FDA Accepts NDA Submission for Acoramidis in ATTR-CM

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The FDA's acceptance of the NDA for acoramidis in ATTR-CM was announced on February 05, 2024 and assigns a November 2024 PDUFA for the agent.

US FDA logo in black over a white background. | Credit: US Food and Drug Administration

Credit: US Food and Drug Administration

The US Food and Drug Administration has accepted a New Drug Application (NDA) for acoramidis for the treatment of transthyretin amyloid cardiomyopathy (ATTR-CM) and set a Prescription Drug User Fee Act (PDUFA) action date of November 29, 2024, according to a release from BridgeBio Pharma Incorporated.

Announced in a release from BridgeBio on February 05, 2024, the company’s application is based on data from the phase 3 ATTRibute-CM trial and there are no plans for the FDA to hold an advisory committee meeting to discuss the application at this time.1

“As part of our mission, we seek to improve the lives of patients with amyloidosis by providing support to them and their caregivers throughout their journey. There is a need for more treatment options that can help fill the significant unmet need that exists for patients today. We are excited by BridgeBio’s recent NDA acceptance from the FDA, which we hope moves us one step closer to having acoramidis available as a treatment for the ATTR-CM community,” said Isabelle Lousada, president and CEO of the Amyloidosis Research Consortium.1

A chronic disease characterized by the accumulation of transthyretin fibrils in the myocardium, ATTR-CM represents a significant threat to the longevity and quality of life of patients as well as one of the more unrecognized causes of heart failure. BridgeBio bills Acoramidis as a next-generation, orally-administered, highly potent, small molecule stabilizer of transthyretin and has been shown to lead to stabilization of 90% or more across the dosing interval in previous data.1

The phase 3 ATTRibute-CM trial, which serves as the basis of NDA from BridgeBio, was a double-blind, placebo-controlled trial launched in 2019 with the intent of exploring the safety and efficacy of acoramidis in adult patients with ATTR-CM over the course of 30 months. Randomizing patients in a 2:1 ratio to either acoramidis hydrochloride at a dose of 800 mg twice daily or matching placebo, the trial had a 4-step primary hierarchical analysis as the primary outcome of interest. This analysis included death from any cause, cumulative frequency of cardiovascular-related hospitalization, change in baseline NY-proBNP level, and change in 6-minute walking distance.2

A total of 632 patients underwent randomization in the trial. The cohort had a mean age of 77.6 (Standard deviation [SD], 6.6) years, 90.2% were men, and 90.3% had wild-type TTR.2

Per the trial’s design, ATTRibute-CM included an embedded readout at 12 months. In this readout’s primary analysis, which focused on 6-minute walking distance, results suggested there was no statistical significance between the acoramidis and placebo arms. Specifically, the least-squares mean change in 6-minute walking distance was −26.51 meters (95% confidence interval [CI], −37.07 to −15.96) in the acoramidis group and −24.54 meters (95% CI, −37.26 to −11.83) in the placebo group. In contrast, the 12-month KCCQ-OS score demonstrated a least-squares mean change from baseline of −7.00 (95% CI, −9.65 to −4.34) in the acoramidis group and −10.21 (95% CI, −13.45 to −6.96) in the placebo group.2

Blinding of the trial continued until the 30-month readout. At 30 months, the primary analysis favored acoramidis relative to placebo, with a win ratio of 1.8 (95% CI, 1.4 to 2.2; P <.001) and 63.7% of pairwise comparisons favoring acoramidis compared to 35.9% favoring placebo. Further analysis indicated death from any cause and cardiovascular-related hospitalization contributed more than half the wins and losses to the win ratio (58% of all pairwise comparisons) while NT-proBNP pairwise comparisons yielded the highest ratio of wins to losses (23.3% vs 7.0%).2

Since the initial presentation of results at the European Society of Cardiology Congress 2023, additional data from the trial has been presented at the Heart Failure Society of America and American Heart Association annual scientific sessions. At HFSA, Ahmad Masri, MD, MS, presented data from the 4-year update of the phase 2 trial’s open-label extension program, which found acoramidis was generally well-tolerated and the observed adverse events were consistent with disease severity, concurrent illness, and/or age. At AHA, Masri presented data from a survival analysis from the ATTRibute-CM trial, which assessed the effect of acoramidis on a composite endpoint of all-cause mortality and cardiovascular hospitalization and found such an event occurred among 35.9% of the acoramidis cohort and 50.5% of the placebo cohort, which corresponds to absolute and relative risk reductions of 13.6% and 36%, respectively.3,4

“The FDA’s acceptance of our NDA submission for review reinforces our belief in acoramidis and its potential to make an important contribution to the care of patients with ATTR-CM,” said Jonathan Fox, MD, PhD, president and chief medical officer of BridgeBio Cardiorenal.1 “We look forward to the upcoming review process and the potential for approval in the United States. Similarly, with the European Marketing Authorization Application accepted and with plans to extend our submissions to other countries and regions, we are committed to making acoramidis available to patients.”

References:

  1. BridgeBio Pharma. Bridgebio Pharma announces U.S. Food and Drug Administration (FDA) acceptance of New Drug Application (NDA) for ACORAMIDIS for the treatment of patients with transthyretin amyloid cardiomyopathy (ATTR-cm). BridgeBio Pharma. February 5, 2024. Accessed February 5, 2024. https://investor.bridgebio.com/news-releases/news-release-details/bridgebio-pharma-announces-us-food-and-drug-administration-fda.
  2. Gillmore JD, Judge DP, Cappelli F, et al. Efficacy and Safety of Acoramidis in Transthyretin Amyloid Cardiomyopathy. N Engl J Med. 2024;390(2):132-142. doi:10.1056/NEJMoa2305434
  3. Campbell P. Breaking down Acoramidis Ole Data from HFSA 2023, with Ahmad Masri, MD, MS. HCP Live. October 11, 2023. Accessed February 5, 2024. https://www.hcplive.com/view/breaking-down-acoramidis-ole-data-from-hfsa-2023-with-ahmad-masri-md-ms.
  4. Campbell P. AHA 2023 data highlights potential of Acoramidis in attr-cm. HCP Live. November 16, 2023. Accessed February 5, 2024. https://www.hcplive.com/view/aha-2023-data-highlights-potential-of-acoramidis-in-attr-cm.
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