomes from the ATTRibute-CM Phase 3 study, which demonstrated that Attruby significantly reduced mortality and cardiovascular hospitalization while also improving the quality of life for patients. The study, published in The New England Journal of Medicine, enrolled 632 participants with symptomatic ATTR-CM (搜索), associated with either wild-type or variant TTR, who were randomized 2:1 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-related hospitalization (CVH), N-terminal prohormone of brain natriuretic peptide (NT-proBNP), and 6-minute walk distance. Furthermore, Attruby exhibited a statistically significant treatment effect at 30 months on the Kansas City Cardiomyopathy Questionnaire and 6-minute walk test. 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 (搜索) 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. 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."
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 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 (搜索): destabilization of the native TTR tetramer. By near-completely stabilizing TTR, Attruby preserves its native function as a transport protein for thyroxine and vitamin A, demonstrating benefits on cardiovascular outcomes.
Patient Support and Access
BridgeBio offers a patient support program called ForgingBridges™ to assist U.S. patients prescribed Attruby and their families. This program includes insurance resources, financial assistance options, and a dedicated support team. In addition, BridgeBio will provide Attruby free for life to U.S. clinical trial participants, honoring their contribution to the drug's development.
Future Plans
BridgeBio has submitted a Marketing Authorization Application to the European Medicines Agency, with a decision expected in 2025. They have also granted exclusive rights to Bayer to commercialize acoramidis for ATTR-CM (搜索) in Europe. Neil Kumar, Ph.D., founder and CEO of BridgeBio, expressed excitement about the approval, stating, "With the landmark approval of Attruby, we gain the ability to serve patients with ATTR-CM... Our journey is not over as we look to pursue approvals globally, next in Europe, Japan, and Brazil, and to continue exploring the full potential of this treatment."