[Translation] A Phase III, randomized, double-blind, placebo-controlled, multicenter study evaluating the efficacy and safety of the amyloid depleting agent ALXN2220 in adult subjects with transthyretin amyloid cardiomyopathy (ATTR-CM)

评价ALXN2220在接受标准治疗的ATTR-CM成人受试者中的有效性和安全性。

[Translation]

To evaluate the efficacy and safety of ALXN2220 in adult subjects with ATTR-CM who are receiving standard of care.

Start Date27 Jun 2024

Sponsor / Collaborator

AstraZeneca Global R&D (China) Co., Ltd.

CTIS2023-506669-70-00 / Recruiting

A Phase 3, Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Efficacy and Safety of Amyloid Depleter ALXN2220 in Adult Participants with Transthyretin Amyloid Cardiomyopathy (ATTR-CM) - ALXN2220-ATTRCM-301

Start Date14 May 2024

Sponsor / Collaborator

Alexion Pharmaceuticals, Inc.

NCT06183931 / RecruitingPhase 3

A Phase 3, Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Efficacy and Safety of Amyloid Depleter ALXN2220 in Adult Participants With Transthyretin Amyloid Cardiomyopathy (ATTR-CM)

The primary objective of this study is to access the efficacy of ALXN2220 in the treatment of adult participants with ATTR-CM by evaluating the difference between the ALXN2220 and placebo groups as assessed by the total occurrences of ACM and CV clinical events.

Start Date11 Jan 2024

Sponsor / Collaborator

Alexion Pharmaceuticals, Inc.

100 Clinical Results associated with NI-006

100 Translational Medicine associated with NI-006

100 Patents (Medical) associated with NI-006

Literatures (Medical) associated with NI-006

01 Sep 2024·Current Opinion in Cardiology

Treatment of transthyretin cardiac amyloidosis

Review

Author: Maurer, Mathew S ; Wardhere, Abdirahman ; Bampatsias, Dimitrios

Purpose of reviewTafamidis is currently the only approved disease-modifying treatment for ATTR-CM. However, there have been important developments in the treatment of ATTR-CM, as the results of two phase 3 trials were published and several other trials are in their final stages. In this review, we summarize current and future therapies for ATTR-CM.Recent findingsRecently, acoramidis, a TTR stabilizer has been proven to be effective in reducing mortality and morbidity compared to placebo in the ATTRibute-CM trial. Additionally, patisiran, an RNA silencer, preserved functional capacity and quality of life compared to placebo in the APOLLO-B trial. However, the FDA declined to approve patisiran for ATTR-CM. The results of phase 1 trial of ALXN2220, an antiamyloid antibody raise hope for reversal of myocardial damage by amyloid depletion. Phase 3 trials evaluating the efficacy of different RNA silencers, gene editing with CRISPR-Cas9, and other anti-amyloid antibodies are ongoing.SummaryTherapies targeting different mechanism in the pathophysiology of ATTR-CM provide new alternatives for treating patients with ATTR-CM. Future research should focus on comparing their effectiveness, the potential of combined treatment with agents from different classes and on identifying the patients who will benefit most from each class of medication.

20 Jul 2023·New England Journal of MedicineQ1 · MEDICINE

Phase 1 Trial of Antibody NI006 for Depletion of Cardiac Transthyretin Amyloid

Q1 · MEDICINE

Article

Author: Mercuri, Michele F ; Lairez, Olivier ; Kristen, Arnt V ; Donal, Erwan ; Aus dem Siepen, Fabian ; van der Meer, Peter ; Hock, Christoph ; Garcia-Pavia, Pablo ; Grimm, Jan ; Michalon, Aubin ; Frost, Robert J A ; Nitsch, Roger M ; Kahr, Peter C ; Damy, Thibaud

