Acoramidis Sustains Benefits in Patients With ATTR-CM in Open-Label Extension Study

Data presented at the 2024 American Heart Association (AHA) Scientific Sessions highlighted that early initiation and continuous use of acoramidis (Attruby; BridgeBio Pharma), a transthyretin (TTR) stabilizer, over 42 months was associated with sustained clinical benefits among adult patients with TTR amyloid cardiomyopathy (ATTR-CM).¹

In the phase 3 ATTRibute-CM trial (NCT03860935), the randomized controlled study that evaluated the safety and efficacy of acoramidis in adult patients with ATTR-CM, acoramidis demonstrated a 42% reduction in composite all-cause mortality (ACM) and recurrent cardiovascular-related hospitalization (CVH) events compared with placebo at 30 months (M30).

Continuous treatment with acoramidis (Attruby; BridgeBio Pharma) in an open-label extension (OLE) study significantly reduced the risk of all-cause mortality (ACM) and cardiovascular-related hospitalizations (CVH) in patients with transthyretin amyloid cardiomyopathy (ATTR-CM). | Image Credit: Jiva Core - stock.adobe.com

Those who completed the trial were invited to enroll in an open-label extension (OLE) study. The researchers continued to give 800 mg of acoramidis twice daily to patients who received it during the previous trial (continuous acoramidis) and switched those who received placebo to acoramidis (placebo to acoramidis).

The primary endpoint through 42 months (M42) was long-term safety and tolerability. Secondary endpoints included time to event for ACM or first CVH, ACM alone, first CVH alone, and ACM or recurrent CVH. Of the 632 participants enrolled in the phase 3 ATTRibute-CM trial, 438 completed treatment. Among these, 389 enrolled in the ongoing OLE, with 263 in the continuous acoramidis group and 126 in the placebo to acoramidis group.

“...patients who received continuous acoramidis for 42 months had significantly reduced risks of ACM, first CVH, ACM or first CVH, or ACM or recurrent CVH compared with those who were randomized to placebo and moved to acoramidis after ATTRibute-CM," Daniel P. Judge, MD, lead investigator, said during his presentation of the data at the 2024 AHA Scientific Sessions.

Compared with the placebo to acoramidis group, continuous acoramidis reduced the risk of ACM alone by a relative risk reduction [RRR] of 33.7% (HR, 0.64; 95% CI, 0.47-0.88; P = .006). Also, 31.5% of participants in the continuous acoramidis group and 53.5% of those in the placebo to acoramidis group reported CVH events through M42, corresponding to a 41.0% RRR with continuous acoramidis (HR, 0.53; 95% CI, 0.41-0.69; P < .0001).

At M42, ACM or first CVH was reported in 42.5% of the continuous acoramidis group and 64.4% of the placebo to acoramidis group, corresponding to a 33.9% RRR in those continuously taking acoramidis (HR, 0.57; 95% CI, 0.46-0.72; P < .0001).

Overall, continuous acoramidis treatment resulted in a 48.2% reduction in the relative risk of ACM or recurrent CVH through M42 compared with the placebo to acoramidis group (relative risk ratio, 0.52; 95% CI, 0.39-0.68; P < .0001). Judge noted that no new clinically important safety issues were identified in this long-term evaluation.

Lastly, he acknowledged the study’s limitations, including the lack of a true control arm; this is the natural restriction of all OLE trials. Also, patients who chose to stay on or switch to tafamidis rather than enroll in the OLE were excluded. Despite these limitations, he expressed confidence in his study’s findings.

“Continuous acoramidis efficacy data up to 42 months now underscore the importance, and this is true of all therapies, of early diagnosis and prompt initiation of treatment to improve outcomes in ATTR-CM,” Judge said.

On November 22, 2024, just 4 days after the conclusion of the 2024 AHA Scientific Sessions, the FDA approved acoramidis for the treatment of adults with ATTR-CM²; this made it the first and only approved product with a label specifying near-complete stabilization of TTR. The agency made this decision 1 week before the assigned Prescription Drug User Fee Act (PDUFA) action date of November 29, set after BridgeBio’s New Drug Application was accepted in February.

“Having a new first-line treatment option which provides excellent TTR stabilization and improves outcomes in this disease gives patients more options,” Martha Grogan, MD, of the Mayo Clinic said in a press release.³ “Encouraging data suggest Attruby reduces all-cause mortality and cardiovascular hospitalization as early as 3 months after initiation of therapy. With continued advances in therapy, this previously fatal disease is becoming a manageable chronic cardiovascular condition.”

References

1. Judge DP, Gillmore JD, Alexander KM, et al. Long-term efficacy and safety of acoramidis in ATTR-CM: initial report from the open-label extension of the ATTRibute-CM trial. Circulation. doi:10.1161/circulationaha.124.072771
2. Campbell P. FDA approves acoramidis for ATTR-CM. AJMC. November 25, 2024. Accessed December 5, 2024. https://www.ajmc.com/view/fda-approves-acoramidis-for-attr-cm
3. BridgeBio Pharma. AttrubyTM (acoramidis), a near complete TTR stabilizer (≥90%), approved by FDA to reduce cardiovascular death and cardiovascular-related hospitalization in ATTR-CM patients. BridgeBio Pharma. November 22, 2024. Accessed December 5, 2024. https://investor.bridgebio.com/news-releases/news-release-details/attrubytm-acoramidis-near-complete-ttr-stabilizer-90-approved