One year follow up analysis of the phase 1a/b study of chimeric fibril-reactive monoclonal antibody 11-1F4 in patients with AL amyloidosis

Edwards, Camille V; Bhutani, Divaya; Mapara, Markus Y.; Shames, Sofia; Maurer, Mathew S.; Leng, Siyang; Wall, Jonathan S.; Solomon, Alan; Eisenberger, Andrew; Lentzsch, Suzanne

doi:10.1080/13506129.2019.1584892

Cited by 30 publications

(27 citation statements)

References 3 publications

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“…Despite promising preliminary results of NEOD001, a monoclonal antibody targeting misfolded amyloid proteins ( Gertz et al., 2016 ), and of miridesap, a monoclonal antibody targeting amyloid-bound SAP after pharmacological depletion of circulating SAP ( Richards et al., 2015 ; Richards et al., 2018 ), several clinical trials investigating these biologicals were recently interrupted due to futility analysis (for NEOD001, NCT02312206; NCT03168906) or to a change in benefit/risk profile (for miridesap, NCT03044353). A third chimeric fibril reactive monoclonal antibody, CAEL-101, formerly 11-1F4, is currently under clinical evaluation ( Edwards et al., 2019 ) (NCT02245867).…”

Section: Early Diagnosis Is Vitalmentioning

confidence: 99%

Treating Protein Misfolding Diseases: Therapeutic Successes Against Systemic Amyloidoses

Nevone

Merlini

2020

Front. Pharmacol.

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Misfolding and extracellular deposition of proteins is the hallmark of a heterogeneous group of conditions collectively termed protein misfolding and deposition diseases or amyloidoses. These include both localized (e.g. Alzheimer’s disease, prion diseases, type 2 diabetes mellitus) and systemic amyloidoses. Historically regarded as a group of maladies with limited, even inexistent, therapeutic options, some forms of systemic amyloidoses have recently witnessed a series of unparalleled therapeutic successes, positively impacting on their natural history and sometimes even on their incidence. In this review article we will revisit the most relevant of these accomplishments. Collectively, current evidence converges towards a crucial role of an early and conspicuous reduction or stabilization of the amyloid-forming protein in its native conformation. Such an approach can reduce disease incidence in at risk individuals, limit organ function deterioration, promote organ function recovery, improve quality of life and extend survival in diseased subjects. Therapeutic success achieved in these forms of systemic amyloidoses may guide the research on other protein misfolding and deposition diseases for which effective etiologic therapeutic options are still absent.

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Section: Early Diagnosis Is Vitalmentioning

confidence: 99%

Treating Protein Misfolding Diseases: Therapeutic Successes Against Systemic Amyloidoses

Nevone

Merlini

2020

Front. Pharmacol.

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“…Overall, organ response was demonstrated by 67% (12 of 18) of patients eligible for renal and/or cardiac response assessment and three patients with other organ involvement. The median time to response was three weeks (Edwards et al , ). Moreover, the mean Global Longitudinal Strain (GLS) improved significantly just after 12 weeks of treatment in 9 of 10 patients with cardiac involvement, but not in others.…”

Section: Monoclonal Antibodies Targetting Amyloid Fibrilsmentioning

confidence: 99%

Monoclonal antibodies in the treatment of AL amyloidosis: co‐targetting the plasma cell clone and amyloid deposits

Popková

Jelı́nek

2020

Br J Haematol

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Immunoglobulin light-chain amyloidosis (AL amyloidosis) is a rare disease in which a small plasma cell clone produces toxic misfolded proteins that deposit in organs and impair their function. Currently, the only available treatment approach is the elimination of clonal plasma cells. However, a rapid strike that halts and possibly reverses organ damage is crucial. The development of agents that facilitate the clearance of pathological fibrillar deposits, therefore reducing the frailty of patients, is the needed supplement to plasma celldirected therapy. Monoclonal antibodies provide therapy against malignant plasma cells (daratumumab, isatuximab, elotuzumab) but they are also able to target and eliminate the amyloid from organs (NEOD001, CAEL-101, dezamizumab). From the plasma cell-directed group, daratumumab in monotherapy has proved to be extremely efficient in relapsed AL amyloidosis, exceeding its results in multiple myeloma. Compared to other agents, monoclonal antibodies possess the advantage of high selectivity and low toxicity and could potentially become future game-changers in this field. Co-targetting of the plasma cell clone and amyloid deposits shall together be translated in the revolutionary improved outcome of potentially curable AL amyloidosis.

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“…Similarly, murine monoclonal antibody 11-1F4 targets the human light chain-related fibrils. It showed good efficacy with minimal toxicity in the phase 1 trial [ 22 ]. Further clinical trials on11-1F4 are currently being planned.…”

Section: Treatmentmentioning

confidence: 99%

AL amyloidosis: advances in diagnosis and management

Koh

2020

Blood Res

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Light chain (AL) amyloidosis is a disease in which malignant plasma cell clones affect multiple organs including the heart and kidney. The mechanism for organ function deterioration in AL amyloidosis differs from multiple myeloma. Thus, not all agents used to treat multiple myeloma shows similar efficacy in AL amyloidosis. In AL amyloidosis, both hematologic and organ responses after treatment are important to improve the clinical outcome. Especially, improving heart function is one of the key aspects in the treatment of AL amyloidosis. With recent advances in the understanding of the pathophysiologic mechanism of AL amyloidosis, novel treatment methods are under active trial. In this article, I have reviewed the advances in pathophysiology, diagnosis, risk stratification, and treatment of AL amyloidosis.

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One year follow up analysis of the phase 1a/b study of chimeric fibril-reactive monoclonal antibody 11-1F4 in patients with AL amyloidosis

Cited by 30 publications

References 3 publications

Treating Protein Misfolding Diseases: Therapeutic Successes Against Systemic Amyloidoses

Treating Protein Misfolding Diseases: Therapeutic Successes Against Systemic Amyloidoses

Monoclonal antibodies in the treatment of AL amyloidosis: co‐targetting the plasma cell clone and amyloid deposits

AL amyloidosis: advances in diagnosis and management

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