A Clinical Prediction Model to Determine Probability of Response to Certolizumab Pegol for Crohn ’s Disease
ConclusionsPatients who are predicted to have accelerated baseline CZP clearance are at risk of subtherapeutic CZP concentrations. Patient-level probabilities for a composite remission outcome can be predicted for patients with CD by entering commonly available patient- and disease-related factors into an online CDST (https://premedibd.com) incorporating predicted CZP clearance. (Source: BioDrugs)
Source: BioDrugs - December 24, 2021 Category: Drugs & Pharmacology Source Type: research

Patients Retransitioning from Biosimilar TNF α Inhibitor to the Corresponding Originator After Initial Transitioning to the Biosimilar: A Systematic Review
ConclusionsIn studies on transitioning patients from TNF α originator to biosimilar, 8% of patients retransitioned. Retransitioning appeared to be lower in studies that included only patients with stable disease and in studies that did not offer patients the option of retransitioning at the introduction of the biosimilar. In addition, retransitioning app eared to be lower in studies that implemented extra laboratory monitoring as part of the biosimilar implementation strategy. Clinicians should consider implementing these suggestions as they might reduce retransitioning rates and improve the introduction of biosimila...
Source: BioDrugs - December 6, 2021 Category: Drugs & Pharmacology Source Type: research

SARS-CoV-2 Neutralization in Convalescent Plasma and Commercial Lots of Plasma-Derived Immunoglobulin
ConclusionsSARS-CoV-2 reactivity and neutralization capacity in IVIG/SCIG produced from US plasma rapidly and in part exponentially increased in the first half of 2021. The observed increase of final container potencies is likely trailing the serological status of the US donor population in terms of COVID-19 convalescence and vaccination by at least 5 months due to production lead times and should in principle continue at least until Fall 2021. In summary, the data support rapidly increasing levels of anti-SARS-CoV-2 antibodies in IVIG/SCIG products, implicating that a certain level of protection could be possible against ...
Source: BioDrugs - November 29, 2021 Category: Drugs & Pharmacology Source Type: research

Evolving Perceptions, Utilization, and Real-World Implementation Experiences of Oncology Monoclonal Antibody Biosimilars in the USA: Perspectives from Both Payers and Physicians
ConclusionsUS payers and physicians who have experience with biosimilars have favorable views of oncology biosimilars, particularly for treatment-na ïve patients. A framework for integrating biosimilars into oncology practice is developing, primarily driven by insurance coverage, contracting, and cost benefits. (Source: BioDrugs)
Source: BioDrugs - November 25, 2021 Category: Drugs & Pharmacology Source Type: research

Switching from Biologic to Biosimilar Products: Insight from an Integrated Health Care System
AbstractBiologics are indicated for the treatment of a wide range of conditions and have transformed care in several therapeutic areas; however, they are expensive for both health care systems and patients. The use of biosimilars, which are approved by the US  Food and Drug Administration as being “highly similar” to the originator biologic, has the potential to change the health care landscape in the biologic space through considerable cost savings for both payors and patients. With the introduction of biosimilars, organizations are increasingly ev aluating how to switch patients from originator biologics...
Source: BioDrugs - November 24, 2021 Category: Drugs & Pharmacology Source Type: research

Nerve Growth Factor (NGF) Inhibitors and Related Agents for Chronic Musculoskeletal Pain: A Comprehensive Review
AbstractMusculoskeletal pain such as osteoarthritis (OA) and low back pain (LBP) are very common and contribute to enormous burden and societal costs, despite dramatic therapeutic advances over recent decades. Novel approaches and targeted therapies are required to satisfy the urgent unmet medical need of musculoskeletal pain relief  in both conditions. Nerve growth factor (NGF) inhibitors have utilized novel mechanisms different from conventional drugs, which have a variety of gastrointestinal, cardiac, or renal adverse effects. Several phase 2/3 studies have been accomplished for these drugs, such as tanezumab, fasi...
Source: BioDrugs - November 22, 2021 Category: Drugs & Pharmacology Source Type: research

Anti-Drug Antibody Formation Against Biologic Agents in Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis
ConclusionsDifferences in analytical methods to detect ADA hamper comparison of true ADA rates across biologics in IBD. Use of combination therapy with immunomodulators appeared to reduce ADA positivity for most biologics. For infliximab, ADA were associated with reduced drug efficacy and increased adverse events. (Source: BioDrugs)
Source: BioDrugs - November 19, 2021 Category: Drugs & Pharmacology Source Type: research

