RARE Daily

BridgeBio’s Presents Positive Late Stage Acoramidis Data Supporting Previously Disclosed Success in ATTR-CM

August 28, 2023

Rare Daily Staff

BridgeBio Pharma presented detailed positive results from its phase 3 ATTRibute-CM study of acoramidis for patients with transthyretin amyloid cardiomyopathy, or ATTR-CM, a buildup of faulty proteins on the heart that can cause heart failure.

The results were presented at the European Society of Cardiology Congress 2023, and supported previously reported positive results in July.

A highly statistically significant result was observed on the primary endpoint, a hierarchical analysis prioritizing in order: all-cause mortality, then frequency of cardiovascular-related hospitalization, then change from baseline in NT-proBNP, then change from baseline in six-minute walk distance. This result was consistent across both variant and wild-type ATTR-CM patients, as well as across New York Heart Association Class I, II and III patients.

There was an 81 percent on-treatment survival rate (versus a 74 percent survival rate on placebo), which begins to approach actuarial models of life expectancy absent ATTR-CM of 85 percent in this population. The absolute risk reduction was 6.43 percent and the relative risk reduction was 25 percent.

Results also showed a highly statistically significant relative risk reduction of 50 percent on frequency of cardiovascular-related hospitalization. The impact and marked magnitude of risk reduction was seen across all analytical methods employed.

The company consistently observed a statistically significant treatment effect at 30 months across additional measured markers of morbidity, quality of life, and function: change from baseline in N-terminal prohormone of brain natriuretic peptide (NT-proBNP); change from baseline in Kansas City Cardiomyopathy Questionnaire; and change from baseline in 6-minute walk distance. To BridgeBio’s knowledge, these on-treatment proportions of improving patients are higher than have been observed in prior controlled studies of ATTR-CM.

As measured by ex vivo assays of TTR stabilization, acoramidis achieved a greater degree of TTR stabilization as compared to clinically relevant concentrations of the standard of care treatment tafamidis, independent of TTR genotype.

Acoramidis was generally well-tolerated with no safety findings of potential clinical concern.

“The consistently positive results of ATTRibute-CM, from the primary endpoint and its components to secondary endpoints of mortality, morbidity, physical function, and quality of life, further substantiate our hypothesis that highly potent TTR stabilization has the potential to deliver differential benefits to patients,” said Jonathan Fox, president and chief medical officer of BridgeBio Cardiorenal. “In particular, we observed absolute survival and hospitalization rates approaching those of similarly aged populations not afflicted with ATTR-CM.”

He noted that 45 percent of completers displayed improvement from baseline in NT-proBNP, and 40 percent walked farther in six minutes at study end compared to baseline, are to me remarkable observations in a cohort with a disease commonly described as relentlessly progressive. The prompt and sustained observed increase in serum TTR, an in vivo reflection of increased stabilization, serves to further strengthen the relationship between measures of acoramidis’ ability to avidly bind and stabilize TTR and the read-through to robust clinical benefits for patients with ATTR-CM.”

The company intends to submit its NDA to the U.S. Food and Drug Administration before the end of 2023, with regulatory filings in additional markets to follow in 2024.

Photo: Jonathan Fox, president and chief medical officer of BridgeBio Cardiorenal

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