dezamizumab (GSK2398852) / GSK - LARVOL DELTA

A Rare Case of Gastric Amyloidosis in a Patient With End-Stage Renal Disease (ACG 2024) - "Management focuses on symptom alleviation and reducing amyloid load, with potential treatments including stem cell transplantation for AL amyloidosis. Treatment with the monoclonal antibody Dezamizumab is emerging, underscoring the necessity for a multidisciplinary approach to improve patient outcomes in GI amyloidosis."

Clinical • Amyloidosis • Anemia • Anorexia • Bone Marrow Transplantation • Chronic Kidney Disease • Constipation • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Nephrology • Renal Disease

An observational, non-interventional study for the follow-up of patients with amyloidosis who received miridesap followed by dezamizumab in a phase 1 study. (PubMed, Orphanet J Rare Dis) - P1 | "No further development of miridesap/dezamizumab is planned in amyloidosis. However, long-term follow-up of these patients may provide insight into whether active removal of amyloid deposits has an impact on disease progression."

Journal • Observational data • P1 data • Amyloidosis • Cardiovascular • APOA1

Pharmacodynamic evaluation and safety assessment of treatment with antibodies to serum amyloid P component in patients with cardiac amyloidosis: an open-label Phase 2 study and an adjunctive immuno-PET imaging study. (PubMed, BMC Cardiovasc Disord) - P1, P2 | "Unlike previous observations of visceral amyloid reduction, there was no appreciable evidence of amyloid removal in patients with cardiac amyloidosis in this Phase 2 trial, potentially related to limited cardiac uptake of dezamizumab as demonstrated in the immuno-PET study. The benefit-risk assessment for dezamizumab in cardiac amyloidosis was considered unfavourable after the incidence of large-vessel vasculitis and development for this indication was terminated. Trial registration NCT03044353 (2 February 2017) and NCT03417830 (25 January 2018)."

Journal • P2 data • PK/PD data • Amyloidosis • Cardiovascular • Vasculitis

Novel methods to determine complement activation in human serum induced by the complex of Dezamizumab and serum amyloid P. (PubMed, J Biol Chem) - "Both SAP and C1q binding, as determined by surface plasmon resonance and the two complement activation potency methods described here, reflect the mechanism of action of Dezamizumab. We conclude that these methods can be used to monitor Dezamizumab quality for drug release and stability testing, and the novel potency methods reported here can be potentially used to evaluate complement activity induced by other antigen-antibody complexes."

Journal • Amyloidosis

Monoclonal antibodies in the treatment of AL amyloidosis: co-targetting the plasma cell clone and amyloid deposits. (PubMed, Br J Haematol) - "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). 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."

Journal • Review

The Pentraxins 1975-2018: Serendipity, Diagnostics and Drugs. (PubMed, Front Immunol) - "Meanwhile, the obligate therapeutic partnership of miridesap, to deplete circulating SAP, and dezamizumab, a humanized monoclonal anti-SAP antibody that targets residual SAP in amyloid deposits, produces unprecedented removal of amyloid from the tissues and improves organ function. The present personal and critical perspective on the pentraxins reports, for the first time, the key role of serendipity in our work since 1975. (345 words)."

Journal

Multiple Treatment Session Study to Assess GSK2398852 Administered Following and Along With GSK2315698 (clinicaltrials.gov) - P2; N=7; Terminated; Sponsor: GlaxoSmithKline; N=30 ➔ 7; Trial completion date: Sep 2021 ➔ Jan 2019; Suspended ➔ Terminated; Trial primary completion date: Sep 2021 ➔ Jan 2019; Change in benefit/risk profile

Clinical • Enrollment change • Trial completion date • Trial primary completion date • Trial termination