Targeted Therapy for Primary Sj ögren’s Syndrome: Where are We Now?
AbstractPrimary Sj ögren's syndrome (pSS) is an autoimmune exocrinopathy characterized by dryness symptoms. This review briefly describes recent advances in the targeted therapies for pSS. Biologics evaluated for pSS treatment mainly include B cell-depleting agents, inhibitors of B cell activation, and agents that ta rget co-signaling molecules or proinflammatory cytokines. Small molecule inhibitors that target signaling pathways have also been evaluated. However, current evidence for the efficacy of targeted therapies in pSS is still sparse. Although ianalumab (an anti–B cell-activating factor [BAFF]-receptor a...
Source: BioDrugs - November 3, 2021 Category: Drugs & Pharmacology Source Type: research

Critical Analysis of cGMP Large-Scale Expansion Process in Bioreactors of Human Induced Pluripotent Stem Cells in the Framework of Quality by Design
AbstractHuman induced pluripotent stem cells (hiPSCs) are manufactured as advanced therapy medicinal products for tissue replacement applications. With this aim, the feasibility of hiPSC large-scale expansion in existing bioreactor systems under current good manufacturing practices (cGMP) has been tested. Yet, these attempts have lacked a paradigm shift in culture settings and technologies tailored to hiPSCs, which jeopardizes their clinical translation. The best approach for industrial scale-up of high-quality hiPSCs is to design their manufacturing process by following quality-by-design (QbD) principles: a scientific, ri...
Source: BioDrugs - November 2, 2021 Category: Drugs & Pharmacology Source Type: research

Acknowledgement to Referees
(Source: BioDrugs)
Source: BioDrugs - November 2, 2021 Category: Drugs & Pharmacology Source Type: research

Critical Analysis of cGMP Large-Scale Expansion Process in Bioreactors of Human Induced Pluripotent Stem Cells in the Framework of Quality by Design
AbstractHuman induced pluripotent stem cells (hiPSCs) are manufactured as advanced therapy medicinal products for tissue replacement applications. With this aim, the feasibility of hiPSC large-scale expansion in existing bioreactor systems under current good manufacturing practices (cGMP) has been tested. Yet, these attempts have lacked a paradigm shift in culture settings and technologies tailored to hiPSCs, which jeopardizes their clinical translation. The best approach for industrial scale-up of high-quality hiPSCs is to design their manufacturing process by following quality-by-design (QbD) principles: a scientific, ri...
Source: BioDrugs - November 2, 2021 Category: Drugs & Pharmacology Source Type: research

Acknowledgement to Referees
(Source: BioDrugs)
Source: BioDrugs - November 2, 2021 Category: Drugs & Pharmacology Source Type: research

Anti-Drug Antibody Formation Against Biologic Agents in Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis
ConclusionsDifferences in analytical methods to detect ADA hamper comparison of true ADA rates across biologics in IBD. Use of combination therapy with immunomodulators appeared to reduce ADA positivity for most biologics. For infliximab, ADA were associated with reduced drug efficacy and increased adverse events. (Source: BioDrugs)
Source: BioDrugs - November 1, 2021 Category: Drugs & Pharmacology Source Type: research

Nerve Growth Factor (NGF) Inhibitors and Related Agents for Chronic Musculoskeletal Pain: A Comprehensive Review
AbstractMusculoskeletal pain such as osteoarthritis (OA) and low back pain (LBP) are very common and contribute to enormous burden and societal costs, despite dramatic therapeutic advances over recent decades. Novel approaches and targeted therapies are required to satisfy the urgent unmet medical need of musculoskeletal pain relief  in both conditions. Nerve growth factor (NGF) inhibitors have utilized novel mechanisms different from conventional drugs, which have a variety of gastrointestinal, cardiac, or renal adverse effects. Several phase 2/3 studies have been accomplished for these drugs, such as tanezumab, fasi...
Source: BioDrugs - November 1, 2021 Category: Drugs & Pharmacology Source Type: research

Targeting the Inside of Cells with Biologicals: Chemicals as a Delivery Strategy
AbstractDelivering macromolecules into the cytosol or nucleus is possible in vitro for DNA, RNA and proteins, but translation for clinical use has been limited. Therapeutic delivery of macromolecules into cells requires overcoming substantially higher barriers compared to the use of small molecule drugs or proteins in the extracellular space. Breakthroughs like DNA delivery for approved gene therapies and RNA delivery for silencing of genes (patisiran, ONPATTRO®, Alnylam Pharmaceuticals, Cambridge, MA, USA) or for vaccination such as the RNA-based coronavirus disease 2019 (COVID-19) vaccines demonstrated the feasibilit...
Source: BioDrugs - October 27, 2021 Category: Drugs & Pharmacology Source Type: research

