BridgeBio presents results from Phase 3 ATTRibute-CM study of acoramidis

BridgeBio Pharma announced the presentation of detailed results from its Phase 3 ATTRibute-CM study of acoramidis for patients with ATTR-CM. A highly statistically significant result, demonstrated by a Win Ratio of 1.8, was observed on the primary endpoint. This result was consistent across both variant and wild-type ATTR-CM patients, as well as across NYHA Class I, II and III patients. Other key results from the study at Month 30 included: An 81% survival rate on acoramidis for an absolute risk reduction of 6.4% and a relative risk reduction of 25%, despite a ~50% higher rate of tafamidis use on the placebo arm relative to the treatment arm; The on-treatment 81% survival rate, the highest observed rate in a controlled, prospective study of ATTR-CM patients to the company’s knowledge, approaches the survival rate in the age-matched US database. Of note, overall 79% of deaths in the study were cardiovascular in nature, and the results for CV-related mortality were consistent with what was observed on ACM. The treatment group experienced a 14.9% CV-related mortality rate versus a 21.3% CV-related mortality rate in the placebo group, for a relative risk reduction of 30% on CV-related mortality. A highly statistically significant relative risk reduction of 50% on frequency of CVH. The 0.29 mean annual CVH frequency on acoramidis approaches the annual hospitalization rate observed in the broader US Medicare population. A highly statistically significant treatment effect at 30 months on change from baseline in each of NT-proBNP, KCCQ, and 6MWD. A higher proportion of individuals experienced a reduction in NT-proBNP on acoramidis relative to placebo. A higher proportion of individuals experienced an increase in 6MWD on acoramidis relative to placebo. To the company’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 tafamidis, independent of TTR genotype. Serum TTR was promptly and consistently elevated throughout the study in patients receiving acoramidis. In an exploratory post-hoc analysis of the relationship between on-treatment serum TTR levels and on-treatment measures of CVH, NT-proBNP, and KCCQ, there appears to be an association between the mean on-treatment TTR level and each of these three variables. In a comparative exploratory post hoc analysis enabled by tafamidis drop-in, albeit at low patient numbers, acoramidis showed a 42% greater increase in serum TTR levels relative to placebo + tafamidis. Acoramidis was generally well-tolerated with no safety findings of potential clinical concern. The company intends to submit its NDA to the US FDA before the end of 2023, with regulatory filings in additional markets to follow in 2024. Acoramidis has intellectual property protection out to at least 2039.