NI006 / Neurimmune, AstraZeneca - LARVOL DELTA

DepleTTR-CM: Study of ALXN2220 Versus Placebo in Adults With ATTR-CM (clinicaltrials.gov) - P3 | N=1000 | Active, not recruiting | Sponsor: Alexion Pharmaceuticals, Inc. | Recruiting ➔ Active, not recruiting | Trial completion date: Oct 2028 ➔ Oct 2027 | Trial primary completion date: Jul 2028 ➔ Jun 2027

Enrollment closed • Trial completion date • Trial primary completion date • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

Tolerability of continued treatment with ATTR depleter ALXN2220 in the open-label extension of Phase 1 study NI006-101 (ESC-WCC 2025) - No abstract available

Clinical • P1 data • Cardiovascular • Congestive Heart Failure • Heart Failure

Echocardiographic assessments of ventricular function and cardiac structure with ALXN2220, an ATTR depleter: analysis from the open-label extension of study NI006-101 (ESC-WCC 2025) - No abstract available

Clinical • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

Pharmacological Management of Transthyretin Amyloid Cardiomyopathy: Where We Are and Where We Are Going. (PubMed, J Clin Med) - "TTR stabilizers, such as tafamidis and acoramidis, can reduce TTR instability and subsequent amyloid fibril formation...Gene-silencing therapies using small interfering RNAs (siRNAs), such as patisiran and vutrisiran, or antisense oligonucleotide inhibitors (ASOs), such as inotersen and eplontersen, serve as powerful therapeutic options by decreasing TTR production; trials on patients with ATTR-CM have been recently published or are ongoing. Novel, emerging therapies aim to enhance fibril clearance using monoclonal antibodies, such as NI006, that target amyloid deposits in the myocardium, promoting their depletion, plausibly with regression of the structural and functional impairments caused by the disease...Future directions will involve improving patients' screening to achieve earlier diagnoses, optimising patients' selection for disease-modifying therapy and identifying criteria for the treatment's response or lack thereof to possibly consider therapy..."

Journal • Review • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure

Antibody ALXN2220 (Formerly NI006) for the Treatment of Transthyretin Cardiac Amyloidosis. (PubMed, Cardiol Rev) - "The agents currently approved by the United States Food and Drug Administration-tafamidis and acoramidis-are transthyretin stabilizers that prevent the breakdown of the physiologic transthyretin tetramer into fibril-forming monomers. A multinational, placebo-controlled phase 3 trial (DepleTTR-CM) is ongoing to assess long-term efficacy, functional outcomes, and survival impact. These results are expected to provide critical real-world evidence on ALXN2220's role in transthyretin cardiac amyloidosis management."

Journal • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure

EVALUATING A MEDICALLY TRAINED ARTIFICIAL INTELLIGENCE AND NATURAL LANGUAGE PROCESSING-ENABLED, LARGE-LANGUAGE MODEL IN SCREENING FOR TRANSTHYRETIN CARDIAC AMYLOIDOSIS CLINICAL TRIALS - Trejeeve Martyn (ACC 2025) - "We sought to evaluate the speed, accuracy, and yield of utilizing a medically-trained large language model (LLM), Synapsis AI, deployed within a large integrated health system in pre-screening patients for a cardiac amyloidosis clinical trial. Eligibility for DepleTTR-CM, a phase 3 study evaluating the efficacy and safety of the amyloid depleter ALXN2220 in amyloidosis cardiomyopathy (ATTR-CM) was assessed... Use of a medically-trained LLM demonstrated significant potential for rapid, enhanced, and accurate patient recruitment for studies involving rare cardiomyopathies."

Clinical • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

New therapies to treat cardiac amyloidosis. (PubMed, Curr Opin Cardiol) - "The therapeutic landscape for ATTR-CM and AL-CM is rapidly evolving, driven by novel therapies targeting diverse mechanisms. Ongoing clinical trials promise to further refine the standard of care and improve outcomes for patients with cardiac amyloidosis."

Journal • Amyloidosis • Cardiac Amyloidosis • Cardiovascular

Prediction of Cardiac ATTR Depletion by NI006 (ALXN2220) Using Mechanistic PK/PD Modeling. (PubMed, Clin Pharmacol Ther) - "These predictions were in good agreement with the observed primary results of the clinical phase Ib study where amyloid burden was measured by imaging. This novel translational PK/PD model provided important predictions to guide the design of the phase Ib study of NI006, indicating the value of this approach to integrate preclinical results into clinical trial design and increase translational success."

Journal • PK/PD data • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure

Structural Basis for Monoclonal Antibody Therapy for Transthyretin Amyloidosis. (PubMed, Pharmaceuticals (Basel)) - "Aiding these recent achievements has been the remarkable ability of cryo-electron microscopy (EM) to determine high-resolution structures of amyloid fibrils obtained from individual patients. Here, we will examine the cryo-EM structures of transthyretin amyloid fibrils to explore the structural basis of the two monoclonal antibody therapies for ATTR that are in clinical trials, ALXN-2220 and Coramitug, as well as to point out potential applications of this approach to other systemic amyloid diseases."

Journal • Review • Amyloidosis • Cardiac Amyloidosis

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 (ESC 2024) - "Up-titration and long-term treatment at a dose level of 30 mg/kg in the OLE was safe and well tolerated, with overall good adherence to treatment. Cardiac imaging and cardiac biomarker data indicated continued treatment effects beyond 12 months and supported the up-titration of patients to 30 mg/kg."

