1,146 results match your criteria BioDrugs[Journal]


Lanadelumab for the Prophylactic Treatment of Hereditary Angioedema with C1 Inhibitor Deficiency: A Review of Preclinical and Phase I Studies.

BioDrugs 2018 Dec 12. Epub 2018 Dec 12.

Division of Rheumatology, Allergy and Immunology, University of California, San Diego, 8899 University Center Lane, Suite 230, San Diego, CA, 92122, USA.

Hereditary angioedema (HAE) with C1 esterase inhibitor (C1-INH) deficiency (C1-INH-HAE) is a rare disease characterized by diminished levels or dysfunctional activity of C1-INH, leading to dysregulated plasma kallikrein activity within the kallikrein-kinin pathway. Symptoms manifest as painful, potentially life-threatening swelling of subcutaneous tissues throughout the body and/or submucosal edema in the upper airway or gastrointestinal tract. Attacks recur with unpredictable frequency, intensity, and duration, placing a heavy burden on patients' daily lives. Read More

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December 2018

Comparison of the Pharmacokinetic-Pharmacodynamic Relationships of Two Darbepoetin Alfa Formulations in Healthy Male Volunteers.

BioDrugs 2018 Dec 1. Epub 2018 Dec 1.

Department of Clinical Pharmacology and Therapeutics, Samsung Medical Center, Seoul, Republic of Korea.

Objective: This study compared the pharmacokinetic (PK), pharmacodynamic (PD), and safety properties of the test (CJ-40001) and reference (NESP) versions of darbepoetin alfa following a single subcutaneous (SC) or intravenous (IV) administration in healthy male subjects.

Methods: A single-blind, randomized, single-dose, two-period, two-intervention crossover study was conducted, with two separate parts consisting of SC or IV administration. In each period, either a test or reference product was administered via the SC or IV route. Read More

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December 2018
5 Reads

A Phase I Study Comparing the Pharmacokinetics, Safety, and Immunogenicity of Proposed Biosimilar GB242 and Reference Infliximab in Healthy Subjects.

BioDrugs 2018 Dec 3. Epub 2018 Dec 3.

Department of Pharmacy, Peking University People's Hospital, Beijing, China.

Objective: The objective of this study was to compare the pharmacokinetics (PKs), safety, and immunogenicity of GB242 as a potential biosimilar infliximab with those of reference infliximab in healthy Chinese subjects.

Methods: We conducted a randomized, single-center, double-blind, parallel-controlled phase I study in which 48 healthy subjects were divided equally into a GB242 group and reference infliximab group. Both the test and reference drug were administered as a single intravenous dose of 3 mg/kg. Read More

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December 2018
1 Read
2.989 Impact Factor

Comparative Effectiveness and Safety of Monoclonal Antibodies (Bevacizumab, Cetuximab, and Panitumumab) in Combination with Chemotherapy for Metastatic Colorectal Cancer: A Systematic Review and Meta-Analysis.

BioDrugs 2018 Dec;32(6):585-606

Postgraduate Program in Medicines and Pharmaceutical Services, School of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, Brazil.

Background: The last decade has seen the increasing use of biological medicines in combination with chemotherapy containing 5-fluorouracil/oxaliplatin or irinotecan for the treatment of metastatic colorectal cancer (mCRC). These combinations have resulted in increased progression-free survival (PFS) in patients with mCRC; however, there are remaining concerns over the extent of their effect on overall survival (OS). Published studies to date suggest no major differences between the three currently available monoclonal antibodies (MoAbs); however, there are differences in costs. Read More

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December 2018
1 Read

Recombinant Antibody Production in CHO and NS0 Cells: Differences and Similarities.

BioDrugs 2018 Dec;32(6):571-584

Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, 21218, USA.

The commercial production of monoclonal antibodies (mAbs) has revolutionized the treatment of many diseases, including cancer, multiple sclerosis, and rheumatoid arthritis. These biotherapeutics have the potential to generate a global annual revenue of more than US$150 billion. Two cell hosts are predominantly utilized to produce these mAbs: Chinese hamster ovary (CHO) cells and murine myeloma cells (NS0). Read More

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December 2018
9 Reads

Targeting IL-6 or IL-6 Receptor in Rheumatoid Arthritis: What's the Difference?

BioDrugs 2018 Dec;32(6):531-546

Department of Rheumatology and Clinical Immunology, Charité-Universitätsmedizin, Berlin, Germany.

Interleukin-6 (IL-6) signaling is a critical target in inflammatory pathways. Today, tocilizumab (TCZ) and sarilumab (SAR), two IL-6 receptor-inhibiting monoclonal antibodies, are widely used in the treatment of rheumatoid arthritis (RA), with a favorable efficacy/safety profile. Successful introduction of such agents in the treatment of RA has encouraged the development of other agents targeting different points of the pathway. Read More

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December 2018

GP2017: An Adalimumab Biosimilar.