BACKGROUNDTransthyretin amyloid (ATTR) cardiomyopathy is a progressive and fatal disease caused by misfolded transthyretin. Despite advances in slowing disease progression, there is no available treatment that depletes ATTR from the heart for the amelioration of cardiac dysfunction. NI006 is a recombinant human anti-ATTR antibody that was developed for the removal of ATTR by phagocytic immune cells.METHODSIn this phase 1, double-blind trial, we randomly assigned (in a 2:1 ratio) 40 patients with wild-type or variant ATTR cardiomyopathy and chronic heart failure to receive intravenous infusions of either NI006 or placebo every 4 weeks for 4 months. Patients were sequentially enrolled in six cohorts that received ascending doses (ranging from 0.3 to 60 mg per kilogram of body weight). After four infusions, patients were enrolled in an open-label extension phase in which they received eight infusions of NI006 with stepwise increases in the dose. The safety and pharmacokinetic profiles of NI006 were assessed, and cardiac imaging studies were performed.RESULTSThe use of NI006 was associated with no apparent drug-related serious adverse events. The pharmacokinetic profile of NI006 was consistent with that of an IgG antibody, and no antidrug antibodies were detected. At doses of at least 10 mg per kilogram, cardiac tracer uptake on scintigraphy and extracellular volume on cardiac magnetic resonance imaging, both of which are imaging-based surrogate markers of cardiac amyloid load, appeared to be reduced over a period of 12 months. The median N-terminal pro-B-type natriuretic peptide and troponin T levels also seemed to be reduced.CONCLUSIONSIn this phase 1 trial of the recombinant human antibody NI006 for the treatment of patients with ATTR cardiomyopathy and heart failure, the use of NI006 was associated with no apparent drug-related serious adverse events. (Funded by Neurimmune; NI006-101 ClinicalTrials.gov number, NCT04360434.).

World Journal of Cardiology

Recent advances in the diagnostic methods and therapeutic strategies of transthyretin cardiac amyloidosis

Author: Skoularigis, John ; Xanthopoulos, Andrew ; Magouliotis, Dimitrios E ; Kourek, Christos ; Giamouzis, Grigorios ; Briasoulis, Alexandros ; Georgoulias, Panagiotis ; Triposkiadis, Filippos

Cardiac amyloidosis is a progressive disease characterized by the buildup of amyloid fibrils in the extracellular space of the heart. It is divided in 2 main types, immunoglobulin light chain amyloidosis and transthyretin amyloidosis (ATTR), and ATTR amyloidosis is further divided in 2 subtypes, non-hereditary wild type ATTR and hereditary mutant variant amyloidosis. Incidence and prevalence of ATTR cardiac amyloidosis is increasing over the last years due to the improvements in diagnostic methods. Survival rates are improving due to the development of novel therapeutic strategies. Tafamidis is the only disease-modifying approved therapy in ATTR amyloidosis so far. However, the most recent advances in medical therapies have added more options with the potential to become part of the therapeutic armamentarium of the disease. Agents including acoramidis, eplontersen, vutrisiran, patisiran and anti-monoclonal antibody NI006 are being investigated on cardiac function in large, multicenter controlled trials which are expected to be completed within the next 2-3 years, providing promising results in patients with ATTR cardiac amyloidosis. However, further and ongoing research is required in order to improve diagnostic methods that could provide an early diagnosis, as well as survival and quality of life of these patients.

News (Medical) associated with NI-006

27 Aug 2024

·www.neurimmune.com

Long-term safety and efficacy of antibody ALXN2220 for depletion of cardiac ATTR to be presented at ESC Congress 2024

