The Committee for Medicinal Products for Human Use (CHMP) has recommended AstraZeneca and Ionis' Wainzua (eplontersen) for approval in the European Union (EU) for the treatment of hereditary transthyretin-mediated amyloidosis (hATTR), specifically in adult patients with stage 1 or stage 2 polyneuropathy (ATTRv-PN). This decision, announced on October 21, 2024, brings Wainzua one step closer to becoming the only approved medicine in the EU for ATTRv-PN that can be self-administered monthly via an auto-injector.
The recommendation is based on positive results from the NEURO-TTRansform Phase III trial, a global, open-label, randomized study. The trial demonstrated that through 66 weeks, patients treated with Wainzua experienced consistent and sustained benefits in neuropathy impairment and quality of life compared to placebo. Specifically, the co-primary endpoints of serum transthyretin (TTR) concentration and neuropathy impairment, measured by modified Neuropathy Impairment Score +7 (mNIS+7), along with the key secondary endpoint of quality of life (QoL) on the Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QoL-DN), showed significant improvement versus the external placebo.
Clinical Significance
ATTRv-PN is a debilitating and progressive disease characterized by the accumulation of misfolded TTR protein in tissues, leading to peripheral nerve damage and motor disability. Without treatment, the condition is generally fatal within a decade of diagnosis. The current treatment landscape includes therapies aimed at reducing TTR production or stabilizing the TTR protein, but an easily self-administered option has been lacking.
Dr. Laura Obici, Head of Rare Diseases Unit at the Amyloidosis Research and Treatment Centre, emphasized the importance of new treatment options: "Having additional amyloidosis treatment options designed to reduce the production of TTR protein at its source would potentially give patients more time and ability to do what matters most to them and offer the hope of living longer with a higher quality of life."
Wainzua's Mechanism of Action
Wainzua (eplontersen) is a once-monthly RNA-targeted medicine designed to reduce the production of TTR protein at its source in the liver. This mechanism of action aims to address all types of transthyretin-mediated amyloidosis (ATTR).
Ruud Dobber, Executive Vice-President, BioPharmaceuticals Business Unit, AstraZeneca, highlighted the critical need for timely diagnosis and new therapies: "Today’s recommendation brings Wainzua one step closer for patients in Europe, and if approved, will offer a new treatment option that can provide consistent TTR suppression and results in improved quality of life."
Ongoing Research
Eplontersen is also being evaluated in the CARDIO-TTRansform Phase III trial for the treatment of transthyretin-mediated amyloid cardiomyopathy (ATTR-CM). This trial, which has fully enrolled over 1,400 participants, is the largest ATTR-CM trial to date.
