The U.S. Food and Drug Administration (FDA) has approved Attruby (acoramidis) for the treatment of adult patients with transthyretin amyloid cardiomyopathy (ATTR-CM), marking a significant advancement in the management of this rare and progressive disease. The approval, announced by BridgeBio Pharma, is based on the positive results from the ATTRibute-CM Phase 3 study, which demonstrated a significant reduction in cardiovascular death and cardiovascular-related hospitalization, along with improvements in the quality of life for patients.
Clinical Efficacy and Safety
The ATTRibute-CM Phase 3 study enrolled 632 participants with symptomatic ATTR-CM, who were randomized in a 2:1 ratio to receive either Attruby or placebo for 30 months. The trial met its primary endpoint, demonstrating a statistically significant treatment effect with a Win Ratio of 1.8 (p<0.0001) on a four-component composite endpoint of all-cause mortality (ACM), cardiovascular hospitalization (CVH), N-terminal prohormone of brain natriuretic peptide (NT-proBNP), and six-minute walk distance. Attruby also showed a statistically significant treatment effect at 30 months on the Kansas City Cardiomyopathy Questionnaire and six-minute walk test. The increase in NT-proBNP on treatment was approximately half that of placebo.
Attruby was generally well-tolerated, with most side effects being mild, including diarrhea and abdominal pain, which typically resolved without the need for 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
ATTR-CM is characterized by the misfolding and aggregation of the transthyretin (TTR) protein, leading to the formation of amyloid deposits in the heart. Attruby (acoramidis) functions as a TTR stabilizer, preventing the protein from misfolding and aggregating. It was designed to mimic a naturally occurring "rescue mutation" of the TTR gene (T119M) that targets the root cause of ATTR-CM, the destabilization of the native TTR tetramer. By stabilizing TTR, Attruby preserves its native function as a transport protein for thyroxine and vitamin A, thereby benefiting cardiovascular outcomes.
Impact on Patient Care
The approval of Attruby offers a crucial new treatment option for patients with ATTR-CM, a condition that, if left untreated, carries a poor prognosis. According to Martha Grogan, MD, of the Mayo Clinic, Attruby not only provides excellent TTR stabilization but also improves outcomes, potentially transforming this previously fatal disease into a manageable chronic cardiovascular condition. Data suggests that Attruby reduces all-cause mortality and cardiovascular hospitalization as early as three months after initiation of therapy.
Access and Support
BridgeBio is committed to ensuring patient access to Attruby through the ForgingBridges™ program, which offers insurance resources, financial assistance options, and a dedicated support team. The company will also provide Attruby free for life to those who participated in the clinical trials. The list price for Attruby is $18,759.12 for a 28-day supply; however, commercial patients may be eligible for a $0 copay, while Medicare patients will have a maximum copay of $167 per month.
Future Directions
BridgeBio is also pursuing approvals for acoramidis globally, with submissions planned for Europe, Japan, and Brazil. In Europe, BridgeBio has granted exclusive rights to Bayer to commercialize acoramidis for ATTR-CM. A decision from the European Medicines Agency is expected in 2025.