Neurimmune today announced that long-term safety and efficacy data from the open-label extension of a Phase I trial related to ALXN2220 (formerly NI006) for the treatment of transthyretin amyloid cardiomyopathy (ATTR-CM) will be presented in London at the ESC Congress 2024, a scientific congress of the European Society of Cardiology (ESC), on September 1, 17:48 UK time. Professor Peter van der Meer from the University Medical Centre Groningen, Netherlands, will present during the session for Advances in Amyloidosis. Presentation Details: Title: Long-term safety and efficacy of antibody ALXN2220 for depletion of cardiac amyloid transthyretin: Results of treatment beyond 12 months in the open-label extension of study NI006-101 Presenter: Peter van der Meer, MD, PhD, Cardiologist, University Medical Center Groningen (UMCG) Session: Advances in Amyloidosis Date: September 1, 2024 Time: 17:48 UK time Location: Science Box 1 Amyloid transthyretin cardiomyopathy (ATTR-CM) is increasingly recognized as a treatable cause of heart failure. Progressive ATTR amyloid depositions characterize the disease, leading to progressive heart failure and a high rate of fatality if left untreated. Despite recent advances in slowing disease progression, there is no treatment available to deplete cardiac ATTR amyloid and revert cardiac dysfunction. ALXN2220 is an investigational human monoclonal antibody designed to deplete amyloid deposits in ATTR-CM as add-on to standard of care.1,2 At the ESC Congress 2024, Neurimmune, Alexion, AstraZeneca Rare Disease and the clinical investigators will present new long-term safety, tolerability and efficacy data of ALXN2220 treatment beyond 12 months which was studied in a prolonged Open-Label Extension of the NI006-101 trial. Prof. Christoph Hock, Chief Medical Officer of Neurimmune, said: “The depletion of the cardiac ATTR amyloid deposits is a rational therapeutic target to revert disease pathology and restore organ function. Our data at ESC Congress 2024 underscores the commitment of Neurimmune and our partner Alexion to evaluate the safety and efficacy of longer-term ALXN2220 treatment to develop a best-in-class option for patients with ATTR-CM and to increase our understanding of the mechanisms underlying amyloid depletion.” In 2022, Neurimmune entered into an exclusive global collaboration and license agreement with Alexion, AstraZeneca Rare Disease, for ALXN2220. Neurimmune is responsible for completion of the Phase 1b clinical study on behalf of Alexion, with Alexion incurring certain trial costs. Aside from the Phase 1b trial, Alexion is responsible for further clinical development, manufacturing, and commercialization as ALXN2220. In 2024, Alexion initiated the Phase 3 DepleTTR-CM clinical study to assess the efficacy and safety of ALXN2220 for the treatment of ATTR-CM. 1Garcia-Pavia et al., N Engl J Med 2023; 389(3):239. 2Michalon et al., Nat Commun 2021; 12(1):3142. Neurimmune is a biopharmaceutical company translating human immune memory into antibody therapeutics. Neurimmune develops drug candidates for CNS and related protein aggregation diseases including Alzheimer’s disease, amyotrophic lateral sclerosis, frontotemporal dementia and ATTR cardiomyopathy. With its Reverse Translational MedicineTM technology, Neurimmune discovered the brain amyloid depleter NI101SQ for Alzheimer’s disease, anti-SOD1 antibody AP-101 for ALS and the anti-ATTR antibody ALXN2220 (formerly NI006) for ATTR cardiomyopathy, programs being currently evaluated in clinical trials. John Capodanno (US) john.capodanno@dentonsglobaladvisors.com Martin Meier-Pfister (Switzerland) media@neurimmune.com

Phase 1License out/inPhase 3

23 May 2024

·www.neurimmune.com

Multiple Poster Presentations on ALXN2220 for Cardiac ATTR Amyloid Depletion to be Presented at the XIX International Symposium on Amyloidosis

