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Drugs Sep 2023Rozanolixizumab (rozanolixizumab-noli; RYSTIGGO) is a high affinity humanized immunoglobulin G4 monoclonal antibody directed against human neonatal Fc receptor (FcRn).... (Review)
Review
Rozanolixizumab (rozanolixizumab-noli; RYSTIGGO) is a high affinity humanized immunoglobulin G4 monoclonal antibody directed against human neonatal Fc receptor (FcRn). Administered subcutaneously, it is being developed by UCB Pharma for the treatment of autoimmune diseases and received its first approval on 27 June 2023 in the USA for the treatment of generalized myasthenia gravis (gMG) in adults who are anti-acetylcholine receptor (AChR) or anti-muscle-specific kinase (MuSK) antibody positive. Rozanolixizumab is the first agent to be approved in the USA for both anti-AChR and anti-MuSK antibody-positive gMG. A regulatory assessment of rozanolixizumab for the treatment of gMG is currently underway in the EU and Japan. Clinical development is ongoing for the treatment of leucine-rich glioma-inactivated 1 autoimmune encephalitis, myelin oligodendrocyte glycoprotein (MOG) antibody disease and severe fibromyalgia syndrome. This article summarizes the milestones in the development of rozanolixizumab leading to this first approval for the treatment of gMG in adults who are anti-AChR or anti-MuSK antibody positive.
Topics: Adult; Infant, Newborn; Humans; Antibodies, Monoclonal, Humanized; Encephalitis; Glioma; Myasthenia Gravis
PubMed: 37656420
DOI: 10.1007/s40265-023-01933-1 -
Annual Review of Medicine Jan 2024Multiple myeloma is a cancer of bone marrow plasma cells that represents approximately 10% of hematologic malignancies. Though it is typically incurable, a remarkable... (Review)
Review
Multiple myeloma is a cancer of bone marrow plasma cells that represents approximately 10% of hematologic malignancies. Though it is typically incurable, a remarkable suite of new therapies developed over the last 25 years has enabled durable disease control in most patients. This article briefly introduces the clinical features of multiple myeloma and aspects of multiple myeloma biology that modern therapies exploit. Key current and emerging treatment modalities are then reviewed, including cereblon-modulating agents, proteasome inhibitors, monoclonal antibodies, other molecularly targeted therapies (selinexor, venetoclax), chimeric antigen receptor T cells, T cell-engaging bispecific antibodies, and antibody-drug conjugates. For each modality, mechanism of action and clinical considerations are discussed. These therapies are combined and sequenced in modern treatment pathways, discussed at the conclusion of the article, which have led to substantial improvements in outcomes for multiple myeloma patients in recent years.
Topics: Humans; Multiple Myeloma; Immunotherapy; Proteasome Inhibitors; Antibodies, Monoclonal; Biological Therapy
PubMed: 37729027
DOI: 10.1146/annurev-med-050522-033815 -
International Journal of Molecular... Sep 2023In an ever-increasing aged world, Alzheimer's disease (AD) represents the first cause of dementia and one of the first chronic diseases in elderly people. With 55... (Review)
Review
In an ever-increasing aged world, Alzheimer's disease (AD) represents the first cause of dementia and one of the first chronic diseases in elderly people. With 55 million people affected, the WHO considers AD to be a disease with public priority. Unfortunately, there are no final cures for this pathology. Treatment strategies are aimed to mitigate symptoms, i.e., acetylcholinesterase inhibitors (AChEI) and the N-Methyl-D-aspartate (NMDA) antagonist Memantine. At present, the best approaches for managing the disease seem to combine pharmacological and non-pharmacological therapies to stimulate cognitive reserve. Over the last twenty years, a number of drugs have been discovered acting on the well-established biological hallmarks of AD, deposition of β-amyloid aggregates and accumulation of hyperphosphorylated tau protein in cells. Although previous efforts disappointed expectations, a new era in treating AD has been working its way recently. The Food and Drug Administration (FDA) gave conditional approval of the first disease-modifying therapy (DMT) for the treatment of AD, aducanumab, a monoclonal antibody (mAb) designed against Aβ plaques and oligomers in 2021, and in January 2023, the FDA granted accelerated approval for a second monoclonal antibody, Lecanemab. This review describes ongoing clinical trials with DMTs and non-pharmacological therapies. We will also present a future scenario based on new biomarkers that can detect AD in preclinical or prodromal stages, identify people at risk of developing AD, and allow an early and curative treatment.