Authors:
Young-A Heo

BioDrugs 2018 Dec;32(6):635-638

Springer, Private Bag 65901, Mairangi Bay, Auckland, 0754, New Zealand.

GP2017 (adalimumab) is a biosimilar anti-TNF-α antibody. It is approved in the EU for use in all indications for which reference adalimumab is approved. GP2017 has similar physicochemical and functional properties to those of reference adalimumab, and the pharmacokinetic similarity of the agent has been shown in healthy male volunteers. Read More

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December 2018
15 Reads

Correction to: PF-06438179/GP1111: An Infliximab Biosimilar.

BioDrugs 2018 Dec;32(6):643

Springer, Private Bag 65901, Mairangi Bay, Auckland, 0754, New Zealand.

The article PF-06438179/GP1111: An Infliximab Biosimilar, written by Zaina T. Al-Salama. Read More

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December 2018

Bispecific Antibody Emicizumab for Haemophilia A: A Breakthrough for Patients with Inhibitors.

BioDrugs 2018 Dec;32(6):561-570

Hemophilia Comprehensive Care Centre, Charlotte Maxeke Johannesburg Academic Hospital and Faculty of Health Sciences, University of the Witwatersrand and NHLS, 7 York Road, Parktown, Johannesburg, 2193, South Africa.

Current unmet needs in haemophilia A patients with inhibitors include the need for intravenous infusion of replacement therapy and the high burden of treatment associated with prophylaxis. Emicizumab is a humanised bispecific monoclonal antibody designed to address these unmet needs and has completed phase III clinical trials in adolescents/adults (HAVEN 1) and paediatric (HAVEN 2) inhibitor populations. In HAVEN 1, there was an 80% bleed reduction across all bleeds, 89% reduction in treated joint bleeds, 92% reduction in treated spontaneous bleeds, and 95% reduction in treated target joint bleeds on emicizumab compared with no prophylaxis. Read More

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December 2018
2 Reads

In-Use Physicochemical and Biological Stability of the Trastuzumab Biosimilar CT-P6 Upon Preparation for Intravenous Infusion.

BioDrugs 2018 Dec;32(6):619-625

R&D Division, Biotechnology Research Institute, Celltrion Inc., Incheon, Korea.

Background: CT-P6 is a biosimilar of trastuzumab, a monoclonal antibody targeting human epidermal growth factor 2 (HER2), that is used in the treatment of breast and gastric cancers.

Objective: The aim of this study was to evaluate the in-use physicochemical and biological stability of CT-P6 following preparation for intravenous (IV) infusion.

Methods: One batch of CT-P6 within the final month of its 48-month shelf life was used to simulate sub-optimal administration conditions. Read More

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December 2018
7 Reads

Real World Data on the Utilization Pattern and Safety Profile of Infliximab Originator Versus Biosimilars in Italy: A Multiregional Study.

BioDrugs 2018 Dec;32(6):607-617

Campania Pharmacovigilance and Pharmacoepidemiology Regional Centre, Section of Pharmacology "L. Donatelli", Department of Experimental Medicine, University of Campania "L. Vanvitelli", Naples, Italy.

Background: In recent years, several biosimilar drugs, including those of infliximab, have obtained marketing authorization from the European Medicines Agency (EMA). Given the peculiarity of the safety profile of biological medical products (originator and biosimilars), the evaluation of their tolerability represents an important component of pre-marketing and post-marketing clinical development. For example, infliximab products may cause adverse drug reactions (ADRs) including acute infusion reactions, delayed hypersensitivity reactions, and loss of efficacy, as a direct consequence of immunogenicity. Read More

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December 2018
3 Reads

Emerging Technologies for Delivery of Biotherapeutics and Gene Therapy Across the Blood-Brain Barrier.

BioDrugs 2018 Dec;32(6):547-559

Human Health Therapeutics Research Centre, Translational Bioscience, National Research Council Canada, 1200 Montreal Road, Ottawa, ON, Canada.

Antibody, immuno- and gene therapies developed for neurological indications face a delivery challenge posed by various anatomical and physiological barriers within the central nervous system (CNS); most notably, the blood-brain barrier (BBB). Emerging delivery technologies for biotherapeutics have focused on trans-cellular pathways across the BBB utilizing receptor-mediated transcytosis (RMT). 'Traditionally' targeted RMT receptors, transferrin receptor (TfR) and insulin receptor (IR), are ubiquitously expressed and pose numerous translational challenges during development, including species differences and safety risks. Read More

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December 2018
5 Reads

Darvadstrocel: A Review in Treatment-Refractory Complex Perianal Fistulas in Crohn's Disease.

Authors:
Lesley J Scott

BioDrugs 2018 Dec;32(6):627-634

Springer, Private Bag 65901, Mairangi Bay, Auckland, 0754, New Zealand.

