Image of a heart with a DNA double helix in front of it to indicate cardiovascular disease and the impact of epigenetic aging changes.
Credit: iStock/SvetaP DNA double helix: iStock/Kagenmi

BridgeBio’s candidate therapy for the rare disease transthyretin amyloid cardiomyopathy met its primary endpoint, according to results from a 30-month Phase III trial.

The findings showed 81% of participants taking the drug candidate acoramidis were alive at 30 months versus 74% of the placebo group. The therapy also cut cardiac-related hospitalization rates by 50%.

The treatment also improved other markers including N-terminal prohormone of brain natriuretic peptide (NT-proBNP)—a biomarker of the disease, and improved results of the Kansas City Cardiomyopathy Questionnaire and the six-minute walk distance test.

Transthyretin amyloid cardiomyopathy is a rare genetic condition, with around 5,000 to 7,000 new cases identified in the U.S. each year. It can be inherited, but can also occur spontaneously with aging. It is caused by misfolding of the transthyretin (TTR) protein that occurs due to mutations in the TTR gene.

Transthyretin (transports thyroxine and retinol) is a hormone that transports thyroxine and retinol to the liver. In the mutant form seen in transthyretin amyloid cardiomyopathy, it forms amyloid fibrils that accumulate in the heart and can lead to heart failure in those affected.

Acoramidis works by mimicking a ‘rescue variant’ of the TTR gene shown to prevent or minimize transthyretin amyloidosis in individuals carrying pathogenic, or disease-causing, mutations in this gene.

There is already one drug approved to treat transthyretin amyloid cardiomyopathy, tafamidis, which was developed by Pfizer and approved in 2019. It raised survival in these patients from around 57% to 74% at 30 months.

In the current study, tafamidis drop-in after at least 12 months in both the placebo and the acoramidis arms was allowed. This allowed some comparison between the two drugs and showed that acoramidis showed 42% greater increase in serum TTR levels and a 92% improvement in median NT-proBNP relative to placebo and tafamidis. However, these results cannot be used as an official comparator, as the study was not designed for a head-to-head comparison between the two drugs.

In addition to the positive results from the trial, the investigators also report that no significant side effects were observed in the analysis.

“Transthyretin amyloid cardiomyopathy is an increasingly recognized cause of heart failure. The results from BridgeBio’s ATTRibute-CM trial are very exciting and bring much hope to amyloidosis patients and their loved ones,” said Muriel Finkel, president of amyloidosis support groups, a non-profit organization dedicated to the support of amyloidosis patients and caregivers.

BridgeBio plans to submit a new drug application to the U.S. FDA before the end of 2023, with regulatory filings to follow in a number of markets in 2024.

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