Wainzua Receives EU Recommendation for Treating Hereditary Amyloidosis, Offering New Monthly Self-Administered Option

Wainzua Receives EU Recommendation for Treating Hereditary Amyloidosis, Offering New Monthly Self-Administered Option

(IN BRIEF) AstraZeneca and Ionis’ drug Wainzua (eplontersen) has been recommended for approval in the European Union for treating hereditary transthyretin-mediated amyloidosis (ATTRv-PN) in adults with stage 1 or 2 polyneuropathy. Based on the positive results from the NEURO-TTRansform Phase III trial, which showed significant improvements in neuropathy impairment and quality of life compared to placebo, Wainzua offers a new treatment option that can be self-administered monthly via an auto-injector. The drug was previously approved in the US in December 2023 and is now seeking further global regulatory approvals.

(PRESS RELEASE) CAMBRIDGE, 21-Oct-2024 — /EuropaWire/ — On October 21, 2024, AstraZeneca and Ionis Pharmaceuticals announced that their drug, Wainzua (eplontersen), has been recommended for approval by the Committee for Medicinal Products for Human Use (CHMP) in the European Union (EU). The drug is intended for the treatment of hereditary transthyretin-mediated amyloidosis (ATTRv-PN) in adults with stage 1 or stage 2 polyneuropathy. If approved by the European Commission, Wainzua will be the first medicine in the EU for ATTRv-PN that can be self-administered monthly via an auto-injector.

The CHMP’s positive recommendation is based on findings from the NEURO-TTRansform Phase III trial. This trial demonstrated significant and sustained benefits over 66 weeks, with improvements in serum transthyretin (TTR) concentration, neuropathy impairment (measured by modified Neuropathy Impairment Score +7), and quality of life (measured by the Norfolk QoL-Diabetic Neuropathy questionnaire) when compared to placebo. Wainzua was also found to have a favorable safety and tolerability profile.

ATTRv-PN is a debilitating disease that leads to severe nerve damage and motor disability, often proving fatal within a decade without treatment. Wainzua targets TTR production in the liver, providing a once-monthly treatment option designed to suppress TTR levels and potentially offer better quality of life and longevity for patients.

Dr. Laura Obici, an amyloidosis expert from Italy, emphasized that this disease drastically affects patients’ quality of life, and treatments that suppress TTR at the source could give patients more time and improve their ability to manage daily activities. Ruud Dobber, Executive Vice-President of AstraZeneca’s BioPharmaceuticals Unit, expressed optimism about Wainzua’s potential to offer patients in Europe a new treatment option for this life-threatening condition.

Wainzua was approved for ATTRv-PN treatment in the United States in December 2023 and is now gaining regulatory approvals globally. The drug is also being evaluated in a Phase III trial for transthyretin-mediated amyloid cardiomyopathy (ATTR-CM).

Notes

TTR Amyloidosis
ATTR is caused by the accumulation of liver-derived misfolded TTR protein in tissues, such as the heart and the peripheral nerves, causing organ damage and failure.2,15 ATTR then causes complications, leading to cardiovascular, neurological and renal diseases such as heart failure (HF) and chronic kidney disease.15,16 There are both hereditary (ATTRv) and non-hereditary (wild-type) forms of ATTR.15 ATTR is a rapidly progressive and fatal disease that requires timely recognition of symptoms.15,17 ATTR has several phenotypes including ATTR-CM, which predominantly impacts the heart, potentially leading to HF, ATTRv-PN, which predominantly affects the peripheral nervous system, and mixed phenotype, where patients experience symptoms of both.15,18 Worldwide, there are an estimated 300,000 – 500,000 patients with ATTR-CM and about 10,000 – 40,000 patients with ATTRv-PN.11,18

NEURO-TTRansform
NEURO-TTRansform is a global, open-label, randomised trial evaluating the efficacy and safety of eplontersen in patients with ATTRv-PN.2,19 The trial enrolled adult patients with ATTRv-PN Stage 1 or Stage 2 compared to the external placebo.2,19 The comparison of efficacy and safety for eplontersen versus external placebo was based on data up to week 66.2,19 All patients were then followed on treatment until week 85 and evaluated four weeks after the last dose in an end-of-trial assessment.2,19 Following treatment and the end-of-trial assessments, patients were eligible to enter an open-label extension study, which is still ongoing.2 Full results from the NEURO-TTRansform trial were published in The Journal of the American Medical Association (JAMA) further demonstrating the benefit of Wainzua across the spectrum of ATTRv-PN at 35, 66 and 85 weeks of treatment.2,19

Wainzua
Wainzua is a once-monthly silencer that provides upstream suppression of TTR production.2,3,11 It is an RNA-targeted medicine designed to reduce production of TTR protein at its source in the liver to potentially treat all types of ATTR.2,3,11

AstraZeneca in CVRM
Cardiovascular, Renal and Metabolism (CVRM), part of BioPharmaceuticals, forms one of AstraZeneca’s main disease areas and is a key growth driver for the Company. By following the science to understand more clearly the underlying links between the heart, kidneys, liver and pancreas, AstraZeneca is investing in a portfolio of medicines for organ protection by slowing or stopping disease progression, and ultimately paving the way towards regenerative therapies. The Company’s ambition is to improve and save the lives of millions of people, by better understanding the interconnections between CVRM diseases and targeting the mechanisms that drive them, so we can detect, diagnose and treat people earlier and more effectively.

AstraZeneca
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References

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13. ClinicalTrials.gov [Internet]. CARDIO-TTRansform: a study to evaluate the efficacy and safety of eplontersen (formerly known as ION-682884, IONIS-TTR-LRx and AKCEA-TTR-LRx) in participants with transthyretin-mediated amyloid cardiomyopathy (ATTR CM) [cited 2024 October 8]. Available from https://www.clinicaltrials.gov/study/NCT04136171.
14. Ionis [Internet]. Ionis completes enrollment in landmark Phase 3 CARDIO-TTRansform study in patients with TTR-mediated amyloid cardiomyopathy. 2023 July 31 [cited 2024 October 8]. Available from https://ir.ionis.com/news-releases/news-release-details/ionis-completes-enrollment-landmark-phase-3-cardio-ttransform#:~:text=CARDIO%2DTTRansform%20is%20the%20largest,threatening%20cardiovascular%20(CV)%20events.
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19. Coelho T, et al. Design and rationale of the global phase 3 NEURO-TTRansform study of antisense oligonucleotide AKCEA-TTR-LRx(ION-682884-CS3) in hereditary transthyretin-mediated amyloid polyneuropathy. Neurol Ther. 2021;10(1):375-389.

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AstraZeneca PLC

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