Darvadstrocel (Alofisel) consists of a suspension of expanded human allogeneic adipose-derived mesenchymal stem cells (eASCs). It is the first mesenchymal stem cell (MSC) advanced therapy approved in the EU for the treatment of complex perianal fistulas in adult patients with non-active/mildly active luminal Crohn's disease, when fistulas have shown an inadequate response to ≥ 1 conventional or biologic therapy. In the pivotal phase 3 ADMIRE-CD trial in this difficult-to-treat patient population, after standard-of-care fistula conditioning, add-on therapy with a single dose of darvadstrocel (120 million eASC) administered into the tissue surrounding complex perianal fistulas was significantly more effective than placebo (saline), with the darvadstrocel group having a higher combined remission rate (i. Read More

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December 2018
4 Reads

PF-06438179/GP1111: An Infliximab Biosimilar.

BioDrugs 2018 Dec;32(6):639-642

Springer, Private Bag 65901, Mairangi Bay, Auckland, 0754, New Zealand.

PF-06438179/GP1111 (Zessly; Ixifi) [hereafter referred to as GP1111] is a biosimilar of the reference monoclonal anti-TNF-α antibody infliximab, and is approved in the EU and USA for the same indications as the reference drug, including rheumatoid arthritis (RA), Crohn's disease, ulcerative colitis (including paediatric ulcerative colitis in the EU), ankylosing spondylitis, psoriatic arthritis and plaque psoriasis; GP1111 is also approved in Japan. GP1111 has similar physicochemical characteristics and pharmacodynamic properties to those of reference infliximab, and the pharmacokinetic similarity of the agents has been shown in healthy volunteers and patients with moderate-to-severe RA despite methotrexate therapy. GP1111 demonstrated clinical efficacy equivalent to that of reference infliximab in patients with moderate-to-severe RA, despite methotrexate therapy, and was generally well tolerated in this population. Read More

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December 2018
2 Reads

PF-05280014: A Trastuzumab Biosimilar.

Authors:
Julia Paik

BioDrugs 2018 Oct;32(5):515-518

Springer, Private Bag 65901, Mairangi Bay, Auckland, 0754, New Zealand.

PF-05280014 (Trazimera™) is the fourth biosimilar of the reference anti-HER2 antibody trastuzumab to be approved in the EU. It is approved for use in all indications for which reference trastuzumab is approved, including HER2-positive metastatic or early breast cancer and metastatic gastric cancer. PF-05280014 has similar physicochemical and pharmacodynamic properties to those of reference trastuzumab, and the pharmacokinetic similarity of the agents has been shown in women with metastatic or early HER2-positive breast cancer and healthy male volunteers. Read More

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October 2018
17 Reads

Non-pharmacological Effects in Switching Medication: The Nocebo Effect in Switching from Originator to Biosimilar Agent.

BioDrugs 2018 Oct;32(5):397-404

Hospital Pharmacy, Erasmus University Medical Center, Rotterdam, The Netherlands.

The nocebo effect is defined as the incitement or the worsening of symptoms induced by any negative attitude from non-pharmacological therapeutic intervention, sham, or active therapies. When a patient anticipates a negative effect associated with an intervention, medication or change in medication, they may then experience either an increase in this effect or experience it de novo. Although less is known about the nocebo effect compared with the placebo effect, widespread interest in the nocebo effect observed with statin therapy and a literature review highlighting the nocebo effect across at least ten different disease areas strongly suggests this is a common phenomenon. Read More

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October 2018
1 Read

ABP 980: A Trastuzumab Biosimilar.

Authors:
Sohita Dhillon

BioDrugs 2018 Oct;32(5):511-514

Springer, Private Bag 65901, Mairangi Bay, Auckland, 0754, New Zealand.

ABP 980 (KANJINTI™) is a biosimilar of the reference anti-HER2 antibody trastuzumab. In the EU, ABP 980 is approved for use in all indications for which reference trastuzumab is approved, including HER2-positive early breast cancer, metastatic breast cancer and metastatic gastric cancer. ABP 980 has similar physicochemical and functional properties to those of reference trastuzumab, and the pharmacokinetic biosimilarity of the agents has been shown in healthy subjects. Read More

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October 2018
12 Reads

SB5: An Adalimumab Biosimilar.

Authors:
James E Frampton

BioDrugs 2018 Oct;32(5):507-510

Springer, Private Bag 65901, Mairangi Bay, Auckland, 0754, New Zealand.

SB5 (Imraldi) is a biosimilar of the reference anti-TNF monoclonal antibody adalimumab. It is approved for use in the following indications for which reference adalimumab is approved: rheumatoid arthritis (RA), juvenile idiopathic arthritis [polyarticular juvenile idiopathic arthritis (pJIA) and enthesitis-related arthritis (ERA)], axial spondyloarthritis [ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nr-axSpA)], psoriatic arthritis (PsA), psoriasis, pediatric plaque psoriasis, hidradenitis suppurativa (HS), Crohn's disease, pediatric Crohn's disease, ulcerative colitis (UC), and non-infectious uveitis. SB5 has similar physicochemical and pharmacodynamic properties to those of reference adalimumab, and the pharmacokinetic similarity of these agents has been shown in healthy volunteers and patients with RA. Read More

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October 2018
2 Reads

Risk of Adverse Drug Events Observed with Baricitinib 2 mg Versus Baricitinib 4 mg Once Daily for the Treatment of Rheumatoid Arthritis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BioDrugs 2018 Oct;32(5):415-423

Department of Internal Medicine Education, The First Affiliated Hospital, Guangxi Medical University, Nanning, 530021, Guangxi, China.