Neurimmune today announced that three poster presentations related to ALXN2220 (formerly NI006) for the treatment of transthyretin amyloid cardiomyopathy (ATTR-CM) will be presented by Neurimmune, our partners Alexion, AstraZeneca Rare Disease and our clinical investigators in Rochester, Minnesota at the XIX International Symposium on Amyloidosis, a scientific congress of the International Society of Amyloidosis (ISA). ALXN2220 is an investigational human monoclonal antibody designed to deplete amyloid deposits in ATTR-CM as add-on to standard of care.1,2 High-resolution live-cell imaging data presented will offer new insight into the underlying cellular mechanism of antibody-mediated amyloid removal with ALXN2220. Results will show the addition of ALXN2220 to ATTR patient-derived cardiac tissue triggered phagocytosis, including recruitment of macrophages to amyloid deposits, detachment, internalization and degradation of ATTR amyloid. An encore poster presentation will report results from the first-in-human study of ALXN2220. Initial treatment with ALXN2220 was well tolerated with a transient increase in C-reactive proteins, suggesting initial targeted immune activation and recruitment of phagocytic immune cells. Additionally, an encore poster presentation will describe the pharmacokinetic and pharmacodynamic (PK/PD) model used for the selection of the dose range, dose escalation, dosing interval and study duration. Presentation Details Title: ALXN2220: high-resolution live-cell imaging of antibody-mediated cardiac ATTR amyloid depletion Presenter: Aubin Michalon, Director Amyloidosis & Preclinical Development, Neurimmune Date: May 28, 2024 Poster ID: PBI (#226) Title: ALXN2220: targeted immune activation in patients undergoing antibody-mediated cardiac ATTR amyloid depletion Presenter: Fabian aus dem Siepen, University Hospital Heidelberg Date: May 29, 2024 Poster ID: PC116 (#227) Title: Prediction of cardiac ATTR depletion by NI006 using mechanistic PK/PD modeling Presenter: Aubin Michalon, Director Amyloidosis & Preclinical Development, Neurimmune Date: May 29, 2024 Poster ID: PC123 (#291) Amyloid transthyretin cardiomyopathy (ATTR-CM) is an underdiagnosed, systemic condition that leads to progressive heart failure and high rate of fatality within four years from diagnosis.3,4 Progressive ATTR amyloid depositions characterize the disease, causing heart failure and death. Despite recent advances and approved therapies, there remains significant unmet medical need in treating moderate to severe ATTR-CM, and amyloid depletion may constitute an important new mechanism to achieve further effectiveness. In 2022, Neurimmune entered into an exclusive global collaboration and license agreement with Alexion, AstraZeneca Rare Disease, for ALXN2220. Neurimmune is responsible for completion of the Phase 1b clinical study on behalf of Alexion, with Alexion incurring certain trial costs. Aside from the Phase 1b trial, Alexion is responsible for further clinical development, manufacturing, and commercialization of ALXN2220. In 2024, Alexion initiated the Phase 3 DepleTTR-CM clinical study to assess the efficacy and safety of ALXN2220 for the treatment of ATTR-CM. 1Garcia-Pavia et al., N Engl J Med 2023; 389(3):239. 2Michalon et al., Nat Commun 2021; 12(1):3142. 3 Lauppe RE, et al. Open Heart. 2021 Oct;8(2):e001755. 4 González-Duarte A, et al. Neurol Ther. 2020;9(1):135-149. Neurimmune is a biopharmaceutical company translating human immune memory into antibody therapeutics. Neurimmune develops drug candidates for CNS and related protein aggregation diseases including Alzheimer’s disease, amyotrophic lateral sclerosis, frontotemporal dementia and ATTR cardiomyopathy. Neurimmune discovered NI101SQ, a human monoclonal antibody to deplete brain amyloid of patients with Alzheimer’s disease. With its Reverse Translational MedicineTM technology, Neurimmune discovered the anti-SOD1 antibody AP-101 for ALS and the anti-ATTR antibody NI006 for ATTR cardiomyopathy, programs being currently evaluated in clinical trials. John Capodanno (US) john.capodanno@dentonsglobaladvisors.com Martin Meier-Pfister (Switzerland) media@neurimmune.com

License out/inPhase 1Immunotherapy

23 May 2024

·www.biospace.com

AstraZeneca demonstrates commitment to patients living with amyloidosis at the 2024 International Symposium on Amyloidosis (ISA)

