cliramitug (ALXN2220) / Neurimmune, AstraZeneca - LARVOL DELTA

The importance of distinct cardiac MRI regional analyses to assess the effects of cliramitug on amyloid depletion from the Phase 1b study NI006-101 (ESC 2026) - "Serial cardiac MRIs were performed in a subset of participants according to participating sites and analyzed centrally in this post hoc analysis. 15 patients (all male, median age 68 years, 33% ATTRv, 94% on baseline tafamidis, median LVEF 51.4%) were followed longitudinally with a median of 4 post-baseline cardiac MRIs over a median study duration of 28 months. In this post hoc MRI analysis, treatment initiation with cliramitug up to approximately 30 g cumulative dose was associated with reduced ECV and wall thickness across all regions of the LV. Radial strain emerged as a potential indicator of improved systolic function. These observations provide additional insights into the regional effects of amyloid depleting therapy in ATTR-CM, and support the further development of cliramitug."

P1 data • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Heart Failure • Hypertrophic Cardiomyopathy

DepleTTR-CM: Study of ALXN2220 Versus Placebo in Adults With ATTR-CM (clinicaltrials.gov) - P3 | N=1181 | Active, not recruiting | Sponsor: Alexion Pharmaceuticals, Inc. | Trial completion date: Oct 2027 ➔ Apr 2028 | Trial primary completion date: Jun 2027 ➔ Dec 2027

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

ATTRiumph: A Study to Evaluate the Efficacy and Safety of Concomitant Use of Eplontersen and ALXN2220 Compared With Eplontersen and Placebo for Adults Participants With ATTR-CM (clinicaltrials.gov) - P2 | N=326 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting

Enrollment closed • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

Cliramitug for depletion of cardiac amyloid transthyretin: long-term follow-up of the NI006-101 trial. (PubMed, Nat Med) - P1 | "Twenty-three participants (20 receiving background treatment with tafamidis, all male) entered OLE2 and received a median of 10 additional infusions, increasing the maximum total exposure to 24 infusions and extending the median follow-up to 29.3 months. These time- and dose-dependent improvements across structural, functional and biomarker endpoints support the therapeutic potential of amyloid-depleting therapy with cliramitug in ATTR-CM. ClinicalTrials.gov: NCT04360434 ."

First-in-human • Journal • Cardiomyopathy • Cardiovascular

ATTRiumph: A Study to Evaluate the Efficacy and Safety of Concomitant Use of Eplontersen and ALXN2220 Compared With Eplontersen and Placebo for Adults Participants With ATTR-CM (clinicaltrials.gov) - P2 | N=326 | Recruiting | Sponsor: AstraZeneca | Not yet recruiting ➔ Recruiting

Enrollment open • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

Transthyretin Amyloidosis (ATTR) Cases from Turkiye and insights from a Nephrology Perspective (ERA 2026) - "Tafamidis (61 mg daily) was initiated in every case; one patient subsequently entered a phase ‑ 3 trial of an amyloid ‑ depleting agent (ALXN2220). Why this case is exeptional This case series is exceptional because it brings attention to renal involvement in transthyretin amyloidosis, a frequently overlooked aspect of the disease, likely reported for the first time in Türkiye. Image Periorbital ecchymosis in a ATTR patient"

Clinical • Amyloidosis • Atrial Fibrillation • Cardiac Amyloidosis • Cardiomyopathy • Chronic Kidney Disease • Heart Failure • Hypotension • Nephrology • Renal Calculi • CST3

ATTRiumph: A Study to Evaluate the Efficacy and Safety of Concomitant Use of Eplontersen and ALXN2220 Compared With Eplontersen and Placebo for Adults Participants With ATTR-CM. (clinicaltrials.gov) - P2 | N=326 | Not yet recruiting | Sponsor: AstraZeneca

New P2 trial • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

Study of Re-Treatment With ALXN2220 in Patients With ATTR-CM (clinicaltrials.gov) - P2 | N=35 | Active, not recruiting | Sponsor: Neurimmune AG | Recruiting ➔ Active, not recruiting

Enrollment closed • Amyloidosis • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

Study of Re-Treatment With ALXN2220 in Patients With ATTR-CM (clinicaltrials.gov) - P2 | N=35 | Recruiting | Sponsor: Neurimmune AG

New P2 trial • 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) - " Out of 39 potentially eligible participants who completed the placebo-controlled period, 38 patients chose to participate in the open-label extension (all were male, median age 72 years, 84% ATTRwt, 89% on tafamidis). Continued treatment with ALXN2220 was well-tolerated during the open-label extension of study NI006-101 up to a total of 24 administrations. Compliance to study drug administrations was high and musculoskeletal complaints appeared to decrease in frequency and severity with continued treatment. No episodes of platelet reductions were observed."

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

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) - " In total, 46 patients were enrolled in the study (85% ATTRwt, median age 73 years, 89% on baseline tafamidis). Treatment with ALXN2220 at doses of 30 to 60 mg/kg q4w was associated with improvements in echocardiographic parameters of ventricular function and cardiac structure compared to baseline. Together with the observed changes in scintigraphic and MRI measures of amyloid load and cardiac biomarkers, these data indicate that ATTR depletion via ALXN2220 may improve cardiac structure and function."

Clinical • Cardiac Amyloidosis • Cardiomyopathy • Cardiovascular

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

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