Eplontersen (Wainua) was approved by the FDA to treat polyneuropathy associated with hereditary transthyretin-mediated amyloidosis (ATTR) in adults, Ionis Pharmaceuticals and AstraZeneca announced on Thursday.
Hereditary ATTR is caused by a mutation in the TTR gene that results in the buildup of misfolded transthyretin protein, leading to amyloid deposits in the peripheral nerves (ATTR-PN) or heart (ATTR cardiomyopathy). ATTR-PN affects 30,000 to 40,000 people globally.
Eplontersen is a ligand-conjugated antisense oligonucleotide drug designed to reduce the production of TTR protein and treat both hereditary and non-hereditary forms of ATTR. Its efficacy was shown in the open-label, single-group, phase III NEURO-TTRansform trial.
In NEURO-TTRansform, the eplontersen group showed changes consistent with significantly lowered serum transthyretin concentration, less neuropathy impairment, and better quality of life compared with a historical placebo cohort. Adverse events by week 66 that led to study drug discontinuation occurred in 4% of the eplontersen group and 3% of the placebo group. Through week 66, there were two deaths in the eplontersen group — both consistent with known disease-related sequelae — and no deaths in the placebo group.
Eplontersen is the fourth approved drug for ATTR-PN and the second antisense oligonucleotide treatment. It will be available in the U.S. in January 2024 and is the only ATTR-PN drug that can be self-administered by an auto-injector, the drugmakers said.
“People with hereditary transthyretin-mediated amyloid polyneuropathy, and other forms of amyloidosis, are often misdiagnosed since symptoms can mirror other conditions,” Isabelle Lousada, president and CEO of the Amyloidosis Research Consortium, said in the drug companies’ press statement.
“The path to getting an accurate diagnosis can often be a long, arduous journey and it is critical that a timely and accurate diagnosis is made not only for the individual experiencing symptoms but for their families and loved ones,” she continued. “It is exciting to see new innovations coming through and increased efforts to raise awareness in an area that has often been overlooked or neglected.”
Eplontersen currently is being studied in the phase III CARDIO-TTRansform study for ATTR cardiomyopathy.