Additional clinical and real-world data from the industry’s largest amyloidosis pipeline will advance understanding of underlying mechanisms of disease and unmet needs WILMINGTON, Del.--(BUSINESS WIRE)-- AstraZeneca and Alexion, AstraZeneca Rare Disease, will showcase 14 studies, including real-world evidence (RWE), from their portfolio and pipeline of investigational amyloidosis therapies at the International Symposium on Amyloidosis (ISA), in Rochester, MN from May 26–30, 2024. Presentations will include a new subgroup analyses of the Phase 3 NEURO-TTRansform study of WAINUATM (eplontersen), which was approved by the US Food and Drug Administration (FDA) in December 2023 for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults, commonly referred to as hATTR-PN or ATTRv-PN.1 Additionally, clinical data will be presented on ALXN2220 and anselamimab, which are being evaluated in Phase III clinical trials for ATTR and light chain (AL) amyloidosis, respectively. Sarah Walters, Vice President, US Cardiovascular, Renal & Metabolic Diseases, AstraZeneca, said: “AstraZeneca is dedicated to advancing the science and improving the lives of patients that are impacted by this devastating disease. Our data at the 2024 International Symposium on Amyloidosis demonstrate the leadership commitment AstraZeneca, Alexion and our partners Ionis and Neuroimmune have to develop best in class treatment options to serve a broad range of amyloidosis patients.” Christophe Hotermans, Senior Vice President, Head of Global Medical Affairs, Alexion, said: “With the largest and fastest-growing pipeline of investigational amyloidosis therapies, we are working to advance multiple modalities with the potential to halt, reduce or reverse organ damage. Key presentations at the ISA Annual Meeting include live-cell imaging and Phase I clinical data evaluating the ability of ALXN2220 to remove amyloid from cardiac tissue, to support its further study as a potential treatment for advanced ATTR cardiomyopathy. Additionally, findings on epidemiology and patient renal outcomes will reinforce the urgency for differentiated amyloidosis diagnosis and additional treatment options in AL amyloidosis.” Robust evidence program increases understanding of amyloidosis patient characteristics and treatment effectiveness. In addition to sub-analyses of the NEURO-TTRansform data, AstraZeneca will present US patient characteristics data, preliminary data from the OverTTuRe study measuring prevalence and characteristics of phenotypes in patients with ATTR amyloidosis in the United States and Japan; as well as the MaesTTRo study design, part of a global, multi-study, real-world evidence program designed to fill the evidence gaps of the effectiveness of treatments for ATTR. WAINUA is currently being evaluated in the Phase 3 CARDIO-TTRansform study for adults with cardiomyopathy of transthyretin-mediated amyloidosis (ATTR-CM), a systemic, progressive and fatal condition that typically leads to progressive heart failure and often death within three-to-five years from disease onset.2-5 The CARDIO-TTRansform Phase 3 study is fully enrolled with more than 1,400 patients–making it the largest study in this patient population to date.6 As part of a global development and commercialization agreement, AstraZeneca and Ionis are commercializing WAINUA for the treatment of hATTR-PN in the US and are seeking regulatory approval in Europe and other parts of the world.6 Novel investigational amyloid depleter assets demonstrate potential to improve outcomes for amyloidosis patients High-resolution live-cell imaging will offer new insight into the underlying cellular mechanism of antibody-mediated amyloid removal with ALXN2220. Results will show the addition of ALXN2220 to ATTR patient-derived cardiac tissue triggered phagocytosis, including recruitment of macrophages to amyloid deposits, detachment, internalization and degradation of ATTR amyloid. An encore poster presentation will report results from the first-in-human study of ALXN2220. Initial treatment with ALXN2220 was well tolerated with a transient increase in C-reactive proteins, suggesting initial targeted immune activation and recruitment of phagocytic immune cells. Additionally, an encore poster presentation will describe the pharmacokinetic and pharmacodynamic (PK/PD) model used for the selection of the dose range, dose escalation, dosing interval and study duration. Further, a poster will outline the baseline demographics and characteristics of the 406 participants of the Alexion CARES clinical program evaluating anselamimab in patients with Mayo Stage IIIa and IIIb AL amyloidosis, which includes the largest