Acoramidis Demonstrates Sustained Clinical Benefits in ATTR-CM
A PDUFA date for acoramidis has been set for November 29, 2024.
Results of an ongoing open-label extension study suggest that early initiation and continuous use of acoramidis to treat transthyretin amyloid cardiomyopathy (ATTR-CM) through 42 months is associated with sustained clinical benefits, according to research published at the American Heart Association (AHA) Scientific Sessions and simultaneously published in Circulation.1,2
A PDUFA date for acoramidis has been set for November 29, 2024. | Image credit: janya - stock.adobe.com
Participants who successfully completed the phase 3 ATTRibute-CM study (NCT03860935) were invited to enroll in the current open-label extension. For the extension study, those who had previously received acoramidis continued this treatment, while those who had received placebo were switched to acroamidis therapy. Individuals who had received concomitant tafamidis were required to discontinue that medication in order to participate in the extension trial.
The primary clinical efficacy outcomes included time to event for all-cause mortality or the first cardiovascular-related hospitalization, all-cause mortality alone, first cardiovascular hospitalization alone, and all-cause mortality or recurrent cardiovascular hospitalization. Biomarker, functional assessment, and quality of life metrics included change from baseline in N-terminal pro-B-type natriuretic peptide (NT-proBNP), 6-minute walk distance (6MWD), serum transthyretin, and Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS) score.
The open-label extension trial cohort included 389 of the 438 participants who successfully completed the ATTRibute-CM study (263 on continuous acoramidis and 126 who switched from placebo).
Initial results presented at AHA showed that continuous acoramidis treatment was associated with a sustained improvement relative to placebo in time to first cardiovascular hospitalization or all-cause mortality, starting at month 3 of the ATTRibute-CM trial; statistically significant 36% and 34% reductions in all-cause mortality by months 36 and 42, respectively; significant reductions of composite all-cause mortality and cardiovascular hospitalizations by 46% and 48% at months 36 and 42, respectively; and evidence of early benefit in patients who crossed over from placebo to treatment at month 30. Study data also indicated that acoramidis therapy continues to be well-tolerated.
READ MORE: Outcomes in Transthyretin Amyloid Cardiomyopathy Examined
“Results from the ATTRibute-CM [open-label extension] continue to showcase the potential of acoramidis, with ongoing data across the study suggesting that early intervention with this stabilizer leads to early separation from placebo, with sustained benefits for patients with ATTR-CM,” said Daniel Judge, MD, professor of medicine and cardiology at the Medical University of South Carolina, in a news release. Judge presented the data at AHA.
Investigators also found that the early change from baseline NT-proBNP seen in ATTRribute-CM continued in the open-label extension: by month 42, the geometric mean for fold change was 1.10 in the continuous treatment group and 2.29 in the placebo to acoramidis group. Early increase in serum transthyretin was sustained, with a mean change from baseline of 9.1 mg/dL at month 30 and 8.9 mg/dL at month 31. In the placebo to acroamidis group, this change was 1.3 mg/dL and 7.4 mg/dL at months 30 and 31, respectively.
Additionally, quality of life, evaluated by KCCQ-OS score, was “well preserved.”
“We are pleased to share the initial results from the ongoing open-label extension study of ATTRibute-CM, which showcase the sustained benefits of acoramidis treatment for patients with ATTR-CM,” said Jonathan Fox, MD, PhD, chief medical officer of BridgeBio Cardiorenal. “Coupled with acoramidis’ earliest time to separation of any known ATTR-CM treatment on clinical outcomes at 3 months, these analyses continue to support acoramidis as a meaningful first line option.”
A New Drug Application has been submitted to the FDA based on positive results of the ATTRibute-CM clinical trial. The assigned PDUFA date is November 29, 2024.
READ MORE: Cardiology Resource Center
