FDA Grants Approval to BridgeBio for Treatment of Hereditary Cardiomyopathy
BridgeBio, located in California, has achieved a significant milestone with the approval from the US FDA for its primary drug candidate, acoramidis, now branded as Attruby. This medication is aimed at addressing transthyretin amyloid cardiomyopathy (ATTR-CM), a genetic heart disorder.
This recent approval marks a crucial turn in the journey for both BridgeBio and acoramidis. The drug encountered difficulties back in 2021 when it did not show favorable outcomes against placebo in initial phase 3 trial results, resulting in a steep decline in the company’s shares.
Undeterred, BridgeBio noted that the placebo patient group performed better than anticipated, likely reflecting enhancements in patient care. They restructured their phase 3 study and continued pursuing acoramidis, eventually leading to this long-anticipated approval.
The FDA’s endorsement, disclosed on Friday, relies on a phase 3 trial published earlier this year. Results indicated a notable 42% decrease in all-cause mortality and cardiovascular events, alongside a 50% reduction in cumulative cardiovascular events at the 30-month mark compared to placebo.
An open-label extension study further illustrated the drug’s efficacy over extended durations, showcasing respective reductions of 34% and 48% in the same endpoints after 42 months.
While the precise prevalence of ATTR-CM remains ambiguous, recent estimates suggest a higher occurrence than previously understood, rising from 5 in 100,000 individuals in 2004 to 35 per 100,000 in 2022. The disorder arises from abnormal transthyretin protein accumulation in the heart, leading to stiffened heart walls, disrupted heart function, and eventually diastolic dysfunction followed by heart failure.
Acoramidis is designed as an oral small molecule therapy that stabilizes transthyretin by imitating a highly stable variant (T119M) while minimizing amyloid fibril formation and halting disease advancement.
Trial outcomes demonstrated acoramidis’s ability to nearly fully stabilize transthyretin, maintaining its role in transporting thyroxine and vitamin A, while considerably alleviating cardiovascular complications for patients.
“Transthyretin cardiac amyloidosis is a progressive disorder with a poor prognosis in the absence of treatment. The introduction of a new frontline therapeutic option that effectively stabilizes transthyretin and enhances patient outcomes provides additional avenues for those affected,” commented Martha Grogan from the Mayo Clinic.
“Promising data implies that Attruby may lessen all-cause mortality and cardiovascular hospitalizations as early as three months into treatment. Ongoing advancements in therapy are shifting this previously lethal condition into a manageable chronic cardiac ailment.”
Competitive Landscape
The area of transthyretin amyloidosis has garnered considerable attention among pharmaceutical developers over the past 20 years, giving rise to numerous new treatment options for various forms of the disease.
Several treatments have already received approval, such as Pfizer’s Vyndaqel (tafamidis), which was introduced in 2012. It is indicated for patients with ATTR-CM, as well as those with familial amyloid polyneuropathy and wild-type transthyretin amyloidosis.
Though the condition is relatively rare, tafamidis has seen impressive sales reaching nearly billion by the end of the third quarter this year. Acoramidis is anticipated to have comparable or superior effectiveness for ATTR-CM patients, with likely annual pricing being somewhat lower than tafamidis, making it compelling to observe how sales will measure up.
Another significant entity in this domain is Alnylam, which has created an RNA silencing treatment named Amvuttra (vutrisiran) for ATTR-CM, celebrating positive phase 3 results brought to light earlier this year. The company submitted the drug for FDA approval in October.