Eplontersen granted Orphan Drug Designation in the US for transthyretin amyloidosis

Eplontersen has been granted Orphan Drug Designation (ODD) in the US by the Food and Drug Administration (FDA) for the treatment of transthyretin-mediated amyloidosis, a systemic, progressive and fatal condition.

Eplontersen, formerly known as IONIS-TTR-L_Rx, is a ligand-conjugated antisense (LICA) 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).

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.^2,3 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

The FDA grants ODD status to medicines and potential new medicines intended for the treatment, diagnosis or prevention of rare diseases or disorders that affect fewer than 200,000 people in the US.

Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, AstraZeneca, said: “Eplontersen has the potential to be a best-in-class treatment to halt the progression of transthyretin-mediated amyloidosis and treat this fatal condition. The FDA designation further underscores the potential for eplontersen to offer new hope to this patient population currently faced with limited treatment options.”

As part of a global development and commercialization agreement with Ionis Pharmaceuticals, Inc. (Ionis) eplontersen will be jointly developed and commercialized by both companies in the US, and will be developed and commercialized in the rest of the world, except in Latin America, by AstraZeneca.

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.

Notes

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.² 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

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.

AstraZeneca in CVRM

Cardiovascular, Renal and Metabolism (CVRM), part of BioPharmaceuticals, forms one of AstraZeneca’s three 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 and pancreas, AstraZeneca is investing in a portfolio of medicines for organ protection and improving outcomes by slowing disease progression, reducing risks and tackling co-morbidities. The Company’s ambition is to modify or halt the natural course of CVRM diseases and potentially regenerate organs and restore function, by continuing to deliver transformative science that improves treatment practices and CV health for millions of patients worldwide.

About AstraZeneca

AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization 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. For more information, please visit www.astrazeneca-us.com and follow us on Twitter @AstraZenecaUS.

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

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