The U.S. Food and Drug Administration (FDA) has granted approval for Eplontersen (Wainua) as a treatment option for polyneuropathy associated with hereditary transthyretin-mediated amyloidosis (ATTR). This significant development was jointly announced by Ionis Pharmaceuticals and AstraZeneca. ATTR-PN, which affects a global population of around 30,000 to 40,000 individuals, occurs due to a mutation in the TTR gene. This mutation leads to the accumulation of misfolded transthyretin protein, causing amyloid deposits in the peripheral nerves or heart.
Eplontersen is categorized as a ligand-conjugated antisense oligonucleotide drug. Its primary purpose is to reduce the production of TTR protein, thus addressing both hereditary and non-hereditary forms of ATTR. The effectiveness of Eplontersen was demonstrated in the phase III NEURO-TTRansform trial, which was an open-label, single-group study. The group receiving Eplontersen exhibited significant improvement, with lowered serum transthyretin concentration, reduced neuropathy impairment, and a better overall quality of life compared to a placebo cohort.
Safety and Tolerability
Adverse events leading to the discontinuation of the study drug occurred in 4% of the Eplontersen group and 3% of the placebo group by week 66. Two deaths were reported in the Eplontersen group, both consistent with known disease-related complications, while there were no deaths in the placebo group. These findings suggest that Eplontersen is generally well-tolerated and has an acceptable safety profile.
Eplontersen is the fourth drug to receive FDA approval for the treatment of ATTR-PN. It is also the second antisense oligonucleotide treatment to be approved. Notably, Eplontersen is the only drug for ATTR-PN that can be self-administered using an auto-injector. This feature provides patients with greater convenience and autonomy in managing their condition. The drug is set to be available in the United States starting from January 2024.
Patients with hereditary transthyretin-mediated amyloid polyneuropathy, as well as other forms of amyloidosis, often face challenges in obtaining an accurate diagnosis. The symptoms of these conditions can mimic other diseases, leading to misdiagnosis and delays in appropriate treatment. Isabelle Lousada, President and CEO of the Amyloidosis Research Consortium, highlights the critical need for timely and accurate diagnoses for affected individuals, their families, and loved ones. The approval of Eplontersen represents an encouraging advancement in raising awareness and addressing the diagnostic challenges associated with amyloidosis.
Eplontersen is currently under investigation in the phase III CARDIO-TTRansform study for ATTR cardiomyopathy. The outcome of this study will provide valuable insights into the drug’s efficacy and safety in treating this specific manifestation of ATTR. Continued research and development efforts in the field of amyloidosis hold promise for further advancements in diagnosis and treatment options.
The approval of Eplontersen by the FDA for the treatment of polyneuropathy associated with hereditary transthyretin-mediated amyloidosis represents a significant milestone. The drug’s mechanism of action, efficacy, and tolerability make it a promising option for individuals living with this condition. The availability of Eplontersen in a self-administered form further enhances patient independence and convenience. Looking ahead, ongoing research and awareness initiatives will contribute to further progress in the diagnosis and management of amyloidosis.