Phase 3 Findings Support Acoramidis as Potential Therapy for Transthyretin Amyloid Cardiomyopathy
Based on the positive findings, the company intends to submit a new drug application to the FDA before the end of 2023, with regulatory filings in additional markets to follow in 2024.
Daniel Judge, MD
Recently reported findings from the phase 3 ATTRibute-CM study (NCT03860935) showed that acoramidis (BridgeBio), an investigational small molecule stabilizer of transthyretin (TTR), was effective in the treatment of TTR amyloid cardiomyopathy (ATTR-CM). BridgeBio plans on submitting a new drug application to the FDA by the end of this year, with potential additional regulatory filings in other markets following that in 2024.
All told, data from the double-blind, placebo-controlled study showed that acoramidis achieved a statistically significant improvement in the primary end point, demonstrated by a win ratio of 1.8 (P <.0001). Comprised of 632 individuals with an established diagnosis of ATTR-CM with either wild-type TTR or variant TTR genotype, the study’s primary end point was a hierarchical combination of all-cause mortality, cumulative frequency of cardiovascular-related hospitalization, change from baseline in N-terminal prohormone of brain natriuretic peptide (NT-proBNP), and change from baseline in 6-minute walk test, over a 30-month fixed treatment duration.
"The outstanding results of the ATTRibute-CM study provide new hope to patients living with transthyretin amyloid cardiomyopathy, or ATTR-CM,” Daniel Judge, MD, professor of medicine and cardiology at the Medical University of South Carolina, and co-chair of the ATTRibute-CM steering committee, said in a statement.1 "The consistent and clinically meaningful benefits on survival, hospitalization, and additional measures of illness severity are truly remarkable."
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In addition to the promising results on the primary end point, acoramidis-treated patients had a 81% survival rate compared with rates of 74% for those on placebo, equating to an absolute risk reduction of 6.43% and relative risk reduction of 25%. Frequency of cardiovascular-related hospitalization, a secondary endpoint, was reduced by 50% among treated individuals (P <.0001). In terms of safety, no new signals of potential clinical concern were identified.
At 30 months, investigators observed statistically significant treatment effects across each of the individual measured markers of morbidity, quality of life, and function. These included change in NT-proBNP (P <.0001), change in Kansas City Cardiomyopathy Questionnaire (P <.0001), and change in 6MWT (P <.0001).
The allowance of tafamidis drop-in, a TTR stabilizer, after 12 months in both arms of the trial allowed BridgeBio to conduct a post-hoc analysis assessing the differences in stabilizer performance. Although a small sample size, findings at 30 months showed a 42% greater increase in serum TTR levels vs tafamidis and a 92% improvement in median NT-proBNP relative to placebo and tafamidis, further strengthening acoramidis’ efficacy profile. The company did note that these were exploratory analyses, and that inferences can’t be made on the potential effectiveness or safety of acoramidis and tafamidis.
"Our heartfelt thanks go out to the patients, their caregivers, investigators, and study staff who have actively participated in ATTRibute-CM and continue to contribute to this pivotal research," Jonathan Fox, MD, PhD, president and chief medical officer at BridgeBio Cardiorenal, said in a statement.1 "We are extremely encouraged by the robustly positive and consistent findings of the ATTRibute-CM study, which confirm our position that highly potent TTR stabilization has the potential to profoundly impact patients’ lives. We look forward to presenting the data to health authorities to bring acoramidis to patients as expeditiously as possible."
