California-based BridgeBio has secured US FDA approval for its lead candidate drug, acoramidis (brand name Attruby) for treatment of transthyretin amyloid cardiomyopathy (ATTR-CM), an inherited heart condition.
This achievement is the end of a long road for the biotech and acoramidis, which previously failed to perform well against placebo in interim results from a phase 3 study in 2021 causing a massive share drop and big problems for the company.
But BridgeBio - citing better performance in the placebo group than expected, likely due to improved care for these patients overall - redesigned its phase 3 program and continued work to progress acoramidis despite the setbacks.
Now, the long awaited approval - announced on Friday - is based on the results of a phase 3 trial published earlier this year that showed a significant 42% reduction in a combined endpoint of all-cause mortality and cardiovascular events and a 50% reduction in cumulative cardiovascular events at 30 months compared with placebo.
In an open label extension study, the company showed that the drug continued to be effective over longer time periods with respective reductions in the two endpoints of 34% and 48% at 42 months.
The exact prevalence of ATTR-CM is uncertain but is thought to be higher than previously thought. Estimates have increased from 5 in 100,000 people in 2004 to 35 per 100,000 people in 2022. It is caused by production and aggregation of abnormal transthyretin protein in the heart. People with this condition experience a stiffening of the walls of the heart that impacts the way it beats, which often leads to diastolic dysfunction and later heart failure.
Acoramidis is an oral small molecule drug that stabilizes the transthyretin protein by mimicking a naturally extremely stable version of the protein (T119M variant) and reducing amyloid fibril build up and disease progression.
The trial showed acoramidis is able to almost completely stabilize transthyretin and preserve its function as a transporter of thyroxine and vitamin A, while also significantly reducing cardiovascular problems seen in these patients.
“Transthyretin cardiac amyloidosis is a progressive disease with a poor prognosis when left untreated. Having a new first line treatment option which provides excellent transthyretin stabilization and improves outcomes in this disease gives patients more options,” said Martha Grogan, of the Mayo Clinic, in a press statement.
“Encouraging data suggests Attruby 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.”
A competitive market
Transthyretin amyloidosis has attracted a lot of interest from drug developers over the last 20 years and a number of new treatments are in development for different forms of the condition.
Some of these treatments have already been approved, such as Pfizer’s Vyndaqel (tafamidis) in 2012. It is also indicated for people with ATTR-CM, as well as a form of the condition that impacts the nervous system known as familial amyloid polyneuropathy and wild-type transthyretin amyloidosis.
Despite the relative rareness of the condition, tafamidis has had very successful sales making almost $4 billion this year at the end of the third quarter. Acoramidis is estimated to have similar or better efficacy for patients with ATTR-CM and the estimated yearly pricing is likely to be somewhat lower than for tafamidis so it will be interesting to see how sales compare.
Another player in this space is Alnylam which has developed an RNA silencing therapy Amvuttra (vutrisiran) for people with ATTR-CM, which had very good phase 3 results published earlier this year. The company submitted the drug to the FDA for approval in October.