FDA Approves Acoramidis for ATTR-CM

The FDA has approved acoramidis (Attruby), an oral, near-complete stabilizer of transthyretin indicated for use in adults with transthyretin amyloid cardiomyopathy (ATTR-CM) to reduce cardiovascular death and cardiovascular-related hospitalization.¹

This approval marks the availability of the first near-complete stabilizer of transthyretin. | Image credit: HENADZY - stock.adobe.com

This is the first and only FDA approved therapy that specifies near-complete TTR stabilization (≥90%). According to a news release from manufacturer BridgeBio, acoramidis “was designed to mimic a naturally occurring ‘rescue mutation’ of the TTR gene”—T119M—targeting destabilization of the native TTR tetramer, the root cause of ATTR-CM.

Approval was based on results of the double-blind, phase 3 ATTRibute-CM clinical trial (NCT03860935). Participants (n=632) with symptomatic ATTR-CM were randomly assigned 2:1 to receive either 800 mg acoramidis twice daily (n=421) or placebo (n=211) for 30 months. Mean patient age was 77±6.6 years (90.2% men), and 90.3% had wild-type TTE. Most participants had New York Heart Association class II or class III symptoms.

Analysis included death from any cause, cardiovascular-related hospitalization, change in baseline of N-terminal pro–B-type natriuretic peptide (NT-proBNP) level, and change from baseline in 6-minute walk distance (6MWD). According to study results published in the New England Journal of Medicine,² patients in the acoramidis group demonstrated better outcomes in all 4 primary outcomes, with pairwise comparisons of NT-proBNP showing the highest win ratio vs placebo. Additionally, acoramidis demonstrated a statistically significant treatment effect at 30 months follow-up based on the Kansas City Cardiomyopathy Questionnaire and 6MWD tests.

READ MORE: Outcomes in Transthyretin Amyloid Cardiomyopathy, Examined

Reported adverse events included diarrhea and upper abdominal pain. The majority of these events were mild and resolved without treatment discontinuation.

Results of an ongoing open-label extension study, presented at the American Heart Association Scientific Sessions and simultaneously published in Circulation, suggest that the early initiation and continuous use of acoramidis to treat ATTR-CM through 42 months is associated with sustained clinical benefits,³ including statistically significant reducions in time to first cardiovascular hospitalization or all-cause mortality.

“Transthyretin cardiac amyloidosis is a progressive disease with a poor prognosis when left untreated. Having a new first line treatment option which provides excellent TTR stabilization and improves outcomes in this disease gives patients more options,” said Martha Grogan, MD, a cardiologist and internist at the Mayo Clinic and investigator on the ATTRibute-CM study. “Encouraging data suggests [acoramidis] reduces all-cause mortality and cardiovascular hospitalization as early as three months after initiation of therapy. With continued advances in therapy, this previously fatal disease is becoming a manageable chronic cardiovascular condition.”

The Amyloidosis Support Groups, a nonprofit supporting amyloidosis patients and caregivers, also applauded the FDA’s decision.

“We are excited to be part of the celebration for the FDA approval of [acoramidis],” said Muriel Finkel, Amyloidosis Support Groups president. “The need for more treatment options for patients living with ATTR-CM is crucial to achieving the goal of better outcomes and improved quality of life. Access to this new therapy means more hope and more opportunity to improve the lives of patients with amyloidosis.”

Data on the prevalence of ATTR-CM is challenging to estimate, given missed and delayed diagnoses due to both heterogenous clinical presentation and “previously lacking sensitive diagnostic modality.” Recent advances in nuclear cardiac imaging have made it easier to diagnose ATTR-CM without cardiac biopsy, resulting in more patients being screened for and diagnosed with the disease. Between 5000 and 7000 new cases are identified on an annual basis.⁴

READ MORE: Cardiovascular Resource Center

References

1. Attruby (acoramidis), a near complete TTR stabilizer (≥90%) approved by FDA to reduce cardiovascular death and cardiovascular-related hospitalization in ATTR-CM patients. News release. BridgeBio. November 22, 2024. Accessed November 25, 2024. https://bridgebio.com/news/attruby-acoramidis-a-near-complete-ttr-stabilizer-%E2%89%A590-approved-by-fda-to-reduce-cardiovascular-death-and-cardiovascular-related-hospitalization-in-attr-cm-patients/

2. Gillmore JD, Judge DP, Cappelli F, et al; for the ATTRibute-CM Investigators. Efficacy and safety of acoramidis in transthyretin amyloid cardiomyopathy. N Engl J Med. 2024;390:132-142. doi:10.1056/NEJMoa2305434

3. Biscaldi L. Acoramidis demonstrates sustained clinical benefits in ATTR-CM. Drug Topics. November 18, 2024. Accessed November 25, 2024. https://www.drugtopics.com/view/acoramidis-demonstrates-sustained-clinical-benefits-in-attr-cm

4. Anubhav J, Zahra F. Transthyretin amyloid cardiomyopathy (ATTR-CM). Stat Pearls Publishing. Updated April 27, 2023. Accessed November 25, 2024. https://www.ncbi.nlm.nih.gov/books/NBK574531/