prospective AL amyloidosis study to date in advanced stage AL amyloidosis. Advancing understanding of the amyloidosis landscape A retrospective chart analysis from the US EMR TriNetX database will report outcomes in AL amyloidosis patients with renal involvement receiving bortezomib or daratumumab. Only half of patients were renal-responders and few achieved renal complete response (renCR, proteinuria ≤200 mg/day), underscoring the unmet medical need for this patient subset. Retrospective analyses will also be presented across three posters on the incidence and prevalence of AL and ATTR amyloidosis, reinforcing the importance of timely diagnosis of amyloidosis and continued monitoring. A comprehensive list of AstraZeneca key abstracts to be presented at the 2024 International Symposium on Amyloidosis includes7: Lead author Abstract title Presentation details Poster presentation session 1: 10:00-10:30 Poster presentation session 2: 14:45-15:45 Eplontersen Gillmore JD, Davis M, Hahn K, Smith G, Shivappa N, Papas M, Folkvaljon F, Pao C, Sundin AK, L Wittbrodt E, Grogan M Prospective, Real-World Data on the Characteristics, Treatment Patterns, and Outcomes of Patients With Transthyretin Amyloidosis: Design of the MaesTTRo Study Date: Wednesday, May 29 Abstract ID: 204 Waddington Cruz M, Berk J, Parman Y, Gertz M, Khella S, Weiler M, Kwoh J, Chen J, Reicher B, Nåtman J, Dasgupta N Eplontersen for Hereditary Transthyretin Amyloidosis With Polyneuropathy: An Exploratory Analysis of Treatment Effect in Male and Female Patients Date: Wednesday, May 29 Abstract ID: 202 Gillmore JD, Adams D, Weiler M, Masri A, Obici L, Kwoh J, Reicher B, Chen J, Waddington Cruz M, Natman J, Gertz M Eplontersen for Hereditary Transthyretin Amyloidosis With Polyneuropathy: An Exploratory Analysis in Patients With the V30M TTR variant and Early-onset or Late-onset Disease Date: Wednesday, May 29 Abstract ID: 230 Wixner J, Conceição I, Berk J, Adams D, Polydefkis M, Attarian S, Gillmore J, Dyck J, Coelho T, Chen J, Hardy E, Kwoh J, Nåtman J, Waddington Cruz M Neuropathy Impairment and Nutritional Status With Eplontersen in Patients With Hereditary Transthyretin-Mediated Amyloidosis Date: Wednesday, May 29 Abstract ID: 174 Alexander K, Alvarez C, Kumar N, Pao C, Wittbrodt E, Kohsaka S Prevalence and Descriptive Characteristics of Clinical Phenotypes in Patients With ATTR amyloidosis in the United States and Japan: Preliminary Results from the OverTTuRe Study Date: Monday, May 27 Abstract ID: 198 Bazell C, Alston M, Kumar N, Huang J, Venditto J, Grillis D, Eisenberg S, Nativi-Nicolau J Descriptive Characteristics of Patients Diagnosed With Transthyretin Amyloidosis in the Commercial and Medicare Populations Date: Wednesday, May 29 Abstract ID: 518 ALXN 2220 Michalon A, Huy, Mercuri M, Kahr P, Hock C, Grimm J ALXN2220: High-resolution Live-cell Imaging of Antibody-mediated Cardiac ATTR Amyloid Depletion Date: Tuesday, May 28 Abstract ID: 226 Michalon A, Renaud L, Machacek M, Cortijo C, Udaata C, Mercuri M, Buller F, Hock C, Nitsch R, Kahr P, Grimm J Prediction of Cardiac ATTR Depletion by NI006 Using Mechanistic PK/PD Modeling Date: Wednesday, May 29 Abstract ID: 291 Aus dem Siepen F, Van der Meer P, Damy T, Garcia-Pavia P, Donal E, Lairez O, Blank A, Kristen A, Quarta CC, Buchele G, Mercuri M, Hock C, Michalon A, Kahr P, Rey S, Tichy M ALXN2220: Targeted Immune Activation in Patients Undergoing Antibody-mediated Cardiac ATTR Amyloid Depletion Date: Wednesday, May 29 Abstract ID: 227 Amyloidosis Incidence and Analyses Laires PA, Evans J, Thompson J, Manwani R, Mudumby P, Field M, Fang S Prevalence, Incidence, and Characterization of Light Chain Amyloidosis in the USA: A Real-World Analysis Utilizing Electronic Health Records (EHR) Date: Monday, May 27 Abstract ID: 65 Manwani R, Yang F, Zhang Y, Laires PA Outcomes in Patients With AL Amyloidosis With Renal Involvement: Findings from the TriNetX Database Date: Monday, May 27 Abstract ID: 113 Laires PA, Li SXL, Uday A, Kumar P, Silva AM, Quarta C Prevalence and Incidence of ATTR Amyloidosis in the United States: Insights from Claims Database and Electronic Health Records Date: Tuesday, May 28 Abstract ID: 68 Laires PA, Zhang Y, Manwani R, Silva AM, Catini J, Thompson J, Dozier M, Yang F Subtype Distribution of Amyloidosis in the United States: Insights from an Electronic Health Records Database Analysis Date: Tuesday, May 28 Abstract ID: 112 The full list of ISA 2024 congress abstracts are available online. INDICATION for WAINUATM (eplontersen) WAINUA injection, for subcutaneous use, 45 mg is indicated for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults. IMPORTANT SAFETY INFORMATION for