Phase 3 data show acoramidis improves outcomes in transthyretin amyloid cardiomyopathy
Key takeaways:
- Acoramidis reduced risk for all-cause mortality and CV-related hospitalizations in symptomatic transthyretin amyloid cardiomyopathy.
- Researchers noted improvements in functional and quality-of-life measures.
Acoramidis, a treatment for symptomatic transthyretin amyloid cardiomyopathy, was associated with marked improvements in all-cause mortality and CV-related hospitalizations compared with placebo, according to a press release from BridgeBio.
The phase 3 ATTRibute-CM study of acoramidis in transthyretin amyloid cardiomyopathy, or ATTR-CM, was designed to study the drug’s efficacy and safety. Researchers enrolled 632 participants with symptomatic hereditary or wild-type ATTR-CM and NYHA class I, II or III HF.
Acoramidis is an investigational, next-generation, small molecule stabilizer of transthyretin (TTR).
“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 the release. “The consistent and clinically meaningful benefits on survival, hospitalization, and additional measures of illness severity are truly remarkable.”
Key results from the clinical trial include:
- Improvement in the primary endpoint, which was a hierarchical analysis prioritizing all-cause mortality, then frequency of CV-related hospitalization, then change from baseline in N-terminal pro-B type natriuretic peptide level, and then change from baseline in 6-minute walk distance, demonstrated by a win ratio of 1.8 (P < .0001).
- An 81% on-treatment survival rate vs. a 74% survival rate among patients assigned placebo, which according to the release begins to approach actuarial models of life expectancy absent ATTR-CM. The absolute risk reduction was 6.43% and the relative risk reduction was 25%
- A relative risk reduction of 50% (P < .0001) in frequency of CV-related hospitalizations. The impact and marked magnitude of risk reduction was seen across all analytical methods employed.
In the release, the company also noted a statistically significant treatment effect at 30 months across additional measured markers of morbidity, quality of life and function, including change from baseline in NT-proBNP level (P < .0001); change from baseline in Kansas City Cardiomyopathy Questionnaire score (P < .0001) and change from baseline in 6-minute walk distance (P < .0001). Researchers did not report any safety signals of clinical concern.
Additionally, the allowance of tafamidis (Vyndamax, Pfizer) drop-in after at least 12 months for the placebo and the acoramidis arms in ATTRibute-CM trial provided an opportunity to analyze, in an exploratory post hoc fashion, differences in stabilizer performance as measured by serum TTR and NT-proBNP, the company stated in the release. In those analyses, 30-month findings demonstrated that acoramidis showed a 42% greater increase in serum TTR levels vs. tafamidis and acoramidis showed a 92% improvement in median NT-proBNP relative to placebo and tafamidis.
“ATTR-CM is an increasingly recognized cause of HF,” Muriel Finkel, president of the non-profit organization Amyloidosis Support Groups, said in the release. “The results from BridgeBios ATTRibute-CM trial are very exciting and bring much hope to amyloidosis patients and their loved ones.”
The 30-month data follows earlier news, reported by Healio, that the first part of the ATTRibute-CM trial did not meet its primary endpoint. For that part of the study, researchers assessed the 12-month endpoint of change in baseline 6-minute walk distance among patients assigned to acoramidis 800 mg twice daily compared with placebo. Among participants with symptomatic 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). At the time, the ATTRibute-CM independent data monitoring committee, steering committee co-chairs and BridgeBio Pharma agreed that acoramidis may demonstrate benefit if the study was continued to the 30-month endpoint.
"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,” Jonathan Fox, MD, PhD, president and chief medical officer of BridgeBio Cardiorenal, said in the release. “We look forward to presenting the data to health authorities to bring acoramidis to patients as expeditiously as possible.”
In the release, the company stated it intends to submit its NDA to the FDA before the end of 2023, with regulatory filings in additional markets to follow in 2024.
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