Topics: United States; Humans; Aged; Alzheimer Disease; Acetylcholinesterase; Amyloid beta-Peptides; Memantine; Antibodies, Monoclonal
PubMed: 37762203
DOI: 10.3390/ijms241813900 -
Journal of Translational Medicine Sep 2023Osteoporosis is a systemic bone disease characterized by low bone mass, microarchitectural deterioration, increased bone fragility, and fracture susceptibility. It... (Review)
Review
Osteoporosis is a systemic bone disease characterized by low bone mass, microarchitectural deterioration, increased bone fragility, and fracture susceptibility. It commonly occurs in older people, especially postmenopausal women. As global ageing increases, osteoporosis has become a global burden. There are a number of medications available for the treatment of osteoporosis, categorized as anabolic and anti-resorptive. Unfortunately, there is no drugs which have dual influence on bone, while all drugs have limitations and adverse events. Some serious adverse events include jaw osteonecrosis and atypical femoral fracture. Recently, a novel medication has appeared that challenges this pattern. Romosozumab is a novel drug monoclonal antibody to sclerostin encoded by the SOST gene. It has been used in Japan since 2019 and has achieved promising results in treating osteoporosis. However, it is also accompanied by some controversy. While it promotes rapid bone growth, it may cause serious adverse events such as cardiovascular diseases. There has been scepticism about the drug since its inception. Therefore, the present review comprehensively covered romosozumab from its inception to its clinical application, from animal studies to human studies, and from safety to cost. We hope to provide a better understanding of romosozumab for its clinical application.
Topics: Animals; Female; Humans; Aged; Osteoporosis; Antibodies, Monoclonal; Aging; Bone Development
PubMed: 37759285
DOI: 10.1186/s12967-023-04563-z -
Bioconjugate Chemistry Nov 2023Antibody-drug conjugates (ADCs) are targeted immunoconjugate constructs that integrate the potency of cytotoxic drugs with the selectivity of monoclonal antibodies,... (Review)
Review
Antibody-drug conjugates (ADCs) are targeted immunoconjugate constructs that integrate the potency of cytotoxic drugs with the selectivity of monoclonal antibodies, minimizing damage to healthy cells and reducing systemic toxicity. Their design allows for higher doses of the cytotoxic drug to be administered, potentially increasing efficacy. They are currently among the most promising drug classes in oncology, with efforts to expand their application for nononcological indications and in combination therapies. Here we provide a detailed overview of the recent advances in ADC research and consider future directions and challenges in promoting this promising platform to widespread therapeutic use. We examine data from the CAS Content Collection, the largest human-curated collection of published scientific information, and analyze the publication landscape of recent research to reveal the exploration trends in published documents and to provide insights into the scientific advances in the area. We also discuss the evolution of the key concepts in the field, the major technologies, and their development pipelines with company research focuses, disease targets, development stages, and publication and investment trends. A comprehensive concept map has been created based on the documents in the CAS Content Collection. We hope that this report can serve as a useful resource for understanding the current state of knowledge in the field of ADCs and the remaining challenges to fulfill their potential.
Topics: Humans; Immunoconjugates; Antineoplastic Agents; Antibodies, Monoclonal; Neoplasms
PubMed: 37821099
DOI: 10.1021/acs.bioconjchem.3c00374 -
The Journal of Experimental Medicine Jul 2023The field of asthma has undergone a dramatic change in recent years. Advances in our understanding of type 2 airway inflammation have driven the discovery of monoclonal... (Review)
Review
The field of asthma has undergone a dramatic change in recent years. Advances in our understanding of type 2 airway inflammation have driven the discovery of monoclonal antibodies targeting specific aspects of the immune pathway. In landmark trials, these drugs have shown efficacy in reducing asthma attacks and exposure to oral corticosteroids, important causes of morbidity in people with asthma. Our review explores the key features of type 2 inflammation in asthma and summarizes the clinical trial evidence of the novel monoclonal antibody treatments and future avenues for treatment.
