Announced on July 17, 30-month data from the ATTRibute-CM trial provide the most comprehensive insight yet into the long-term effects of acoramidis use in patients with transthyretin amyloid cardiomyopathy.
BridgeBio Pharma has announced positive data from their phase 3 study of acoramidis in transthyretin amyloid cardiomyopathy (ATTR-CM), clearing the way for regulatory submission of a New Drug Application (NDA) before the end of 2023.
Announced on July 17, 2023, 30-month data from the ATTRibute-CM study indicate use of the investigational, next-generation, orally-administered, highly potent, small molecule stabilizer of transthyretin was associated with statistically significant improvement in the study’s primary endpoint and an 81% on-treatment survival rate, which correlated to an absolute risk reduction for mortality of 6.43% and a relative risk reduction of 25% compared to placebo therapy.1
“The outstanding results of the ATTRibute-CM study provide new hope to patients living with transthyretin amyloid cardiomyopathy, or ATTR-CM”, said Daniel Judge, MD, professor of Medicine and Cardiology at the Medical University of South Carolina, and co-chair of the ATTRibute-CM Steering Committee.1 “The consistent and clinically meaningful benefits on survival, hospitalization, and additional measures of illness severity are truly remarkable.”
With plans to unveil further 30-month data as a late-breaking presentation annual meeting of the European Society of Cardiology, the phase 3 ATTRibute-CM trial was launched by BridgeBio in 2019 as a 2-part trial with the intent of exploring the safety and efficacy of the agent in patients with wild-type or variant transthyretin ATTR-CM. Part A of the trial was aimed at examining 12-month endpoints and part B examined 30-month endpoints. For inclusion, patients needed to have symptoms meeting criteria for New York Heart Association class I-III heart failure and have an ATTR-positive biopsy or 99mTc scan.1
In December 2021, BridgeBio announced to-line results from part A of the ATTRibute-CM trial, which had a primary endpoint of interest of change in 6-minute walking distance at month 12. Results of the analysis performed for part A of the trial indicated the mean observed decline in 6-minute walking distance at 12 months was 9 meters among those in the acoramidis group and 7 meters among the placebo group, respectively.2
Unlike part A, part B used a hierarchical analysis comparing incidence of all-cause mortality, then frequency of cardiovascular-related hospitalization, then change from baseline in NT-proBNP, then change from baseline in 6-minute walk distance at 30 months as the primary outcome of interest.1
Topline data from part B of the trial suggests use of acoramidis was associated with statistically significant improvement in the primary outcome of interest, with a Win Ratio of 1.8 (P < .0001). The release from BridgeBio highlighted 58% of ties in Finkelstein-Schoenfeld (F-S) primary analysis were broken by all-cause mortality and frequency of cardiovascular-related hospitalization, with statistical significance also achieved on an F-S test with these parameters alone (P=.0182).1
Further analysis evidence of a statistically significant relative risk reduction of 50% (P < .0001) in frequency of cardiovascular-related hospitalization favoring acoramidis as well as an on-treatment survival rate of 81% relative to a 74% rate among placebo users, which the release notes is representative of an absolute risk reduction of 6.43% and relative risk reduction of 25%. Additionally, a statistically significant treatment effect was observed at 30 months for change from baseline in NT-proBNP (P < .0001), change from baseline in KCCQ score (P < .0001), and change from baseline in 6-minute walk distance (P < .0001).1
In their July 17, 2023 release, BridgeBio also called attention to trial protocol allowing tafamadis drop-in after at least 12 months among patients in either arm. Examined in a posthoc fashion, this analysis revealed acoramidis showed a 42% greater increase in serum transthyretin levels relative to tafamidis and a 92% improvement in median NT-proBNP relative to tafamadis and placebo therapy.1
“Our heartfelt thanks go out to the patients, their caregivers, investigators, and study staff who have actively participated in ATTRibute-CM and continue to contribute to this pivotal research," stated Jonathan Fox, MD, PhD, resident and chief medical officer of BridgeBio Cardiorenal.1 "We are extremely encouraged by the robustly positive and consistent findings of the ATTRibute-CM study, which confirm our position that highly potent TTR stabilization has the potential to profoundly impact patients’ lives. We look forward to presenting the data to health authorities to bring acoramidis to patients as expeditiously as possible."