EU Approves WAINZUA for Treating Hereditary Transthyretin Amyloidosis Polyneuropathy

CARLSBAD, Calif.—Ionis Pharmaceuticals, Inc. and AstraZeneca have announced the successful approval of WAINZUA (eplontersen) in the European Union for treating hereditary transthyretin-mediated amyloidosis, specifically in adults with stage 1 or stage 2 polyneuropathy, known as hATTR-PN or ATTRv-PN. This marks the second major approval for WAINZUA, which is already marketed in the U.S. under the name WAINUA™. This breakthrough provides the only EU-sanctioned treatment for ATTRv-PN that patients can self-administer monthly using an auto-injector.

The European Commission's approval follows a favorable recommendation from the Committee for Medicinal Products for Human Use (CHMP). The decision was largely based on the promising results of the NEURO-TTRansform Phase 3 study. This trial demonstrated that WAINZUA provided consistent and enduring benefits over 66 weeks, significantly improving neuropathy impairment and patient's quality of life compared to placebo. The key indicators of success included serum transthyretin (TTR) concentration and neuropathy impairment, along with quality of life assessed via the Norfolk Quality of Life Questionnaire-Diabetic Neuropathy.

ATTRv-PN is a severe condition leading to peripheral nerve damage, causing motor disability within five years from diagnosis, and often proving fatal within ten years without intervention. WAINZUA, an RNA-targeted treatment, is designed to curtail the production of TTR protein at its source, offering a once-monthly dosing schedule.

“This approval is a significant milestone, providing a new option that patients can administer themselves, ensuring consistent suppression of transthyretin production, and improving their quality of life,” stated Brett P. Monia, Ph.D., CEO of Ionis Pharmaceuticals. The recent EU approval complements existing approvals in North America, the UK, and other countries, showcasing the rapid progress in global delivery of WAINZUA.

The regulatory journey of WAINZUA began with its approval in the United States under the brand name WAINUA in December 2023. It has since gained approval in Canada and the United Kingdom. Ionis and AstraZeneca are working under a global development and commercialization agreement, with AstraZeneca holding exclusive rights for commercialization and development outside the U.S.

The condition transthyretin amyloidosis (ATTR) arises when misfolded TTR proteins, derived from the liver, accumulate in tissues, damaging organs such as the heart and peripheral nerves. This accumulation leads to complications, including cardiovascular, neurological, and renal diseases. ATTR manifests in hereditary (ATTRv) and non-hereditary forms, and can affect the heart leading to heart failure (ATTR-CM), or the nervous system, causing polyneuropathy (ATTR-PN). The disease is notably progressive and fatal, requiring prompt symptom recognition.

During the NEURO-TTRansform study, participants were assessed at 35, 66, and 85 weeks. The final comparative analysis took place at 66 weeks against an external placebo group, continuing treatment until week 85 before an end-of-trial evaluation. Participants could then opt for an open-label extension study to continue receiving eplontersen or enter a post-treatment evaluation period.

Eplontersen is an RNA-targeted medicine that significantly reduces the production of TTR protein from the liver, offering upstream suppression. It is also being studied in the CARDIO-TTRansform Phase 3 trial for treating ATTR-CM, with over 1,400 patients enrolled, making it the most extensive study of its kind.