Background: On 23 April 2018, the Food and Drug Administration-based Advisory Committee approved the use of baricitinib 2 mg for the treatment of rheumatoid arthritis and suggested the possibility of serious adverse events associated with baricitinib 4 mg. Hence, we aimed to systematically compare the risk of adverse drug events observed with baricitinib 2 mg versus 4 mg for the treatment of patients with rheumatoid arthritis.

Methods: Electronic databases including the Cochrane library, MEDLINE, EMBASE and http://www. Read More

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October 2018
7 Reads

Small-Molecule Immune Checkpoint Inhibitors Targeting PD-1/PD-L1 and Other Emerging Checkpoint Pathways.

BioDrugs 2018 Oct;32(5):481-497

Aurigene Discovery Technologies Limited, Bangalore, India.

Advances in harnessing the immune system for cancer treatment have been spectacular in recent years as witnessed by the approval of a number of antibodies targeting the PD-1/PD-L1 immune checkpoint pathway spanning an expanding list of indications. However, it is well recognized that while these antibodies show impressive clinical activity, they suffer from shortcomings including the failure to show response in a majority of patients, their need to be administered by intravenous injection, and immune-related adverse events due to the breaking of immune self-tolerance. Small-molecule-based therapeutic approaches offer the potential to address the shortcomings of these antibody-based checkpoint inhibitors. Read More

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October 2018
23 Reads

Ensuring Product Quality, Consistency and Patient Supply over Time for a Large-Volume Biologic: Experience with Remicade.

BioDrugs 2018 Oct;32(5):405-414

Janssen Research & Development, LLC, Malvern, PA, USA.

Biologics are produced from living organisms in complex, multi-stage manufacturing processes and contain inherent variability, which must be understood and controlled during manufacturing to avoid unexpected changes in key quality attributes that may contribute to clinically meaningful differences. The process must also meet large commercial demand, while simultaneously being able to accommodate change without sacrificing product consistency. The four key components of successful biologics manufacturing are (1) a stable, well-defined proprietary cell line; (2) a good manufacturing practice (GMP)-compliant supply chain with a process control strategy defining acceptable levels of variability for target product/process attributes and capable of managing complex material flows; (3) a tightly controlled procedure for implementation of proposed process changes that ensures product consistency; and (4) built-in redundancy and flexibility providing the ability to adapt rapidly to unexpected developments. Read More

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October 2018
6 Reads

Expanding the Boundaries of Biotherapeutics with Bispecific Antibodies.

BioDrugs 2018 Oct;32(5):441-464

Protein Chemistry Department, Genentech Inc., South San Francisco, CA, 94080, USA.

Bispecific antibodies have moved from being an academic curiosity with therapeutic promise to reality, with two molecules being currently commercialized (Hemlibra and Blincyto) and many more in clinical trials. The success of bispecific antibodies is mainly due to the continuously growing number of mechanisms of actions (MOA) they enable that are not accessible to monoclonal antibodies. One of the earliest MOA of bispecific antibodies and currently the one with the largest number of clinical trials is the redirecting of the cytotoxic activity of T-cells for oncology applications, now extending its use in infective diseases. Read More

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October 2018
13 Reads

Pharmacokinetic and Immunological Considerations for Expanding the Therapeutic Window of Next-Generation Antibody-Drug Conjugates.

BioDrugs 2018 Oct;32(5):465-480

Department of Chemical Engineering, University of Michigan, 2800 Plymouth Rd, Ann Arbor, MI, 48109, USA.

Antibody-drug conjugate (ADC) development has evolved greatly over the last 3 decades, including the Food and Drug Administration (FDA) approval of several new drugs. However, translating ADCs from the design stage and preclinical promise to clinical success has been a major hurdle for the field, particularly for solid tumors. The challenge in clinical development can be attributed to the difficulty in connecting the design of these multifaceted agents with the impact on clinical efficacy, especially with the accelerated development of 'next-generation' ADCs containing a variety of innovative biophysical developments. Read More

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October 2018
3 Reads

Biosimilar Knowledge Among Oncology/Hematology Team Members in Colorado, USA: An Educational Initiative and Follow-Up Survey.

BioDrugs 2018 Oct;32(5):499-506

Complex Mechanisms of Disease, Aging and Trauma (CMDAT) Research Foundation, PO Box 460722, Denver, CO, 80246, USA.

Background: No data exist regarding oncology/hematology team members' knowledge of and views on biosimilars in Colorado, USA. Published research has suggested that health professionals may have a poor understanding of many issues related to biosimilars.

Objectives: Our goal was to increase oncology/hematology team members' knowledge of biosimilars and then use an anonymous online survey to assess the knowledge gained. Read More

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October 2018
1 Read

Comment on "The End of Phase 3 Clinical Trials in Biosimilars Development?"

BioDrugs 2018 10;32(5):519-521

FDA Strategy and Regulatory Policy, Avalere Health Inc., Washington, DC, USA.

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October 2018
1 Read

Correction to: GP2015: An Etanercept Biosimilar.

Authors:
Emma D Deeks

BioDrugs 2018 10;32(5):525

Springer, Private Bag 65901, Mairangi Bay, Auckland, 0754, New Zealand.

The article GP2015: An Etanercept Biosimilar, written by Emma D. Deeks, was originally published Online First without open access. After publication in volume 31, issue 6, pages 555-558 HEXAL AG requested that the article be Open Choice to make the article an open access publication. Read More

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October 2018
2 Reads

Subcutaneous Administration of Biotherapeutics: An Overview of Current Challenges and Opportunities.

BioDrugs 2018 Oct;32(5):425-440

Product Optimization, Global Product Strategy, F. Hoffmann-La Roche Ltd, Grenzacher Strasse 124, 4070, Basel, Switzerland.

Subcutaneous delivery of biotherapeutics has become a valuable alternative to intravenous administration across many disease areas. Although the pharmacokinetic profiles of subcutaneous and intravenous formulations differ, subcutaneous administration has proven effective, safe, well-tolerated, generally preferred by patients and healthcare providers and to result in reduced drug delivery-related healthcare costs and resource use. The aim of this article is to discuss the differences between subcutaneous and intravenous dosing from both health-economic and scientific perspectives. Read More

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October 2018
1 Read

Comparative Safety of Originator and Biosimilar Epoetin Alfa Drugs: An Observational Prospective Multicenter Study.

BioDrugs 2018 Aug;32(4):367-375

Pharmacology Unit, Department of Diagnostics and Public Health, University of Verona, Verona, Italy.

Background: Erythropoiesis-stimulating agents (ESAs) are biological molecules approved for the treatment of anemia associated with chronic renal failure. Biosimilars were licensed for use in Europe in 2007.

Aim: This study aimed to compare the safety profile of biosimilars with respect to the reference product in a nephrology setting. Read More

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August 2018
3 Reads

Regenerative Therapies for Parkinson's Disease: An Update.

BioDrugs 2018 Aug;32(4):357-366

John van Geest Centre for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, E.D. Adrian Building, Forvie Site, Robinson Way, Cambridge, CB2 0PY, UK.

Parkinson's disease is the second most common neurodegenerative disorder. It is characterised by a typical movement disorder that occurs in part because of the selective degeneration of the dopaminergic neurons of the substantia nigra pars compacta. Current treatment for the motor disorder of Parkinson's disease consists of dopaminergic medications, but these come with significant adverse effects, themselves an important part of the clinical course of Parkinson's disease, particularly in advanced stages. Read More

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August 2018
4 Reads

Pegvaliase: First Global Approval.

Authors:
Anthony Markham

BioDrugs 2018 Aug;32(4):391-395

Springer, Mairangi Bay, Private Bag 65901, Auckland, 0754, New Zealand.

BioMarin Pharmaceutical is developing pegvaliase (PALYNZIQ™) as a treatment for phenylketonuria, a genetic disorder caused by deficiency of phenylalanine hydroxylase which leads to neurotoxic accumulation of phenylalanine. Data from the phase III PRISM clinical trial program indicate treatment with pegvaliase is associated with sustained reductions in blood phenylalanine levels and sustained improvements in neurological sequelae in patients with phenylketonuria. Based on these positive results pegvaliase was recently approved in the US for adults with phenylketonuria who have uncontrolled blood phenylalanine concentrations on current treatment. Read More

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August 2018
3 Reads

Determination of Similarity Margin in Comparative Clinical Studies to Support the Development of Biosimilar Products of Neupogen (Filgrastim, Granulocyte Colony-Stimulating Factor [G-CSF]).

BioDrugs 2018 Jul 13. Epub 2018 Jul 13.

Division of Biometrics IV, OB/OTS/CDER/FDA, Silver Spring, MD, 20993-0002, USA.

To demonstrate a biological product is biosimilar to a reference product, the applicant needs to show that the product is highly similar and has no clinically meaningful differences. Comparative clinical studies are often conducted to support the conclusion of no clinically meaningful differences, as a part of totality of evidence. The FDA has published several guidance documents to facilitate the development of biosimilar products. Read More

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July 2018
4 Reads

Indoleamine 2,3-Dioxygenase (IDO) Inhibition as a Strategy to Augment Cancer Immunotherapy.

BioDrugs 2018 Aug;32(4):311-317

Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan Health System, 1500 E. Medical Center Drive, C369 Med Inn Building, SPC 5848, Ann Arbor, MI, 48109, USA.

Indoleamine 2,3-dioxygenase (IDO) is an enzyme of interest in immuno-oncology because of the immunosuppressive effects that result from its role in tryptophan catabolism. IDO is upregulated in malignancy and is associated with poor prognosis in multiple cancer types. IDO inhibitors have been developed to target IDO, both directly and indirectly. Read More

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August 2018
3 Reads

Spherical Nucleic Acid Nanoparticles: Therapeutic Potential.

BioDrugs 2018 Aug;32(4):297-309

Biomedical Engineering, University of Delaware, Newark, DE, 19716, USA.

Spherical nucleic acids (SNAs) are highly oriented, well organized, polyvalent structures of nucleic acids conjugated to hollow or solid core nanoparticles. Because they can transfect many tissue and cell types without toxicity, induce minimum immune response, and penetrate various biological barriers (such as the skin, blood-brain barrier, and blood-tumor barrier), they have become versatile tools for the delivery of nucleic acids, drugs, and proteins for various therapeutic purposes. This article describes the unique structures and properties of SNAs and discusses how these properties enable their application in gene regulation, immunomodulation, and drug and protein delivery. Read More

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August 2018
2 Reads

Oligonucleotide-Based Therapies for Inflammatory Bowel Disease.

BioDrugs 2018 Aug;32(4):331-338

Department of Systems Medicine, University of Rome Tor Vergata, Via Montpellier, 1, 00133, Rome, Italy.

The growing understanding of the immunopathogenesis of inflammatory bowel diseases (IBDs) has contributed to the identification of new targets whose expression/activity can be modulated for therapeutic purposes. Several approaches have been employed to develop selective pharmaceutical compounds; among these, antisense oligonucleotides (ASOs) or synthetic oligonucleotides represent a valid option for inhibiting or enhancing, respectively, the expression/function of molecules that have been implicated in the control of IBD-related inflammation. In this context, data have been accumulated for the following compounds: alicaforsen, an ASO targeting intercellular adhesion molecule-1, a transmembrane glycoprotein that regulates rolling and adhesion of leukocytes to inflamed intestine; DIMS0150 and BL-7040, two oligonucleotides that enhance Toll-like receptor-9 activity; Mongersen, an ASO that inhibits Smad7, thereby restoring transforming growth factor-β1/Smad-associated signaling; STNM01, a double-stranded RNA oligonucleotide silencing carbohydrate sulfotransferase, an enzyme involved in fibrogenic processes, and hgd40, a specific DNAzyme inhibiting expression of the transcription factor GATA3. Read More

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August 2018
3 Reads

The End of Phase 3 Clinical Trials in Biosimilars Development?

BioDrugs 2018 Aug;32(4):319-324

, Paris, France.

Most patients still have limited or no access to life-changing therapeutic proteins in the treatment of their cancer or autoimmune disorders. The current clinical development model of biosimilars is expensive, and in most cases, large, phase 3 trials do not provide meaningful information on the clinical equivalence of biosimilars and reference compounds. At the same time, the development of state-of-the-art orthogonal analytical methods has enabled a better understanding of the structure and structure-function relationship of biotherapeutics. Read More

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August 2018
17 Reads

Therapeutic Monoclonal Antibodies to Complex Membrane Protein Targets: Antigen Generation and Antibody Discovery Strategies.

BioDrugs 2018 Jun 23. Epub 2018 Jun 23.

Department of Antibody Discovery and Protein Engineering, MedImmune Ltd, Milstein Building, Granta Park, Cambridge, CB21 6GH, UK.

Cell surface membrane proteins comprise a wide array of structurally and functionally diverse proteins involved in a variety of important physiological and homeostatic processes. Complex integral membrane proteins, which are embedded in the lipid bilayer by multiple transmembrane-spanning helices, are represented by families of proteins that are important target classes for drug discovery. Such protein families include G-protein-coupled receptors, ion channels and transporters. Read More

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June 2018
10 Reads

Safety of Biologics Approved for the Treatment of Rheumatoid Arthritis and Other Autoimmune Diseases: A Disproportionality Analysis from the FDA Adverse Event Reporting System (FAERS).

BioDrugs 2018 Jun 5. Epub 2018 Jun 5.

Department of Pharmacy, Pharmaceutical Sciences Postgraduate Research Program, Federal University of Paraná, Curitiba, Brazil.

Introduction: The molecular and pharmacological complexity of biologic disease-modifying antirheumatic drugs used for the management of rheumatoid arthritis (RA) favors the occurrence of adverse drug reactions (ADRs), which should be constantly monitored in post-marketing safety studies.

Objective: The aim of this study was to identify signals of disproportionate reporting (SDR) of clinical relevance related to the use of biologic drugs approved for RA and other autoimmune diseases.

Methods: All suspected ADRs registered in the FDA Adverse Event Reporting System between January 2003 and June 2016 were collected. Read More

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June 2018
5 Reads

Determining the Value of Two Biologic Drugs for Chronic Inflammatory Skin Diseases: Results of a Multi-Criteria Decision Analysis.

BioDrugs 2018 Jun;32(3):281-291

Fundación Weber, Majadahonda, Madrid, Spain.

Background And Objective: Multi-criteria decision analysis (MCDA) is a tool that systematically considers multiple factors relevant to health decision-making. The aim of this study was to use an MCDA to assess the value of dupilumab for severe atopic dermatitis compared with secukinumab for moderate to severe plaque psoriasis in Spain.

Method: Following the EVIDEM (Evidence and Value: Impact on DEcision Making) methodology, the estimated value of both interventions was obtained by means of an additive linear model that combined the individual weighting (between 1 and 5) of each criterion with the individual scoring of each intervention in each criterion. Read More

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June 2018
4 Reads

SB3 (Ontruzant): A Trastuzumab Biosimilar.

Authors:
Yvette N Lamb

BioDrugs 2018 Jun;32(3):293-296

Springer, Private Bag 65901, Mairangi Bay, Auckland, 0754, New Zealand.

SB3 (Ontruzant) is the first biosimilar of the reference anti-HER2 antibody trastuzumab to be approved in the EU. It is approved for use in all indications for which reference trastuzumab is approved, namely HER2-positive early breast cancer, metastatic breast cancer and metastatic gastric cancer. SB3 has similar physicochemical and pharmacodynamic properties to those of reference trastuzumab, and the pharmacokinetic biosimilarity of the agents has been shown in healthy volunteers and women with HER2-positive early or locally advanced breast cancer. Read More

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June 2018
4 Reads

Efficacy and Safety Outcomes for Originator TNF Inhibitors and Biosimilars in Rheumatoid Arthritis and Psoriasis Trials: A Systematic Literature Review.

BioDrugs 2018 Jun;32(3):193-199

Organización Médica de Investigación, Buenos Aires, Argentina.

Objective: Regulatory approval of biosimilar versions of originator biotherapeutics requires that new biological products be highly similar to originator products, with no clinically meaningful differences in safety, purity, and potency. In some trials of biosimilars of tumor necrosis factor inhibitors for the treatment of rheumatoid arthritis (RA) and plaque psoriasis (PsO), pre-specified margins for efficacy and safety have been met, but differences in treatment responses between pivotal originator trials and biosimilar trials have been noted. The objective of this systematic review was to examine these differences. Read More

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June 2018
9 Reads

Anticalin Proteins as Therapeutic Agents in Human Diseases.

BioDrugs 2018 Jun;32(3):233-243

Lehrstuhl für Biologische Chemie, Technische Universität München, Emil-Erlenmeyer-Forum 5, 85354, Freising (Weihenstephan), Germany.

Anticalin proteins are an emerging class of clinical-stage biopharmaceuticals with high potential as an alternative to antibodies. Anticalin molecules are generated by combinatorial design from natural lipocalins, which are abundant plasma proteins in humans, and reveal a simple, compact fold dominated by a central β-barrel, supporting four structurally variable loops that form a binding site. Reshaping of this loop region results in Anticalin proteins that can recognize and tightly bind a wide range of medically relevant targets, from small molecules to peptides and proteins, as validated by X-ray structural analysis. Read More

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June 2018
2 Reads

Therapeutic Targeting of the Interleukin-4/Interleukin-13 Signaling Pathway: In Allergy and Beyond.

BioDrugs 2018 May 7. Epub 2018 May 7.

Department of Clinical Microbiology and Immunology, Sackler Faculty of Medicine, Tel-Aviv University, Ramat Aviv, 69978, Tel-Aviv, Israel.

Inflammation triggered by interleukin-4 (IL-4)/IL-13 is mediated by IL-4 and IL-13 receptors that are present on multiple cell types, including epithelial cells, smooth muscle, fibroblasts endothelial cells and immune cells. IL-4 exerts its activities by interacting with two specific cell surface receptors: one designated the type 1 IL-4 receptor (IL-4R); the other designated the type 2 IL-4R, a receptor complex that is also the functional receptor for IL-13. "Traditionally," IL-4 and IL-13 have been studied in the context of T helper 2-associated immune responses (i. Read More

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May 2018
2 Reads

Knowledge of Adverse Drug Reaction Reporting and the Pharmacovigilance of Biological Medicines: A Survey of Healthcare Professionals in Ireland.

BioDrugs 2018 Jun;32(3):267-280

School of Pharmacy, University College Cork, Cork, Ireland.

Background: In Europe, changes to pharmacovigilance legislation, which include additional monitoring of medicines, aim to optimise adverse drug reaction (ADR) reporting systems. The legislation also makes provisions related to the traceability of biological medicines.

Objective: The objective of this study was to assess (i) knowledge and general experience of ADR reporting, (ii) knowledge, behaviours, and attitudes related to the pharmacovigilance of biologicals, and (iii) awareness of additional monitoring among healthcare professionals (HCPs) in Ireland. Read More

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June 2018
8 Reads

Tissue Engineering in Osteoarthritis: Current Status and Prospect of Mesenchymal Stem Cell Therapy.