Incidence of and Reasons and Determinants Associated with Retransitioning from Biosimilar Etanercept to Originator Etanercept
ConclusionWhen introducing a biosimilar in clinical care, clinicians should anticipate that one in seven patients will retransition to the originator. A (perceived) loss of effect was the most frequently reported reason for retransitioning. Patients who visited the rheumatology department more frequently had an increased risk of retransitioning, which is likely to be related to patients reporting a loss of effect and to adverse events resulting in more visits to the rheumatology department. (Source: BioDrugs)
Source: BioDrugs - October 26, 2021 Category: Drugs & Pharmacology Source Type: research

Efficacy, Safety and Immunogenicity of AVT02 Versus Originator Adalimumab in Subjects with Moderate to Severe Chronic Plaque Psoriasis: A Multicentre, Double-Blind, Randomised, Parallel Group, Active Control, Phase III Study
ConclusionObjective and subjective measures of efficacy supported the evaluation of biosimilarity between AVT02 and originator adalimumab at Week 16 and until Week 50, in switched and continued treatment groups. AVT02 was safe and well tolerated, with a safety and immunogenicity profile similar to that observed in originator adalimumab with no clinically meaningful difference between the two.Clinical Trial RegistrationEudraCT: 2017-003367-35; ClinicalTrials.gov: NCT03849404. (Source: BioDrugs)
Source: BioDrugs - October 16, 2021 Category: Drugs & Pharmacology Source Type: research

Anti-VEGF and Other Novel Therapies for Neovascular Age-Related Macular Degeneration: An Update
AbstractAge-related macular degeneration (AMD) is a leading cause of visual impairment and blindness in older adults. The prognosis for the neovascular type of advanced AMD improved with the introduction of biological drugs with antiangiogenic properties, beginning with off-label bevacizumab, which was first used intravitreally in 2006. These drugs target newly formed vessels that grow beneath the center of the retina, causing loss of central vision, and they can help to maintain or improve vision. Repeated intravitreal injections are needed to achieve prolonged inhibition of proangiogenic cytokines, primarily vascular end...
Source: BioDrugs - October 16, 2021 Category: Drugs & Pharmacology Source Type: research

Efficacy, Safety and Immunogenicity of AVT02 Versus Originator Adalimumab in Subjects with Moderate to Severe Chronic Plaque Psoriasis: A Multicentre, Double-Blind, Randomised, Parallel Group, Active Control, Phase III Study
ConclusionObjective and subjective measures of efficacy supported the evaluation of biosimilarity between AVT02 and originator adalimumab at Week 16 and until Week 50, in switched and continued treatment groups. AVT02 was safe and well tolerated, with a safety and immunogenicity profile similar to that observed in originator adalimumab with no clinically meaningful difference between the two.Clinical Trial RegistrationEudraCT: 2017-003367-35; ClinicalTrials.gov: NCT03849404. (Source: BioDrugs)
Source: BioDrugs - October 16, 2021 Category: Drugs & Pharmacology Source Type: research

Anti-VEGF and Other Novel Therapies for Neovascular Age-Related Macular Degeneration: An Update
AbstractAge-related macular degeneration (AMD) is a leading cause of visual impairment and blindness in older adults. The prognosis for the neovascular type of advanced AMD improved with the introduction of biological drugs with antiangiogenic properties, beginning with off-label bevacizumab, which was first used intravitreally in 2006. These drugs target newly formed vessels that grow beneath the center of the retina, causing loss of central vision, and they can help to maintain or improve vision. Repeated intravitreal injections are needed to achieve prolonged inhibition of proangiogenic cytokines, primarily vascular end...
Source: BioDrugs - October 16, 2021 Category: Drugs & Pharmacology Source Type: research

Large-Scale Postmarketing Surveillance of Biological Drugs for Immune-Mediated Inflammatory Diseases Through an Italian Distributed Multi-Database Healthcare Network: The VALORE Project
ConclusionThe VALORE project multi-database network has access to data on more than 140,000 biological drug users (and> 0.5 million PYs) from 13 Italian regions during the years 2010 –2019, which will be further expanded with the inclusion of data from other regions and more recent calendar years. Overall, the cumulated amount of person-time of exposure to biological drugs approved for IMIDs provides enough statistical power to investigate weak/moderate associations of almost all individual compounds and the most relevant safety outcomes. Moreover, this network may offer the opportunity to investigate the intercha...
Source: BioDrugs - October 12, 2021 Category: Drugs & Pharmacology Source Type: research

Targeting Leukocyte Trafficking in Inflammatory Bowel Disease
AbstractIn the last two decades, understanding of inflammatory bowel disease (IBD) immunopathogenesis has expanded considerably. Histopathological examination of the intestinal mucosa in IBD demonstrates the presence of a chronic inflammatory cell infiltrate. Research has focused on identifying mechanisms of immune cell trafficking to the gastrointestinal tract that may represent effective gut-selective targets for IBD therapy whilst avoiding systemic immunosuppression that may be associated with off-target adverse effects such as infection and malignancy. Integrins are cell surface receptors that can bind to cellular adhe...
Source: BioDrugs - October 6, 2021 Category: Drugs & Pharmacology Source Type: research

Vaccine-Associated Enhanced Viral Disease: Implications for Viral Vaccine Development
AbstractVaccine-associated enhanced disease (VAED) is a serious barrier to attaining successful virus vaccines in human and veterinary medicine. VAED occurs as two different immunopathologies, antibody-dependent enhancement (ADE) and vaccine-associated hypersensitivity (VAH). ADE contributes to the pathology of disease caused by four dengue viruses (DENV) through control of the intensity of cellular infection. Products of virus-infected cells are toxic. A partially protective yellow fever chimeric tetravalent DENV vaccine sensitized seronegative children to ADE breakthrough infections. A live-attenuated tetravalent whole v...
Source: BioDrugs - September 9, 2021 Category: Drugs & Pharmacology Source Type: research

Comparative Risk of Arterial Thromboembolic Events Between Aflibercept and Ranibizumab in Patients with Maculopathy: A Population-Based Retrospective Cohort Study
ConclusionThe use of aflibercept in patients with maculopathy was associated with a lower risk of ATE than was the use of ranibizumab. There was no difference in mortality risk between the two groups. Our study could provide strong grounds for future prospective studies to confirm the findings. (Source: BioDrugs)
Source: BioDrugs - September 8, 2021 Category: Drugs & Pharmacology Source Type: research

Cryopreservation of NK and T Cells Without DMSO for Adoptive Cell-Based Immunotherapy
AbstractDimethylsufoxide (DMSO) being universally used as a cryoprotectant in clinical adoptive cell-therapy settings to treat hematological malignancies and solid tumors is a growing concern, largely due to its broad toxicities. Its use has been associated with significant clinical side effects —cardiovascular, neurological, gastrointestinal, and allergic—in patients receiving infusions of cell-therapy products. DMSO has also been associated with altered expression of natural killer (NK) and T-cell markers and their in vivo function, not to mention difficulties in scaling up DMSO-based cryoprotectants, which i...
Source: BioDrugs - August 24, 2021 Category: Drugs & Pharmacology Source Type: research

Is There Any Research Evidence Beyond Surveys and Opinion Polls on Automatic Substitution of Biological Medicines? A Systematic Review
ConclusionsThe current research evidence on the automatic substitution of biologics is scarce and of low to moderate quality, reflecting low stakeholder knowledge and their cautious attitude towards biosimilars. The safe and efficient implementation of automatic substitution requires well-designed practices, pilot studies, and evolving legislation. (Source: BioDrugs)
Source: BioDrugs - August 16, 2021 Category: Drugs & Pharmacology Source Type: research

Analytical Similarity Assessment of ABP 959 in Comparison with Eculizumab Reference Product
ConclusionsBased on these results, it can be concluded that ABP  959 is analytically similar to eculizumab RP. (Source: BioDrugs)
Source: BioDrugs - July 22, 2021 Category: Drugs & Pharmacology Source Type: research

Advances in Immunotherapy for Diffuse Large B Cell Lymphoma
AbstractDiffuse large B cell lymphoma (DLBCL) is a heterogeneous disease that is normally treated with combination chemotherapy combined with the anti-CD20 monoclonal antibody rituximab. Although about two-thirds of patients are cured with initial chemo-immunotherapy, a sizable minority of patients will have relapsed or refractory (r/r) DLBCL. Standard therapy for r/r DLBCL is salvage chemotherapy followed by autologous stem cell transplantation (ASCT); however, a minority of patients have long-term remission with this approach. In recent years, there has been a proliferation of immunotherapies for the treatment of DLBCL t...
Source: BioDrugs - July 15, 2021 Category: Drugs & Pharmacology Source Type: research

