Márcia Waddington-Cruz, MD, PhD, Federal University of Rio de Janeiro, discusses a Phase 3 trial testing eplontersen in adult patients with hereditary transthyretin amyloidosis.


Hereditary transthyretin amyloidosis (hATTR) is a rare genetic condition characterized by abnormal build-up of a protein called amyloid in the body’s organs and tissues. hATTR is caused by changes in the TTR gene. Signs and symptoms depend on where the amyloid protein is building up. Amyloid build-up in the nerves of the peripheral nervous system causes a loss of sensation in the lower limbs, feet, and hands. Amyloid build-up can also affect the involuntary body functions, such as blood pressure, heart rate, and digestion. Other areas of the body that may be affected are the heart, kidneys, eyes, and gastrointestinal tract.

Current management of hATTR focuses on prolonging disease progression and managing patient symptoms.

NEURO-TTRansform was an open-label, single-group, Phase 3 trial evaluating eplontersen, an investigational ligand-conjugated antisense oligonucleotide, in adults with ATTRv polyneuropathy.

At week 65, adjusted mean percentage reduction in serum transthyretin was -81.7% with eplontersen as compared to -11.2% with placebo. Adjusted mean change from baseline to week 66 was better with eplontersen vs placebo for mNIS+7 composite score (0.3 vs 25.1; difference, -24.8 [95% CI, -31.0 to -18.6; P < .001) and for Norfolk QoL-DN (-5.5 vs 14.2; difference, -19.7 [95% CI, -25.6 to -13.8]; P < .001). Adverse events by week 66 that led to study drug discontinuation occurred in 6 patients (4%) in the eplontersen group vs 2 (3%) in the placebo group. Through week 66, there were 2 deaths in the eplontersen group consistent with known disease-related sequelae (cardiac arrhythmia; intracerebral hemorrhage); there were no deaths in the placebo group.

In patients with ATTRv polyneuropathy, the eplontersen treatment group demonstrated changes consistent with significantly lowered serum transthyretin concentration, less neuropathy impairment, and better quality of life compared with a placebo.

To learn more about rare genetic conditions, visit https://checkrare.com/diseases/congenital-and-genetic-conditions/