The transthyretin amyloid cardiomyopathy (ATTR-CM) treatment landscape is on the cusp of significant change as BridgeBio's acoramidis potentially enters the market to challenge Pfizer's established tafamidis (Vyndaqel and Vyndamax). The FDA is expected to decide on acoramidis by November 29, marking a pivotal moment for BridgeBio and patients with this rare but severe cardiovascular disease.
Acoramidis: Efficacy and Market Potential
Neil Kumar, CEO of BridgeBio, expressed confidence in acoramidis, highlighting its potential as the company's first "very, very large drug." The ATTR-CM market, valued at $5.2 billion in 2023, is projected to reach $9.4 billion by 2031, underscoring the significant commercial opportunity. Acoramidis, like tafamidis, stabilizes the transthyretin (TTR) tetramer, preventing misfolding and amyloid deposit buildup in the heart. According to a BMO Capital Markets survey of physicians, 40% believe acoramidis is "incrementally better" than tafamidis, while 50% see similar efficacy.
Clinical Trial Data and Mortality Benefit
In the Phase III ATTRibute-CM trial, acoramidis demonstrated an 81% survival rate compared to 74% in the placebo group and halved the relative risk of cardiovascular-related hospitalizations (p<0.05). While the trial met its primary endpoint, it did not achieve statistical significance for the pre-specified secondary endpoint of all-cause mortality (ACM)/cardiovascular mortality (CVM). However, updated analyses from the open-label extension of ATTRibute-CM, presented at the American Heart Association's 2024 Scientific Sessions, showed a statistically significant ACM benefit with acoramidis.
Competition and Emerging Therapies
Despite the promising data, acoramidis faces challenges. Tafamidis has already demonstrated a significant reduction in mortality risk. Moreover, acoramidis requires twice-daily dosing, while tafamidis is administered once daily. RNA therapies are also emerging as potential competitors. Alnylam's Amvuttra (vutrisiran) showed a 28% reduction in the composite of ACM and recurrent CV events in the Phase III HELIOS-B trial. AstraZeneca and Ionis are studying Wainua (eplontersen) for ATTR-CM in the Phase III CARDIO-TTRansform study. Intellia Therapeutics presented Phase I data on nexiguran ziclumeran (nex-z), a gene editor, showing a 90% mean reduction in serum TTR levels at 12 months after a single dose.
Expert Opinions and Market Outlook
Kostas Biliouris, director of biotech equity research at BMO Capital Markets, noted that acoramidis is "probably incrementally better" than tafamidis. William Blair analysts emphasized the importance of demonstrating a reduction in all-cause mortality to gain market share. Mathew Maurer, a professor of cardiology at Columbia University Irving Medical Center, pointed out that while Vyndaqel and Vyndamax slow disease progression, they don't reverse it, highlighting the potential of RNA therapies to stop the production of the mutated TTR protein.