WAINUATM (eplontersen) WARNINGS AND PRECAUTIONS Reduced Serum Vitamin A Levels and Recommended Supplementation WAINUA leads to a decrease in serum vitamin A levels. Supplement with recommended daily allowance of vitamin A. Refer patient to an ophthalmologist if ocular symptoms suggestive of vitamin A deficiency occur. ADVERSE REACTIONS Most common adverse reactions (≥9% in WAINUA-treated patients) were vitamin A decreased (15%) and vomiting (9%). Please see link to US Full Prescribing Information for WAINUA. Notes NEURO-TTRansform NEURO-TTRansform is a global, open-label, randomized trial evaluating the efficacy and safety of eplontersen in patients with hATTR-PN.8,9 The trial enrolled adult patients with hATTR-PN Stage 1 or Stage 2 compared to the external placebo group from the NEURO-TTR registrational trial that Ionis completed in 2017.8,9 The comparison of efficacy and safety for WAINUA versus external placebo was based on data up to week 66, and all patients were followed on treatment until week 85, when they had the option to transition into an open-label extension study, which is still ongoing.8,9 WAINUA WAINUATM (eplontersen) is a ligand-conjugated antisense oligonucleotide (LICA) medicine designed to reduce the production of transthyretin, or TTR protein.9,10 WAINUA has been approved in the US for the treatment of the polyneuropathy of hereditary transthyretin-mediated amyloidosis in adults (also referred to as hATTR-PN).1 AstraZeneca in amyloidosis Amyloidosis is a group of complex rare diseases caused by abnormal proteins that misfold and clump together to form toxic amyloids that deposit in tissues or organs, including the heart, kidneys and peripheral nerves.11-12 The build-up of these toxic amyloids can result in significant organ damage and organ failure that can severely impact quality of life and ultimately be fatal.11-12 AstraZeneca and its Rare Disease Unit, Alexion, are developing and evaluating multiple modalities with the potential to halt and reduce organ damage across various types of amyloidosis. The Company is uniquely positioned to lead therapeutic and diagnostic advances for people living with amyloidosis with the largest and fastest-growing pipeline of investigational amyloidosis therapies to address the spectrum of patient needs. Alexion Alexion, AstraZeneca Rare Disease, is focused on serving patients and families affected by rare diseases and devastating conditions through the discovery, development and delivery of life-changing medicines. A pioneering leader in rare disease for more than three decades, Alexion was the first to translate the complex biology of the complement system into transformative medicines, and today it continues to build a diversified pipeline across disease areas with significant unmet need, using an array of innovative modalities. As part of AstraZeneca, Alexion is continually expanding its global geographic footprint to serve more rare disease patients around the world. It is headquartered in Boston, MA, US. 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 and follow us on social media @AstraZeneca. References WAINUATM (eplontersen) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2023. Viney N, et al. Ligand conjugated antisense oligonucleotide for the treatment of transthyretin amyloidosis: preclinical and phase 1 data. ESC Heart Failure. 2021;8:652-661. Rintell D, et al. Patient and family experience with transthyretin amyloid cardiomyopathy (ATTR-CM) and polyneuropathy (ATTR-PN) amyloidosis: results of two focus groups. Orphanet J Rare Dis. 2021;16:70. Columbia University Irving Medical Center [Internet]. Drug Reduces Death from Underdiagnosed Form of Heart Failure [last accessed 11 December 2023]. Available from: . ClinicalTrials.gov. 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) [last accessed 21 May 2024] Available from: . Ionis Pharmaceuticals [Internet]. WAINUA™ (eplontersen) granted regulatory approval in the U.S. for the treatment of adults with polyneuropathy of hereditary transthyretin-mediated amyloidosis [last accessed 16 May 2024]. Available from: . Mayo Clinic. International Symposium on Amyloidosis: Abstracts/Posters [last accessed 21 May 2024] Available from: . 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. Nerol Ther. 2021 Jun;10(1):375-389. Coelho T, et al. Eplontersen for Hereditary Transthyretin Amyloidosis With Polyneuropathy. JAMA. 2023;330(15):1448–1458. 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;12:267–287. Cleveland Clinic. Amyloidosis. Cleveland Clinic website. Accessed May 21, 2024. . Mayo Clinic. Amyloidosis. Mayo Clinic website. Accessed May 21, 2024. . US-89473 Last Updated 5/24