Topics: Humans; Asthma; Antibodies, Monoclonal; Inflammation; Biological Therapy
PubMed: 37265457
DOI: 10.1084/jem.20221212 -
Annals of Family Medicine 2024We conducted a meta-analysis to evaluate clinically meaningful benefits and harms of monoclonal antibodies targeting amyloid in patients with Alzheimer dementia. (Meta-Analysis)
Meta-Analysis Review
PURPOSE
We conducted a meta-analysis to evaluate clinically meaningful benefits and harms of monoclonal antibodies targeting amyloid in patients with Alzheimer dementia.
METHODS
We searched PubMed, Cochrane CENTRAL, and 5 trial registries, as well as the reference lists of identified studies. We included randomized controlled trials comparing a monoclonal antibody with placebo at a dose consistent with that used in phase 3 trials or for Food and Drug Administration approval. Studies had to report at least 1 clinically relevant benefit or harm. Data were extracted independently by at least 2 researchers for random effects meta-analysis. Changes in cognitive and functional scales were compared between groups, and each difference was assessed to determine if it met the minimal clinically important difference (MCID).
RESULTS
We identified 19 publications with 23,202 total participants that evaluated 8 anti-amyloid antibodies. There were small improvements over placebo in the Alzheimer's Disease Assessment Scale (ADAS)-Cog-11 to -14 score (standardized mean difference = -0.07; 95% CI, -0.10 to -0.04), Mini Mental State Examination score (0.32 points; 95% CI, 0.13 to 0.50), and Clinical Dementia Rating-Sum of Boxes scale score (mean difference =-0.18 points; 95% CI, -0.34 to -0.03), and the combined functional scores (standardized mean difference = 0.09; 95% CI, 0.05 to 0.13). None of the changes, including those for lecanemab, aducanumab, and donanemab, exceeded the MCID. Harms included significantly increased risks of amyloid-related imaging abnormalities (ARIA)-edema (relative risk [RR] = 10.29; number needed to harm [NNH] = 9), ARIA-hemorrhage (RR = 1.74; NNH = 13), and symptomatic ARIA-edema (RR = 24.3; NNH = 86).
CONCLUSIONS
Although monoclonal antibodies targeting amyloid provide small benefits on cognitive and functional scales in patients with Alzheimer dementia, these improvements are far below the MCID for each outcome and are accompanied by clinically meaningful harms.
Topics: United States; Humans; Alzheimer Disease; Antibodies, Monoclonal; Mental Status and Dementia Tests; Edema; Antibodies, Monoclonal, Humanized
PubMed: 38253509
DOI: 10.1370/afm.3050 -
Frontiers in Immunology 2023Inotuzumab ozogamicin (InO) is an antibody drug conjugate composed of a humanized monoclonal antibody targeting the cell surface receptor CD22 coupled to a cytotoxic... (Review)
Review
Inotuzumab ozogamicin (InO) is an antibody drug conjugate composed of a humanized monoclonal antibody targeting the cell surface receptor CD22 coupled to a cytotoxic calicheamicin payload an acid labile linker. InO has shown significant activity in relapsed and refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL) in both single agent and combination chemotherapy regimens in adult and pediatric trials. Its use in newly diagnosed elderly patients has also been established while clinical trials investigating its use in newly diagnosed pediatric patients and fit adults are ongoing. Notable toxicities include sinusoidal obstruction syndrome (SOS), particularly in patients who undergo hematopoietic stem cell transplantation (HSCT) after InO as well as myelosuppression and B-cell aplasia which confer increased infection risk, particularly in combination with cytotoxic chemotherapy. In the relapsed/refractory (R/R) setting, the planned subsequent curative therapy modality must be considered when using InO to mitigate SOS risk if proceeding to HSCT and account for potential B-cell aplasia if proceeding to chimeric antigen receptor CAR-T therapy. Studies exploring mechanisms of resistance or failure of InO are ongoing but modulation or loss CD22 expression, alternative CD22 splicing, and high Bcl-2 expression have been implicated. In this review, we will summarize the currently available data on InO, with an emphasis on pediatric trials, and explore future directions including combinatorial therapy.
