The U.S. Food and Drug Administration (FDA) has approved acoramidis (Attruby; BridgeBio Pharma) for the treatment of adult patients with transthyretin amyloid cardiomyopathy (ATTR-CM), marking a significant advancement in the management of this progressive and often fatal condition. This approval follows the presentation of compelling data at the American Heart Association (AHA) Scientific Sessions 2024 and positive results from the ATTRibute-CM Phase 3 trial.
ATTRibute-CM Trial Results
The approval of acoramidis, a near-complete TTR stabilizer, is based on the ATTRibute-CM Phase 3 study, which compared acoramidis with placebo in patients with symptomatic ATTR-CM. The trial met its primary endpoint, a four-component composite endpoint of all-cause mortality, cardiovascular-related hospitalization, NT-proBNP, and 6-minute walk distance, with a win ratio of 1.8 (p<0.0001).
The study found a relative risk reduction of 33.7% in all cardiac mortality. The risk of first cardiovascular hospitalization has a relative risk reduction of 41%. At 42 months, the relative risk reduction of combined cardiac mortality and cardiovascular hospitalizations was 48%.
Sustained Benefits with Long-Term Use
Data from an open-label extension (OLE) study, presented at the AHA Scientific Sessions 2024, highlighted that early initiation and continuous use of acoramidis over 42 months was associated with sustained clinical benefits. Patients who received continuous acoramidis had significantly reduced risks of all-cause mortality (ACM), first cardiovascular hospitalization (CVH), ACM or first CVH, or ACM or recurrent CVH compared with those who were randomized to placebo and moved to acoramidis after the ATTRibute-CM trial.
Compared with the placebo to acoramidis group, continuous acoramidis reduced the risk of ACM alone by a relative risk reduction (RRR) of 33.7% (HR, 0.64; 95% CI, 0.47-0.88; P = .006). Also, 31.5% of participants in the continuous acoramidis group and 53.5% of those in the placebo to acoramidis group reported CVH events through M42, corresponding to a 41.0% RRR with continuous acoramidis (HR, 0.53; 95% CI, 0.41-0.69; P < .0001).
At M42, ACM or first CVH was reported in 42.5% of the continuous acoramidis group and 64.4% of the placebo to acoramidis group, corresponding to a 33.9% RRR in those continuously taking acoramidis (HR, 0.57; 95% CI, 0.46-0.72; P < .0001).
Clinical Implications and Expert Commentary
"Encouraging data suggests Attruby reduces all-cause mortality and cardiovascular hospitalization as early as 3 months after initiation of therapy," said Martha Grogan, MD, FACC, in a BridgeBio press release. "With continued advances in therapy, this previously fatal disease is becoming a manageable chronic cardiovascular condition."
The availability of acoramidis offers a new option for both wild-type and hereditary forms of ATTR-CM, potentially improving patient outcomes and providing greater flexibility for healthcare providers. The drug is a selective TTR stabilizer for the treatment of patients with ATTR-CM that achieves near-complete TTR stabilization in more than 90% of patients.
Addressing Unmet Needs in ATTR-CM
ATTR-CM is characterized by the buildup of amyloid deposits in the heart, leading to heart failure and other cardiac complications. The condition is often underdiagnosed, and until recently, treatment options were limited. The approval of tafamidis in 2019 marked a turning point, and the addition of acoramidis further expands the therapeutic landscape.
With the increasing availability of noninvasive diagnostic tools and expanding therapeutic options, the management of cardiac amyloidosis is transforming, allowing for earlier intervention and improved patient outcomes.
