AstraZeneca’s Wainzua recommended for approval in the UK

AstraZeneca plc (LON:AZN) and Ionis’ Wainzua (eplontersen) has been recommended for approval by the Committee for Medicinal Products for Human Use (CHMP) in the European Union (EU) for the treatment of hereditary transthyretin-mediated amyloidosis in adult patients with stage 1 or stage 2 polyneuropathy, commonly referred to as hATTR-PN or ATTRv-PN.¹ If approved by the European Commission, Wainzua will be the only approved medicine in the EU for the treatment of ATTRv-PN that can be self-administered monthly via an auto-injector.^2-7

Recommendation based on NEURO-TTRansform Phase III results showing Wainzua demonstrated consistent and sustained benefit improving neuropathy impairment and quality of life versus placebo

The CHMP based its opinion on the positive NEURO-TTRansform Phase III trial which showed that through 66 weeks, patients treated with Wainzua demonstrated consistent and  sustained benefit on the co-primary endpoints of serum transthyretin (TTR) concentration and neuropathy impairment measured by modified Neuropathy Impairment Score +7 (mNIS+7), and key secondary endpoint of quality of life (QoL) on the Norfolk Quality of Life Questionnaire-Diabetic Neuropathy (Norfolk QoL-DN) versus external placebo.^2,8 Wainzua continued to demonstrate a favourable safety and tolerability profile throughout the NEURO-TTRansform trial.^2,8

ATTRv-PN is a debilitating disease that leads to peripheral nerve damage with motor disability within five years of diagnosis and, without treatment, is generally fatal within a decade.^9,10

Dr Laura Obici, Head of Rare Diseases Unit, Consultant at the Amyloidosis Research and Treatment Centre Istituto Di Ricovero e Cura a Carattere Scientifico Fondazione Policlinico San Matteo, Pavia, Italy, said: “This debilitating disease is ultimately fatal if left untreated and can have a significant impact on many aspects of patients’ and caregivers’ day-to-day lives. 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.”

Ruud Dobber, Executive Vice-President, BioPharmaceuticals Business Unit, AstraZeneca, said: “Due to the progressive nature of polyneuropathy of hereditary transthyretin-mediated amyloidosis, it is critical to have timely diagnosis and new therapies to help people have greater control over this potentially fatal disease. 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.”

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 transthyretin-mediated amyloidosis (ATTR).^2,3,11

Wainzua was approved under the brand name Wainua for the treatment of ATTRv-PN in the US in December 2023 and is now gaining approvals in additional countries worldwide.^11,12 As part of a global development and commercialisation agreement, AstraZeneca and Ionis are commercialising Wainua for the treatment of ATTRv-PN in the US.^11,12 The companies are seeking regulatory approval in the EU and other parts of the world, where AstraZeneca has exclusive rest of world commercialisation and development rights. Eplontersen was granted Orphan Drug Designation in the US and in the EU for the treatment of ATTR.^11,12

Eplontersen is currently being evaluated in the CARDIO-TTRansform Phase III trial for treatment of transthyretin-mediated amyloid cardiomyopathy (ATTR-CM), the largest of all ATTR-CM trials to date including over 1,400 participants.^11-14

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

References

1. European Medicines Agency [Internet]. Meeting highlights from the Committee for Medicinal Products for Human Use (CHMP) 14-17 October 2024 [cited 2024 October 18]. Available from: https://www.ema.europa.eu/en/news/meeting-highlights-committee-medicinal-products-human-use-chmp-14-17-october-2024.
2. Coelho T, et al. Eplontersen for hereditary transthyretin amyloidosis with polyneuropathy. JAMA. 2023;330(15):1448-1458.
3. Coelho T, et al. Characteristics of patients with hereditary transthyretin amyloidosis-polyneuropathy (ATTRv-PN) in NEURO-TTRansform, an open-label phase 3 study of eplontersen. Neurol Ther. 2023;12(1):267-287.
4. European Medicines Agency [Internet]. Vyndaqel (Tafamidis). Summary of product characteristics [cited 2024 October 8]. Available from: https://ec.europa.eu/health/documents/community-register/2020/20200217147074/anx_147074_en.pdf
5. European Medicines Agency [Internet]. Tegesdi (Inotersen). Summary of product characteristics [cited 2024 October 8]. Available from: https://www.ema.europa.eu/en/documents/product-information/tegsedi-epar-product-information_en.pdf.
6. European Medicines Agency [Internet]. Onpattro (Patisiran). Summary of product characteristics [cited 2024 October 8]. Available from: https://www.ema.europa.eu/en/documents/product-information/onpattro-epar-product-information_en.pdf.
7. European Medicines Agency [Internet]. Amvuttra (Vutrisiran). Summary of product characteristics [cited 2024 October 8]. Available from: https://www.ema.europa.eu/en/documents/product-information/amvuttra-epar-product-information_en.pdf.
8. AstraZeneca [Internet]. Press release. NEURO-TTRansform Phase III results presented at AAN showed eplontersen demonstrated consistent and sustained improvement in all measures of disease and quality of life through 66 weeks [cited 2024 October 8]. Available from: https://www.astrazeneca.com/media-centre/press-releases/2023/neuro-ttransform-phase-iii-results-presented-at-aan-showed-eplontersen-demonstrated-consistent-and-sustained-improvement.html.
9. Cortese A, et al. Diagnostic challenges in hereditary transthyretin amyloidosis with polyneuropathy: avoiding misdiagnosis of a treatable hereditary neuropathy. J Neurol Neurosurg Psychiatry. 2017;88(5):457-458. 
10. Nativi-Nicolau JN, et al. Screening for ATTR amyloidosis in the clinic: overlapping disorders, misdiagnosis, and multiorgan awareness. Heart Fail Rev. 2022;27(3):785-793.
11. Ionis Pharmaceuticals [Internet]. 2023 Annual Report [cited 2024 September 13]. Available from: https://ir.ionis.com/static-files/aad58173-0ab5-4142-b6d4-3e940c7eb2a6.
12. AstraZeneca [Internet]. Press release. Wainua (eplontersen) granted first-ever regulatory approval in the US for the treatment of adults with polyneuropathy of hereditary transthyretin-mediated amyloidosis [cited 2024 October 8]. Available from: https://www.astrazeneca.com/media-centre/press-releases/2023/wainua-eplontersen-granted-first-ever-regulatory-approval-us-treatment-of-adults-with-polyneuropathy-hereditary-transthyretin-mediated-amyloidosis.html.
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.