Clinical • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

Recent advances in the diagnostic methods and therapeutic strategies of transthyretin cardiac amyloidosis. (PubMed, World J Cardiol) - "Tafamidis is the only disease-modifying approved therapy in ATTR amyloidosis so far. 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."

Journal • Amyloidosis • Cardiac Amyloidosis • Cardiovascular

AstraZeneca demonstrates commitment to patients living with amyloidosis at the 2024 International Symposium on Amyloidosis (ISA) (Businesswire) - P1 | N=46 | NCT04360434 | Sponsor: Neurimmune AG | "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..."

Clinical • P1 data • Amyloidosis • Cardiomyopathy • CNS Disorders

DepleTTR-CM: Study of ALXN2220 Versus Placebo in Adults With ATTR-CM (clinicaltrials.gov) - P3 | N=1000 | Recruiting | Sponsor: Alexion Pharmaceuticals, Inc. | Trial primary completion date: Aug 2025 ➔ Jul 2028

Trial primary completion date • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

A poster from #HeartFailure2024 showing safety and details of immune activation of ALXN2220 in patients with ATTR-CM (previously NI006, now enrolling in the phase III DepleteTTR trial) CRP increases, but no increase in cytokines or complement activation. No severe adverse events directly related to treatment #CardioTwitter #Amyloidosis

Clinical data

Prediction of cardiac ATTR depletion by ALXN2220 using mechanistic PK/PD modeling (HEART FAILURE 2024) - "This novel mechanistic PK/PD model provided valuable estimates to guide the design of the first study of ALXN2220 in ATTR-CM. Model results were instrumental in the selection of the dose range, dosing interval and study duration. Overall, model predictions were consistent with the study results, indicating the value of a comprehensive integration of non-clinical data into clinical trial design to increase translational success."

PK/PD data • Cardiovascular

Initial safety of targeted immune activation with the amyloid depleter ALXN2220 (HEART FAILURE 2024) - "No acute severe or serious electrocardiographic or echocardiographic alterations were observed in relation to treatment with ALXN2220. Transient increases in CRP at higher doses may be consistent with an initial targeted immune activation by ALXN2220 upon binding to ATTR amyloid deposits and recruitment of phagocytic immune cells, but were no longer observed in the OLE phase."

Clinical • Cardiovascular • Congestive Heart Failure • Heart Failure • CXCL8 • IL6

A poster from hashtag#HeartFailure2024 showing safety and details of immune activation of ALXN2220 in patients with ATTR-CM (previously NI006, now enrolling in the phase III DepleteTTR trial) CRP increases, but no increase in cytokines or complement activation. No severe adverse events directly related to treatment hashtag#AMYLOIDOSIS (LinkedIn)

Clinical

Treatment of transthyretin cardiac amyloidosis. (PubMed, Curr Opin Cardiol) - "Therapies 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."

Journal • Amyloidosis • Cardiac Amyloidosis • Cardiovascular

DepleTTR-CM: Study of ALXN2220 Versus Placebo in Adults With ATTR-CM (clinicaltrials.gov) - P3 | N=1000 | Recruiting | Sponsor: Alexion Pharmaceuticals, Inc. | Not yet recruiting ➔ Recruiting | Trial completion date: Oct 2028 ➔ Jul 2028 | Trial primary completion date: Oct 2028 ➔ Oct 2025

Enrollment open • Trial completion date • Trial primary completion date • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

DepleTTR-CM: Study of ALXN2220 Versus Placebo in Adults With ATTR-CM (clinicaltrials.gov) - P3 | N=1000 | Not yet recruiting | Sponsor: Alexion Pharmaceuticals, Inc.

New P3 trial • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

Mathematical Modeling Predicts Treatment Efficacy in Transthyretin Cardiac Amyloidosis (AHA 2023) - "The secondary mechanism of diflusinil did not change equilibrium behavior compared to tafamidis. MEC values and time to clearance at MEC were lowest for NI006 (14.7%; 65 days) and doxycycline (16.1%; 36 months)... This mathematical model predicts ATTR clearance by four distinct mechanisms of action. The novel anti-ATTR antibody NI006 is a promising treatment with predicted faster onset and higher effectiveness for clearance of ATTR fibrils from the myocardium. This model can evaluate future treatment strategies and therapeutic targets."

Clinical • Amyloidosis • Cardiac Amyloidosis • Cardiovascular • CLU

First-in-Human Study of NI006 in Patients With Amyloid Transthyretin Cardiomyopathy (clinicaltrials.gov) - P1 | N=46 | Completed | Sponsor: Neurimmune AG | Active, not recruiting ➔ Completed | Trial completion date: Nov 2023 ➔ Jul 2023

Trial completion • Trial completion date • Cardiomyopathy • Cardiovascular

Antibody NI006 for Cardiac Transthyretin Amyloid Depletion. (PubMed, N Engl J Med) - No abstract available

Journal • Amyloidosis

Antibody NI006 for Cardiac Transthyretin Amyloid Depletion. Reply. (PubMed, N Engl J Med) - No abstract available

Journal • Amyloidosis

"【Heart Failure 2023】フェーズ1b試験より、トランスサイレチン型心アミロイドーシス（ATTR-CM）の慢性心不全患者において、抗ATTR抗体NI006の安全性は良好で、イメージングやバイオマーカーの変化からはATTRの除去が示唆されたことが発表された。https://t.co/tBkBRRkZuY #HeartFailure2023" (@tcross_news)

Cardiovascular • Congestive Heart Failure • Dyslipidemia • Heart Failure