The National Institute for Health and Care Excellence (NICE) has issued final draft guidance recommending eplontersen (Wainzua) for the treatment of hereditary transthyretin-related amyloidosis (ATTR) in adults with stage 1 or 2 polyneuropathy in England and Wales. This announcement from AstraZeneca on October 29, 2024, closely follows the Committee for Medicinal Products for Human Use (CHMP) of the European Union's recommendation for approval and the FDA's approval in the United States in December 2023.
Clinical Impact and Expert Commentary
Tom Keith-Roach, president of AstraZeneca in the United Kingdom, emphasized the importance of this decision, stating that eligible patients now have access to a treatment that can be administered in-clinic or at home, supporting more personalized care. Paul Pozzo, chairman of Amyloidosis UK, noted that while there is no cure for ATTR amyloidosis, this approval offers an alternative treatment option for the UK ATTR community.
Marianna Fontana, a professor of cardiology and honorary consultant cardiologist at the National Amyloidosis Centre, University College London, highlighted that eplontersen provides a new, disease-modifying treatment option for eligible patients with ATTR-PN. She noted that without treatment, ATTR-PN can lead to extreme polyneuropathy, severe disability, and premature death. The Phase III NEURO-TTRansform trial demonstrated that eplontersen significantly lowered serum transthyretin concentration, resulting in less neuropathic impairment and an improved quality of life for patients.
Scientific Basis and Trial Data
The NICE recommendation is based on the 66-week Phase III NEURO-TTRansform trial. ATTR-PN is caused by a mutation in the transthyretin (TTR) gene, which leads to misfolding of the TTR protein and accumulation of amyloid fibrils, damaging peripheral nerves. AstraZeneca notes that ATTR-PN is frequently under-recognized due to its heterogeneous and non-specific clinical manifestations. Untreated, the severe polyneuropathy and motor disability that develops within five years of onset can result in death within a decade.
