Trial of acoramidis for transthyretin amyloid cardiomyopathy misses primary endpoint
In the 12-month topline results of the ATTRibute-CM trial, acoramidis, a treatment for symptomatic transthyretin amyloid cardiomyopathy, did not meet its primary endpoint, BridgeBio Pharma announced.
Among participants with symptomatic transthyretin amyloid cardiomyopathy (ATTR) and baseline estimated glomerular filtration rate of 30 mL/min/1.73m2 or more, the mean decline in 6-minute walk distance at 12 months was similar among those receiving acoramidis compared with placebo (9 m vs. 7 m; P = .76).
“This result is disappointing and baffling. I am, along with many others, searching for answers regarding the [6-minute walk distance],” Neil Kumar, PhD, founder and CEO of BridgeBio, said in the release. “The results do not appear to be due to a baseline imbalance. The hypotheses we are currently evaluating include context bias, training bias and an evolution in diagnosis and standard of care. The drug does appear to be pharmacologically active and well-tolerated, and we observed improvement on quality of life with promising trends on adverse events leading to death. The drug seems to be doing what we are asking of it. If we observe enough clinical outcome events at Month 30, I am still hopeful that we will demonstrate the benefit of acoramidis treatment.”
For the ATTRibute-CM trial, researchers enrolled 632 participants with symptomatic hereditary or wild-type transthyretin amyloid cardiomyopathy and NYHA class I, II or III.
According to the release, ATTRibute-CM is a two-part study with 12-month endpoint of change in baseline 6-minute walk distance among patients assigned to acoramidis 800 mg twice daily compared with placebo. The second half of the study will assess a 30-month endpoint of change in all-cause death and CV hospitalizations between the two groups.
The ATTRibute-CM independent data monitoring committee, steering committee co-chairs and BridgeBio Pharma agreed that acoramidis may demonstrate benefit if the study is continued to the 30-month endpoint.
ATTRibute-CM enrolled a similar patient population as the prior ATTR-ACT trial of tafamidis (Vyndamax, Pfizer).
As Healio previously reported, tafamidis lowered risk for all-cause mortality and CV-related hospitalizations among patients with hereditary and wild-type transthyretin amyloid cardiomyopathy.
According to the release, other findings from the 12-month results of ATTRibute-CM included:
- improved Kansas City Cardiomyopathy Questionnaire Overall Summary Score in the acoramidis arm compared with placebo (P < .05);
- improved median N-terminal pro-B type natriuretic peptide levels in the acoramidis arm compared with placebo (P < .05);
- increased serum transthyretin concentration, a measure of transthyretin stabilization, in the acoramidis arm compared with placebo (P < .01);
- adverse event rates of 91.9% of the acoramidis arm and 85.3% of the placebo arm;
- serious adverse events rates of 20.2% of the acoramidis arm and 23.2% of the placebo arm; and
- adverse events resulting in death rates of 4.5% of the acoramidis arm and 6.2% of the placebo arm.
“Although these results were not what we hoped, the most important moment in this trial will be the Part B readout at 30 months, where we will see the effects of acoramidis on all-cause mortality and cardiovascular hospitalizations. From what I’ve seen so far, I remain enthusiastic about getting to that endpoint,” Daniel Judge, MD, professor in the division of cardiology at the Medical University of South Carolina, and co-chair of the ATTRibute-CM Steering Committee, said in the release.
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