Topics: Adult; Aged; Humans; Child; Inotuzumab Ozogamicin; Burkitt Lymphoma; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; Antibodies, Monoclonal, Humanized; Precursor Cell Lymphoblastic Leukemia-Lymphoma
PubMed: 37600823
DOI: 10.3389/fimmu.2023.1237738 -
Molecules (Basel, Switzerland) Sep 2023Antibody engineering has developed into a wide-reaching field, impacting a multitude of industries, most notably healthcare and diagnostics. The seminal work on... (Review)
Review
Antibody engineering has developed into a wide-reaching field, impacting a multitude of industries, most notably healthcare and diagnostics. The seminal work on developing the first monoclonal antibody four decades ago has witnessed exponential growth in the last 10-15 years, where regulators have approved monoclonal antibodies as therapeutics and for several diagnostic applications, including the remarkable attention it garnered during the pandemic. In recent years, antibodies have become the fastest-growing class of biological drugs approved for the treatment of a wide range of diseases, from cancer to autoimmune conditions. This review discusses the field of therapeutic antibodies as it stands today. It summarizes and outlines the clinical relevance and application of therapeutic antibodies in treating a landscape of diseases in different disciplines of medicine. It discusses the nomenclature, various approaches to antibody therapies, and the evolution of antibody therapeutics. It also discusses the risk profile and adverse immune reactions associated with the antibodies and sheds light on future applications and perspectives in antibody drug discovery.
Topics: Humans; Medicine; Antibodies, Monoclonal; Autoimmune Diseases; Biological Products; Clinical Relevance
PubMed: 37764213
DOI: 10.3390/molecules28186438 -
European Review For Medical and... Oct 2023This paper aims to review biologics in allergic rhinitis (AR). Biologic agents of Omalizumab, Dupilumab, Mepolizumab, Reslizumab, and Benralizumab are reviewed in... (Review)
Review
This paper aims to review biologics in allergic rhinitis (AR). Biologic agents of Omalizumab, Dupilumab, Mepolizumab, Reslizumab, and Benralizumab are reviewed in detail. The search is performed in "Pubmed," "Google," Google Scholar" and EBSCO Academic Search Ultimate (EKUAL) database of Kırıkkale University Library from 2021 to 2000, and randomized and/or placebo-controlled studies, review papers, meta-analysis, and reports are taken into consideration. The search was performed with the keywords of "allergic rhinitis," "biologics," "biologic agents," "Omalizumab," "Dupilumab," "Mepolizumab," "Reslizumab," "Benralizumab," "Anti IgE," "Anti-IL-4/IL-13", "Anti IL-5". Search is also performed in the "U.S. Food and Drug Administration" (FDA) and "European Medicines Agency" (EMA) web systems. Biological agents such as monoclonal antibodies (MAb) in treatment are called biological therapy or biotherapy. Omalizumab is a humanized Anti-IgE monoclonal antibody. Omalizumab treatment improved the Daily Nasal Rescue Medication Score (DNSSS) and decreased the use of antiallergic drugs in seasonal and perennial AR and rhino-conjunctivitis. Omalizumab is also used in specific immunotherapy patients with allergic rhinitis and reduced allergic reactions associated with allergen immunotherapy, such as anaphylaxis. Dupilumab is an Anti-IL-4/IL-13 biologic agent. Dupilumab treatment significantly improved sino-nasal Outcome Test (SNOT-22) total scores in perennial allergic rhinitis. Anti-IL-5 monoclonal antibodies of Mepolizumab, Reslizumab Benralizumab reduce the number of eosinophils in the blood and tissue, corticosteroid addiction and asthma attacks are reduced, and their use in the treatment of severe eosinophilic asthma has been approved. Biologics, especially Omalizumab, and Dupilumab, may be used more in allergic rhinitis.
Topics: Humans; Anti-Asthmatic Agents; Antibodies, Monoclonal; Asthma; Biological Products; Interleukin-13; Omalizumab; Rhinitis, Allergic
PubMed: 37869947
DOI: 10.26355/eurrev_202310_34069