Acoramidis is indicated for the treatment of cardiomyopathy of wild-type or variant transthyretin-mediated amyloidosis (ATTR-CM) in adults to reduce cardiovascular death and cardiovascular-related hospitalization.
Tradename Attruby.
It is a near-complete (>90%) transthyretin stabilizer, developed to mimic the protective properties of the naturally-occurring T119M mutation, to treat transthyretin amyloid cardiomyopathy.
It is taken by mouth.
The most common adverse reactions include diarrhea and upper abdominal pain.
Acoramidis is indicated for the treatment of the cardiomyopathy of wild-type or variant transthyretin-mediated amyloidosis (ATTR-CM) in adults to reduce cardiovascular death and cardiovascular-related hospitalization.
ATTR-CM is a rare and serious disease that affects the heart muscle with is a build-up of protein deposits in the heart, causing the walls of the heart to become stiff, and making the left ventricle unable to properly relax and fill with blood.
This cardiomyopath progresses to the point the heart can become unable to pump blood out adequately, causing heart failure.
There are two types of ATTR-CM, hereditary ATTR-CM (hATTR-CM) and wild-type ATTR-CM (wATTR-CM).
In hATTR-CM, which can run in families, there’s a variant in the transthyretin gene, which results in protein deposits in the heart.
In wATTR-CM, there is no variant in the transthyretin gene.
Side effects The most common side effects are diarrhea and abdominal pain.[11]
Phase I data indicated acoramidis achieved near-complete (>90%) TTR stabilization across the entire dosing interval at steady state.
Phase II and the Open-Label Extension (OLE) data indicated after a median of 38 months, long-term treatment with acoramidis was generally well tolerated and resulted in a median decline in NT-proBNP levels, normalization of serum TTR, and sustained stabilization of TTR in individuals with ATTR-CM.
Phase III data from ATTRibute-CM indicated acoramidis resulted in a significantly better four-step primary hierarchical outcome containing components of mortality, morbidity, and function than placebo at 30 months in participants with ATTR-CM.
Other analyses indicated a 50% reduction in cumulative cardiovascular hospitalizations (CVH), a 42% reduction in all-cause mortality (ACM) and recurrent CVH.
A 3-month time-to-separation of the curves for ACM or CVH, demonstrated this degree of treatment effect this quickly in participants with ATTR-CM.
In vitro data indicated acoramidis exhibits near-complete (>90%) TTR stabilization at therapeutic trough concentrations, and its TTR stabilization exceeds that of tafamidis’ across a range of destabilizing TTR mutations.
Diarrhea (11.6% vs 7.6%) and upper abdominal pain (5.5% vs 1.4%) were reported in patients treated with Attruby versus placebo, respectively.
The majority of these adverse reactions were mild and resolved without drug discontinuation.
Discontinuation rates due to adverse events were similar between patients treated with acoramidis versus placebo (9.3% and 8.5%, respectively).