The European Commission (EC) has approved WAINZUA (eplontersen) for the treatment of hereditary transthyretin-mediated amyloidosis in adult patients with stage 1 or stage 2 polyneuropathy (ATTRv-PN), Ionis Pharmaceuticals and AstraZeneca announced today. This approval makes WAINZUA the only medicine for ATTRv-PN in the European Union that can be self-administered monthly via an auto-injector.
The EC approval follows a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) and is based on compelling data from the NEURO-TTRansform Phase 3 clinical trial.
Disease Impact and Treatment Need
ATTRv-PN is a debilitating, progressive disease caused by the accumulation of misfolded transthyretin (TTR) protein in peripheral nerves. Without treatment, the condition leads to severe nerve damage and motor disability within five years of diagnosis and is generally fatal within a decade. Worldwide, an estimated 10,000 to 40,000 patients suffer from ATTRv-PN.
"Today's approval of WAINZUA in Europe offers adults with hereditary transthyretin-mediated amyloidosis with polyneuropathy a new, self-administered treatment option that provides consistent suppression of transthyretin production and improves neuropathy impairment and quality of life," said Brett P. Monia, Ph.D., chief executive officer of Ionis Pharmaceuticals.
Clinical Evidence Supporting Approval
The NEURO-TTRansform trial was a global, open-label, randomized study evaluating eplontersen's efficacy and safety in ATTRv-PN patients. Through 66 weeks, patients receiving WAINZUA demonstrated consistent and sustained benefits on two co-primary endpoints:
- Reduction in serum transthyretin (TTR) concentration
- Improvement in neuropathy impairment as measured by the modified Neuropathy Impairment Score +7 (mNIS+7)
Additionally, the trial showed significant improvement in the key secondary endpoint of quality of life, measured by the Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QoL-DN), compared to an external placebo group.
WAINZUA maintained a favorable safety and tolerability profile throughout the trial. The most common adverse reactions (≥9% in treated patients) were decreased vitamin A levels (15%) and vomiting (9%).
Full results from the NEURO-TTRansform trial were published in The Journal of the American Medical Association (JAMA), demonstrating eplontersen's benefit across the spectrum of ATTRv-PN at 35, 66, and 85 weeks of treatment.
Mechanism of Action
WAINZUA is a once-monthly RNA-targeted medicine designed to reduce TTR protein production at its source in the liver. This upstream suppression approach helps prevent the accumulation of misfolded TTR protein in tissues, which is the underlying cause of organ damage in ATTR.
Global Regulatory Status
WAINZUA has already received approval under the brand name WAINUA for the treatment of ATTRv-PN in the United States (December 2023), Canada, and the United Kingdom. As part of their global development and commercialization agreement, AstraZeneca and Ionis are jointly developing and commercializing the treatment in the U.S., while seeking regulatory approvals in other regions where AstraZeneca holds exclusive commercialization and development rights.
Ongoing Research
Beyond ATTRv-PN, eplontersen is currently being evaluated in the global CARDIO-TTRansform Phase 3 study for the treatment of adults with ATTR cardiomyopathy (ATTR-CM), a form of the disease that predominantly affects the heart. This trial has enrolled more than 1,400 patients, making it the largest and most comprehensive study to date in this patient population.
About Transthyretin Amyloidosis
Transthyretin amyloidosis (ATTR) occurs when misfolded TTR protein accumulates in various tissues, causing organ damage and failure. The condition can manifest as cardiomyopathy (affecting the heart), polyneuropathy (affecting the peripheral nervous system), or as a mixed phenotype with symptoms of both.
ATTR exists in both hereditary (ATTRv) and non-hereditary (wild-type) forms. Globally, there are an estimated 300,000 to 500,000 patients with ATTR-CM and approximately 10,000 to 40,000 patients with ATTRv-PN.
The approval of WAINZUA represents a significant advancement in the treatment landscape for ATTRv-PN, offering patients a convenient self-administered option that addresses the underlying disease mechanism and has demonstrated meaningful clinical benefits.