Phase 3Clinical ResultPhase 1Drug Approval

100 Deals associated with NI-006

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Transthyretin Amyloid Cardiomyopathy	Phase 3	NL	Alexion Pharmaceuticals, Inc.	11 Jan 2024
Transthyretin Amyloid Cardiomyopathy	Phase 3	SE	Alexion Pharmaceuticals, Inc.	11 Jan 2024
Transthyretin Amyloid Cardiomyopathy	Phase 3	KR	Alexion Pharmaceuticals, Inc.	11 Jan 2024
Transthyretin Amyloid Cardiomyopathy	Phase 3	CN	Alexion Pharmaceuticals, Inc.	11 Jan 2024
Transthyretin Amyloid Cardiomyopathy	Phase 3	DK	Alexion Pharmaceuticals, Inc.	11 Jan 2024
Transthyretin Amyloid Cardiomyopathy	Phase 3	ES	Alexion Pharmaceuticals, Inc.	11 Jan 2024
Transthyretin Amyloid Cardiomyopathy	Phase 3	AT	Alexion Pharmaceuticals, Inc.	11 Jan 2024
Transthyretin Amyloid Cardiomyopathy	Phase 3	IT	Alexion Pharmaceuticals, Inc.	11 Jan 2024
Transthyretin Amyloid Cardiomyopathy	Phase 3	JP	Alexion Pharmaceuticals, Inc.	11 Jan 2024
Transthyretin Amyloid Cardiomyopathy	Phase 3	BE	Alexion Pharmaceuticals, Inc.	11 Jan 2024

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04360434 (NI006-101, Literature) Manual	Phase 1	Transthyretin Amyloid Cardiomyopathy	40	NI006	(tcapsmggow) = The use of NI006 was associated with no apparent drug-related serious adverse events. chnsqtlpxk (wjhurcufcj )	Positive	30 Jul 2023
				placebo

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis