BridgeBio Pharma reports month 12 topline results from phase III ATTRibute-CM Study for acoramidis to treat ATTR-CM.

The mean observed decline in 6MWD at Month 12 in participants receiving acoramidis or placebo with baseline eGFR ? 30 mL/min/1.73m2 were 9 meters and 7 meters, respectively. Decline observed in both arms of ATTRibute-CM was similar to expected functional decline in healthy elderly adults. The declines were also substantially less than the >40 meter annual declines observed in previous untreated arms reviewed by the company. The decline in the ATTRibute-CM placebo group was more than 70% lower than the decline observed in the ATTR-ACT treatment group The ATTRibute-CM independent data monitoring committee recommends continuing the study based on unblinded data reviews. Despite the unexpected performance of the six-minute walk test, the trial’s steering committee co-chairs and the Company agree that there is potential for acoramidis to demonstrate benefit on the Month 30 endpoint which includes all-cause mortality and cardiovascular hospitalizations.

ATTRibute-CM enrolled 632 participants with symptomatic ATTR-CM, associated with either wild-type or variant TTR, with New York Heart Association (NYHA) Class I-III symptoms. The study is designed as a two-part study with Part A (Month 12) comparing change from baseline in 6MWD and Part B (Month 30) utilizing a hierarchical comparison including all-cause mortality and cardiovascular hospitalizations. ATTRibute-CM enrolled a similar patient population as ATTR-ACT, excepting a smaller proportion of U.S. participants and TTR variant carriers. Participants were randomized 2:1 between treatment (acoramidis 800 mg) and placebo twice daily.

Based on data available after 12 months of treatment, the Company observed : i.In the primary analysis, change from baseline in 6MWD was not improved in the acoramidis arm relative to the placebo arm (p = 0.76) a. Key differences in NYHA class, geographic distribution, and TTR variant status compared to the ATTR-ACT population do not appear to have affected the primary outcome of ATTRibute-CM. b. The only participant sub-population the company has reviewed to date that exhibited substantial placebo decline in 6MWD by Month 12 was the variant population. In that population, observed decline in placebo and acoramidis was -40 meters and -2 meters, respectively. ii. Acoramidis improved Kansas City Cardiomyopathy Questionnaire Overall Summary Score relative to placebo (nominal p < 0.05, mixed model repeated measures without imputation). iii.Acoramidis improved NT-proBNP relative to placebo. Median percent change from baseline at Month 12 in acoramidis-treated and placebo-treated participants were +0.6% and +24.3%, respectively (nominal p < 0.05 based on absolute changes from baseline between groups). iv. Acoramidis increased serum TTR levels relative to placebo. Mean percent change from baseline at Month 12 in acoramidis-treated and placebo-treated participants were +38.5% and -0.7%, respectively (nominal p < 0.01 based on absolute changes from baseline between groups) v. Acoramidis was generally well-tolerated with no safety signals of clinical concern identified. To protect the integrity of Part B, the Sponsor’s access to unblinded adverse event data for Part A excludes AEs leading to a cardiovascular hospitalization (as determined by investigators) excepting events with the outcome of death.

Adverse events occurred in 85.3% of placebo-treated participants and 91.9% of acoramidis-treated participants. Serious adverse events occurred in 23.2% of placebo-treated participants and 20.2% of acoramidis-treated participants Adverse events with outcome of death occurred in 6.2% of placebo-treated participants and 4.5% of acoramidis-treated participants .