CHMP Recommends WAINZUA (eplontersen) for EU Approval to Treat Hereditary Transthyretin-Mediated Polyneuropathy in Adults

Ionis Pharmaceuticals, Inc. and AstraZeneca have announced a significant milestone with their drug WAINZUA (eplontersen) receiving a positive recommendation for approval from the Committee for Medicinal Products for Human Use (CHMP) in the European Union. This recommendation pertains to the treatment of hereditary transthyretin-mediated amyloidosis in adult patients with stage 1 or stage 2 polyneuropathy, commonly known as ATTRv-PN. Upon approval by the European Commission, WAINZUA will become the sole approved medication in the EU for ATTRv-PN that can be self-administered monthly via an auto-injector.

The favorable CHMP opinion is based on the NEURO-TTRansform Phase 3 clinical trial results. The trial demonstrated that WAINZUA provided consistent and sustained benefits over 66 weeks on primary endpoints such as serum transthyretin (TTR) concentration and neuropathy impairment, measured by the modified Neuropathy Impairment Score +7 (mNIS+7). It also showed significant improvements in quality of life, assessed by the Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QoL-DN), compared to a placebo. Throughout the trial, WAINZUA maintained a positive safety and tolerability profile.

ATTRv-PN is a severe disease that progressively damages peripheral nerves, leading to motor disabilities within five years and proving fatal within ten years if untreated. WAINZUA, an RNA-targeted medication, works by reducing TTR protein production at its source.

Brett P. Monia, CEO of Ionis, emphasized the importance of this development, noting that hereditary transthyretin-mediated amyloidosis with polyneuropathy continues to be a progressive and debilitating condition in Europe and globally. He pointed out that the CHMP recommendation marks a crucial step in making WAINZUA available in Europe. If approved, WAINZUA will be unique in its self-administration feature, providing significant convenience for patients. Monia expressed pride in the partnership with AstraZeneca, highlighting their global expertise and leadership in efficiently bringing this treatment to many affected individuals in Europe, pending regulatory approval.

In December 2023, the U.S. granted approval for eplontersen under the brand name WAINUA™ for treating ATTRv-PN. The drug is also gaining approval in other countries, including Canada. Under a global development and commercialization agreement, Ionis and AstraZeneca are marketing WAINUA in the U.S. and seeking regulatory approval in other regions where AstraZeneca holds exclusive rights.

Additionally, eplontersen is being evaluated in the global CARDIO-TTRansform Phase 3 study for treating ATTR-CM in adults. This extensive trial, fully enrolled with over 1,400 participants, aims to be the most comprehensive study for this patient group.

Hereditary ATTR amyloidosis is caused by the accumulation of misfolded TTR protein produced by the liver, leading to organ damage and failure. It manifests in various forms, including ATTR-cardiomyopathy (affecting the heart), ATTR-polyneuropathy (affecting the peripheral nervous system), and mixed phenotype. Worldwide, there are estimated to be between 300,000 to 500,000 patients with ATTR-CM and approximately 10,000 to 40,000 patients with ATTRv-PN.

The NEURO-TTRansform trial is a global, open-label, randomized study evaluating eplontersen's efficacy and safety. The final analysis, completed at week 66, compared eplontersen to an external placebo group. Patients continued on treatment until week 85 and were evaluated four weeks after the final dose. Post-trial, patients had the option to enter an open-label extension study for continued treatment or a 20-week post-treatment evaluation period.

Eplontersen is a once-monthly, RNA-targeted medication designed to reduce TTR protein production at its liver source. It is already approved in the U.S. and Canada under the brand name WAINUA™ for treating hereditary transthyretin-mediated amyloidosis in adults. WAINZUA is pending approval in Europe for any indication.