AstraZeneca and Ionis sign deal to develop and commercialise eplontersen

7 December 2021 07:00 GMT Liver-targeted antisense therapy in Phase III development for the treatment of transthyretin amyloidosis, a systemic, progressive and fatal condition AstraZeneca has entered into a new global development and commercialisation agreement with Ionis Pharmaceuticals, Inc. (Ionis) for eplontersen, formerly known as IONIS-TTR-L RX. Eplontersen is a ligand-conjugated antisense investigational medicine currently in Phase III clinical trials for amyloid transthyretin cardiomyopathy (ATTR-CM) and amyloid transthyretin polyneuropathy (ATTR-PN). It is designed to reduce the production of transthyretin (TTR protein) to treat both hereditary and non-hereditary forms of TTR amyloidosis (ATTR). The companies will jointly develop and commercialise eplontersen in the US, while AstraZeneca will develop and commercialise it in the rest of the world, except in Latin America. ATTR-CM is a systemic, progressive and fatal condition that leads to progressive heart failure and death within four years from diagnosis. 1 It remains underdiagnosed and its prevalence is thought to be underestimated due to a lack of disease awareness and the heterogeneity of symptoms. 2 Hereditary ATTR-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. 3 Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, AstraZeneca, said: “Eplontersen has the potential to halt the progression of TTR-mediated amyloidosis, irrespective of whether it’s caused by genetic mutations or aging. Thanks to its precise liver-targeting properties, it also has the potential to be a best-in-class treatment for patients suffering from this devastating disease and who currently have limited options.” Hereditary ATTR-PN is expected to be the first indication for which the companies will seek regulatory approval for eplontersen, with the potential to file a new drug application with the US Food and Drug Administration by the end of 2022. Financial considerations AstraZeneca will pay Ionis an upfront payment of $200m and additional conditional payments of up to $485m following regulatory approvals. It will also pay up to $2.9bn of sales-related milestones based on sales thresholds between $500m and $6bn, plus royalties in the range of low double-digit to mid-twenties percentage depending on the region. The collaboration includes territory-specific development, commercial and medical affairs cost-sharing provisions. The transaction will be funded with cash and is expected to be neutral to Core earnings in 2021. It will be accounted for as an intangible asset acquisition, recognised initially at the upfront amount, with any potential future milestone payments capitalised into the intangible asset as they are recognised. Ionis will continue to manufacture and supply eplontersen for the existing clinical studies and process qualification. AstraZeneca will be responsible for commercial supply, with transition timing to be agreed by both parties. AstraZeneca will book all sales generated under the agreement. The transaction is expected to close in the fourth quarter of 2021, subject to customary closing conditions and regulatory clearances. The transaction does not impact the AstraZeneca’s financial guidance for 2021. Notes Eplontersen Eplontersen is a ligand-conjugated antisense (LICA) investigational medicine designed to reduce the production of transthyretin, or TTR protein, to treat all types of ATTR, a systemic, progressive and fatal disease. TTR Amyloidosis (ATTR) Cardiomyopathy and polyneuropathy due to ATTR are caused by aging or genetic mutations resulting in misfolded TTR protein and accumulation as amyloid fibrils in the cardiac myocardium and peripheral nerves, respectively. In patients with ATTR, both the mutant and wild type TTR protein builds up as fibrils in tissues, such as the peripheral nerves, heart, gastrointestinal system, eyes, kidneys, central nervous system, thyroid and bone marrow. The presence of TTR fibrils interferes with the normal functions of these tissues. As the TTR protein fibrils enlarge, more tissue damage occurs and the disease worsens, resulting in poor quality of life and eventually death. Worldwide, there are an estimated 300,000 - 500,000 patients with ATTR-CM 4,5 and 10,000 - 40,000 patients with ATTR-PN 2 . AstraZeneca AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on Twitter @AstraZeneca . Contacts For details on how to contact the Investor Relations Team, please click here . For Media contacts, click here . References 1. Lauppe RE, et al . Nationwide prevalence and characteristics of transthyretin amyloid cardiomyopathy in Sweden. Open Heart . 2021 Oct;8(2):e001755. doi: 10.1136/openhrt-2021-001755. 2. González-Duarte A, et al . Impact of non-cardiac clinicopathologic characteristics on survival in transthyretin amyloid polyneuropathy. Neurol Ther . 2020;9(1):135-149. doi:10.1007/s40120-020-00183-7. 3. Cortese A, et al . Diagnostic challenges in hereditary transthyretin amyloidosis with polyneuropathy: avoiding misdiagnosis of a treatable hereditary neuropathy. J Neurol Neurosurg Psychiatry . 2017 May;88(5):457-458. doi: 10.1136/jnnp-2016-315262. 4. Mohamed-Salem L, et al . Prevalence of wild type ATTR assessed as myocardial uptake in bone scan in the elderly population. Int J Cardiol . 2018 Nov 1;270:192-196. doi: 10.1016/j.ijcard.2018.06.006. 5. Cuscaden C, et al . Estimation of prevalence of transthyretin (ATTR) cardiac amyloidosis in an Australian subpopulation using bone scans with echocardiography and clinical correlation. J Nucl Cardiol. 2020 May 8. doi: 10.1007/s12350-020-02152-x. Adrian Kemp Company Secretary AstraZeneca PLC tags Partnering Corporate and financial AstraZeneca Websites This website is intended for people seeking information on AstraZeneca's worldwide business. Our country sites can be located in the AZ Network. Veeva ID: Z4-25396 Date of next review: August 2022 Resources All resources Open Innovation Externally sponsored scientific research Medical Information for HCPs US prescription assistance programmes Global clinical trials information Medicines Report a possible side effect Quick links Media Investor Relations Partnering Careers Sustainability Modern Slavery Statement AZethics – Report A Concern Supplier information Social Media Community Guidelines Social Media YouTube Instagram Glassdoor Facebook utility links Legal notice and Terms of Use Privacy notice Site map Contact us Cookie policy © AstraZeneca 2022 You are now leaving AstraZeneca.com You have selected a link that will take you to a site maintained by a third party who is solely responsible for its contents. AstraZeneca provides this link as a service to website visitors. AstraZeneca is not responsible for the privacy policy of any third party websites. We encourage you to read the privacy policy of every website you visit. Click ‘cancel’ to return to AstraZeneca’s site or ‘continue’ to proceed. Cancel Continue ? Important notice for users You are about to access AstraZeneca historic archive material. Any reference in these archives to AstraZeneca products or their uses may not reflect current medical knowledge and should not be used as a source of information on the present product label, efficacy data or safety data. Please refer to your approved national product label (SmPC) for current product information. I have read this warning and will not be using any of the contained product information for clinical purposes. I disagree I agree ? ?

The release as fetched from its publisher. astrazeneca.com ↗