Authors:
Gun-Il Im

BioDrugs 2018 Jun;32(3):183-192

Department of Orthopaedics, Research Institute for Integrative Regenerative Medical Engineering, Dongguk University Ilsan Hospital, 814 Siksa-Dong, Goyang, 410-773, Republic of Korea.

Osteoarthritis (OA) is the most common form of arthritis. Over the last 20 years, attempts have been made to regenerate articular cartilage to overcome the limitations of conventional treatments. As OA is generally associated with larger and diffuse involvement of articular surfaces and alteration of joint homeostasis, a tissue engineering approach for cartilage regeneration is more difficult than in simple chondral defects. Read More

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June 2018
2 Reads

Overcoming Tumor-Induced Immune Suppression: From Relieving Inhibition to Providing Costimulation with T Cell Agonists.

BioDrugs 2018 Jun;32(3):221-231

Earle A. Chiles Research Institute, Providence Portland Medical Center, 4805 NE Glisan St., 2N35, Portland, OR, 97213, USA.

Recent advancements in T-cell biology and antibody engineering have opened doors to significant improvements in cancer immunotherapy. Initial success with monoclonal antibodies targeting key receptors that inhibit T-cell function such as cytotoxic T lymphocyte antigen 4 (CTLA-4) and programmed death-ligand 1 (PD-1) have demonstrated the potency of this new class of therapy, highlighted by long-term complete responses for metastatic cancers once thought incurable. However, only a subset of patients responds to checkpoint blockade because of a multitude of factors, including an immunosuppressive tumor microenvironment and the mutational burden of the cancer. Read More

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June 2018
4 Reads

Benefit Versus Risk Assessment of Rotavirus Vaccination in France: A Simulation and Modeling Analysis.

BioDrugs 2018 Apr;32(2):139-152

Pharmaco-Epidemiology and Health Outcomes Research, Laboratoire GSK, Rueil-Malmaison, France.

Introduction: Two vaccines against rotavirus gastroenteritis (RVGE) in young children, Rotarix and RotaTeq, have been available in Europe since 2006. Vaccination against rotaviruses significantly reduces the burden of RVGE, but it is also associated with a very small increased risk of intussusception. In a benefit-risk analysis, the prevented RVGE burden is weighed against the possible excess of intussusception. Read More

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April 2018
12 Reads

Humanized Mouse Models for the Preclinical Assessment of Cancer Immunotherapy.

BioDrugs 2018 Jun;32(3):245-266

Department of Gynecology and Obstetrics, University Medical Center Regensburg, Landshuter Straße 65, 93053, Regensburg, Germany.

Immunotherapy is one of the most exciting recent breakthroughs in the field of cancer treatment. Many different approaches are being developed and a number have already gained regulatory approval or are under investigation in clinical trials. However, learning from the past, preclinical animal models often insufficiently reflect the physiological situation in humans, which subsequently causes treatment failures in clinical trials. Read More

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June 2018
5 Reads

Comprehensive Physicochemical and Biological Characterization of the Proposed Biosimilar Darbepoetin Alfa, LBDE, and Its Originator Darbepoetin Alfa, NESP.

BioDrugs 2018 Apr;32(2):153-168

Department of Biological Sciences, KAIST, 291 Daehak-ro, Yuseong-gu, Daejeon, 34141, Republic of Korea.

Background: For regulatory approval, the comparability of a biosimilar product to an originator product should be ensured through thorough physicochemical and biological characterization.

Objective: To evaluate the biosimilarity between LBDE, the proposed biosimilar darbepoetin alfa, and NESP, its originator, we performed a comprehensive physicochemical and biological characterization study.

Methods: Primary and higher-order protein structures were analyzed using Lys-C peptide mapping with liquid chromatography-mass spectrometry (LC-MS), disulfide bond identification, circular dichroism, and fluorescence spectroscopy. Read More

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April 2018
26 Reads

Interleukin-1 Blockade in Cardiovascular Diseases: From Bench to Bedside.

BioDrugs 2018 Apr;32(2):111-118

VCU Pauley Heart Center, Virginia Commonwealth University, 1200 E Broad St, Box 980204, Richmond, VA, 23298, USA.

Interleukin-1 (IL-1) is the prototypical pro-inflammatory cytokine that occupies an apical place in the inflammatory cascade and also modulates cardiac function, functioning as a soluble cardiodepressant factor. Preclinical research over the past 4 decades has shown that blocking IL-1 processing or activity favorably affects cardiomyocyte survival and cardiac function in experimental animal models, paving the way for clinical studies in patients with heart disease. The promising results of phase II clinical trials of IL-1 blockade in patients with acute myocardial infarction and heart failure have been followed by a successful phase III trial in patients with prior acute myocardial infarction. Read More

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April 2018
5 Reads
2.990 Impact Factor