Efficacy and Safety of Bevacizumab Biosimilar FKB238 Versus Originator Bevacizumab: Results from AVANA, a Phase III Trial in Patients with Non-Squamous Non-Small-Cell Lung Cancer (non-sq-NSCLC)
ConclusionsEfficacy equivalence was demonstrated between the two drugs, and safety profiles were similar. There were no meaningful differences in efficacy and safety between FKB238 or bevacizumab in patients with non-sq-NSCLC.Trial registration numberNCT02810457. (Source: BioDrugs)
Source: BioDrugs - July 15, 2021 Category: Drugs & Pharmacology Source Type: research

Novel Targeted Biological Agents for the Treatment of Atopic Dermatitis
AbstractAtopic dermatitis (AD) is a common inflammatory dermatologic disease clinically characterized by intense itch, recurrent eczematous lesions, and a chronic or relapsing disease course. Mild-to-moderate AD can be controlled by using moisturizers and topical immunomodulators such as topical corticosteroids and calcineurin inhibitors. If topical therapies fail, phototherapy and systemic immunosuppressant therapies, such as ciclosporin, methotrexate, and azathioprine, can be considered. However, relapse and side effects could still occur. The pathogenesis of AD involves epidermal barrier dysfunction, skin microbiome abn...
Source: BioDrugs - July 2, 2021 Category: Drugs & Pharmacology Source Type: research

Efficacy and Safety of Bevacizumab Biosimilar FKB238 Versus Originator Bevacizumab: Results from AVANA, a Phase III Trial in Patients with Non-Squamous Non-Small-Cell Lung Cancer (non-sq-NSCLC)
ConclusionsEfficacy equivalence was demonstrated between the two drugs, and safety profiles were similar. There were no meaningful differences in efficacy and safety between FKB238 or bevacizumab in patients with non-sq-NSCLC.Trial registration numberNCT02810457. (Source: BioDrugs)
Source: BioDrugs - July 1, 2021 Category: Drugs & Pharmacology Source Type: research

Restoring Protein Expression in Neuromuscular Conditions: A Review Assessing the Current State of Exon Skipping/Inclusion and Gene Therapies for Duchenne Muscular Dystrophy and Spinal Muscular Atrophy
AbstractThe debilitating neuromuscular disorders Duchenne muscular dystrophy (DMD) and spinal muscular atrophy (SMA), which harm 1 in 5000 newborn males and 1 in 11,000 newborns, respectively, are marked by progressive muscle wasting among other complications. While DMD causes generalized muscle weakness due to the absence of the dystrophin protein, SMA patients generally face motor neuron degeneration because of the lack of the survival motor neuron (SMN) protein. Many of the most promising therapies for both conditions restore the absent proteins dystrophin and SMN. Antisense oligonucleotide-mediated exon skipping and in...
Source: BioDrugs - July 1, 2021 Category: Drugs & Pharmacology Source Type: research

Novel Targeted Biological Agents for the Treatment of Atopic Dermatitis
AbstractAtopic dermatitis (AD) is a common inflammatory dermatologic disease clinically characterized by intense itch, recurrent eczematous lesions, and a chronic or relapsing disease course. Mild-to-moderate AD can be controlled by using moisturizers and topical immunomodulators such as topical corticosteroids and calcineurin inhibitors. If topical therapies fail, phototherapy and systemic immunosuppressant therapies, such as ciclosporin, methotrexate, and azathioprine, can be considered. However, relapse and side effects could still occur. The pathogenesis of AD involves epidermal barrier dysfunction, skin microbiome abn...
Source: BioDrugs - July 1, 2021 Category: Drugs & Pharmacology Source Type: research

Comparability of Biologics: Global Principles, Evidentiary Consistency and Unrealized Reliance
AbstractThe principles of comparability assessments have been accepted globally as offering sensitive and reliable tools with which to evaluate potential changes to biologics that may arise either through processing changes or through the creation of a copy (biosimilar) by a different sponsor. The comparability approach has evolved through systematic advances in four areas: clear and convergent guidelines for evaluation of potential changes to biologics; risk-based systems of weighting analytical data; progressive improvements in analytical methods; and advanced understanding of post-translational modifications. Routine re...
Source: BioDrugs - July 1, 2021 Category: Drugs & Pharmacology Source Type: research