- Source: Acoramidis
Acoramidis /ə-corAM’-i-dis/ (formerly AG10, named for "Alhamadsheh-Graef molecule 10") is an investigational, near-complete (>90%) transthyretin stabilizer, developed to mimic the protective properties of the naturally-occurring T119M mutation, to treat transthyretin amyloid cardiomyopathy. It is delivered by mouth. An alternative treatment is tafamidis. Acoramidis is pending FDA approval (PDUFA Nov. 29, 2024) for the treatment of both wild-type and hereditary transthyretin amyloid cardiomyopathy (ATTR-CM) to reduce cardiovascular death and hospitalization.
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.
Phase 1 data indicated acoramidis achieved near-complete (>90%) TTR stabilization across the entire dosing interval at steady state.
Phase 2 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 3 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 patients with ATTR-CM. Adverse events were similar in the two groups.
Other analyses from ATTRibute-CM indicated a 50% reduction in cumulative cardiovascular hospitalizations (CVH), a 42% reduction in all-cause mortality (ACM) and recurrent CVH, and a 3-month time-to-separation of the Kaplan Meier curves for ACM or CVH. No other treatment has demonstrated this degree of treatment effect this quickly in patients with ATTR-CM.
