The effectiveness and value of eculizumab and efgartigimod for generalized myasthenia gravis.

DISCLOSURES: Funding for this summary was contributed by Arnold Ventures, The Donaghue Foundation, Harvard Pilgrim Health Care, and Kaiser Foundation Health Plan to the Institute for Clinical and Economic Review (ICER), an independent organization that evaluates the evidence on the value of health care interventions. ICER's annual policy summit is supported by dues from AbbVie, America's Health Insurance Plans, Anthem, Alnylam, AstraZeneca, Biogen, Blue Shield of CA, Boehringer-Ingelheim, Cambia Health Services, CVS, Editas, Evolve Pharmacy, Express Scripts, Genentech/Roche, GlaxoSmithKline, Harvard Pilgrim, Health Care Service Corporation, HealthFirst, Health Partners, Humana, Johnson & Johnson (Janssen), Kaiser Permanente, LEO Pharma, Mallinckrodt, Merck, Novartis, National Pharmaceutical Council, Pfizer, Premera, Prime Therapeutics, Regeneron, Sanofi, Sun Life Financial, uniQure, and United Healthcare. Agboola, Nikitin, and Pearson are employed by ICER. Through their affiliated institutions, Tice, Touchette, and Lien received funding from ICER for the work described in this summary.

[Biosimilars antibodies: positioning compared to originators - the experience in rheumatology and the biosimilars of trastuzumab in oncology]. / Anticorps biosimilaires versus princeps - L'expérience en rhumatologie et les biosimilaires du trastuzumab en oncologie.

Biosimilars have demonstrated their equivalence with biologic originators, according to rigorous specifications imposed by the regulatory agencies, the FDA and the EMA. Their development is justified by the very high cost of biopharmaceuticals, and strong incentives for their prescription lead us to hope substantial savings, allowing to finance other innovative molecules. Trastuzumab marked history of the treatment of breast cancer. Four biosimilars of trastuzumab are available for routine use and we will detail the key points of their development.

TITLE: Anticorps biosimilaires versus princeps - L'expérience en rhumatologie et les biosimilaires du trastuzumab en oncologie. ABSTRACT: Les biosimilaires sont des produits ayant montré leur équivalence avec le traitement biologique de référence, selon un cahier des charges strict imposé par les agences d'enregistrement, la FDA et l'EMA. Leur développement et leur utilisation sont justifiés par le coût très élevé des biomédicaments, et de fortes incitations à leur prescription font espérer des économies substantielles, permettant le financement d'autres molécules innovantes. Le trastuzumab a marqué l'histoire des traitements du cancer du sein, quatre biosimilaires étant désormais disponibles pour une utilisation en routine. Nous détaillerons ici les points clés de leur développement.

The path to VICTORy - a beginner's guide to success using commercial research antibodies.

Commercial research antibodies are crucial tools in modern cell biology and biochemistry. In the USA some $2 billion a year are spent on them, but many are apparently not fit-for-purpose, and this may contribute to the 'reproducibility crisis' in biological sciences. Inadequate antibody validation and characterization, lack of user awareness, and occasional incompetence amongst suppliers have had immense scientific and personal costs. In this Opinion, I suggest some paths to make the use of these vital tools more successful. I have attempted to summarize and extend expert views from the literature to suggest that sustained routine efforts should made in: (1) the validation of antibodies, (2) their identification, (3) communication and controls, (4) the training of potential users, (5) the transparency of original equipment manufacturer (OEM) marketing agreements, and (5) in a more widespread use of recombinant antibodies (together denoted the 'VICTOR' approach).

Cost-Effectiveness of Antibody-Based Induction Therapy in Deceased Donor Kidney Transplantation in the United States.

BACKGROUND: Induction therapy in deceased donor kidney transplantation is costly, with wide discrepancy in utilization and a limited evidence base, particularly regarding cost-effectiveness. METHODS: We linked the United States Renal Data System data set to Medicare claims to estimate cumulative costs, graft survival, and incremental cost-effectiveness ratio (ICER - cost per additional year of graft survival) within 3 years of transplantation in 19 450 deceased donor kidney transplantation recipients with Medicare as primary payer from 2000 to 2008. We divided the study cohort into high-risk (age > 60 years, panel-reactive antibody > 20%, African American race, Kidney Donor Profile Index > 50%, cold ischemia time > 24 hours) and low-risk (not having any risk factors, comprising approximately 15% of the cohort). After the elimination of dominated options, we estimated expected ICER among induction categories: no-induction, alemtuzumab, rabbit antithymocyte globulin (r-ATG), and interleukin-2 receptor-antagonist. RESULTS: No-induction was the least effective and most costly option in both risk groups. Depletional antibodies (r-ATG and alemtuzumab) were more cost-effective across all willingness-to-pay thresholds in the low-risk group. For the high-risk group and its subcategories, the ICER was very sensitive to the graft survival; overall both depletional antibodies were more cost-effective, mainly for higher willingness to pay threshold (US $100 000 and US $150 000). Rabbit ATG appears to achieve excellent cost-effectiveness acceptability curves (80% of the recipients) in both risk groups at US $50 000 threshold (except age > 60 years). In addition, only r-ATG was associated with graft survival benefit over no-induction category (hazard ratio, 0.91; 95% confidence interval, 0.84-0.99) in a multivariable Cox regression analysis. CONCLUSIONS: Antibody-based induction appears to offer substantial advantages in both cost and outcome compared with no-induction. Overall, depletional induction (preferably r-ATG) appears to offer the greatest benefits.

A high-value cost conscious approach to minimize heparin induced thrombocytopenia antibody (HITAb) testing using the 4T score.

Heparin Induced Thrombocytopenia (HIT) is a serious complication from administration of heparin products. The 4T score is a validated pre-test probability tool to screen for HIT in hospitalized patients. As the negative predictive value (NPV) is very high further testing for HIT in patients with a low score can be avoided. Our objective was to determine trends at our hospital with respect to utilization of HIT antibody (HITAb) testing and evaluate economic burden from unnecessary HIT testing. A retrospective cohort review was performed on patients age 18 and above admitted to a tertiary care center from February 2013 to December 2014 who underwent HITAb testing. Surgical ICU patients were excluded. Patients were stratified into low, intermediate, and high risk for HIT based on the 4T model. Statistical analysis was performed using Chi square and regression models. Of 150 patients that underwent HITAb testing, 134 met inclusion criteria. 73 were male (54.47 %) and mean age was 55.50 ± 17.27 years. 81 patients had a low 4T score 0-3. Analysis of testing trends showed 60.44 % of patients were tested for HITAb despite being low risk using the 4T model. Only three patients with low 4T score were positive on confirmatory SRA testing (NPV 96.29 % CI 95 = 89.56-99.23 %). Expenditure due to inappropriate testing and treatment was estimated at $103,348.13. The majority of HITAb testing was found unnecessary based on the investigator calculated 4T score. We propose implementation of an electronic medical record (EMR) based calculator in order to reduce unneeded tests and reduce use of costlier alternative anticoagulants.

Proposed minimal panel of antibodies for cost-effectiveness and accuracy in acute leukemias immunophenotyping: Prospective study at a tertiary care center.

INTRODUCTION: Flowcytometry has an essential role in the diagnosis and classification of acute leukemias. However, there exists a great degree of inter-laboratory variability on issues like panel selection, antibody combinations, gating strategies, fluorochromes, and clonal selection. AIM: The primary aim of this study was to derive a minimal panel of antibodies and evaluate its diagnostic usefulness in acute leukemias by flowcytometry by using the detailed immune-phenotype of different lineage-specific or non-specific markers. MATERIALS AND METHODS: This prospective observational study involved 400 newly diagnosed cases of acute leukemias. Bone marrow aspirate samples were subjected to morphological evaluation, cytogenetics and flow cytometric immunophenotyping. RESULTS: A minimal panel of eight antibodies comprising of CD45/CD34/CD19/MPO/cytoCD3/CD64/CD117/CD79a was derived by applying different permutations and combinations with a diagnostic yield of 97.5%. The minimal panel was further validated by testing in an independent cohort of patients with similar demographic characteristics, where it showed a high diagnostic yield of 98% in comparison with the screening panels proposed by other recently published studies. CONCLUSION: It may be concluded that the diagnostic performance of the eight antibody panel is better than most other panels used across the different laboratories in terms of yield, number of antibodies used and the scientific approach used to derive and validate the results and so henceforth may be applied in any setting with limited resources for better diagnostic accuracy.

Economics of recombinant antibody production processes at various scales: Industry-standard compared to continuous precipitation.

Standard industry processes for recombinant antibody production employ protein A affinity chromatography in combination with other chromatography steps and ultra-/diafiltration. This study compares a generic antibody production process with a recently developed purification process based on a series of selective precipitation steps. The new process makes two of the usual three chromatographic steps obsolete and can be performed in a continuous fashion. Cost of Goods (CoGs) analyses were done for: (i) a generic chromatography-based antibody standard purification; (ii) the continuous precipitation-based purification process coupled to a continuous perfusion production system; and (iii) a hybrid process, coupling the continuous purification process to an upstream batch process. The results of this economic analysis show that the precipitation-based process offers cost reductions at all stages of the life cycle of a therapeutic antibody, (i.e. clinical phase I, II and III, as well as full commercial production). The savings in clinical phase production are largely attributed to the fact that expensive chromatographic resins are omitted. These economic analyses will help to determine the strategies that are best suited for small-scale production in parallel fashion, which is of importance for antibody production in non-privileged countries and for personalized medicine.

[Development of antibody medicines by bio-venture: lesson from license negotiations with mega pharmacies].

The current method of antibody production is mainly the hybridoma method, in which mice are immunized with an excess amount of antigen for a short period to promote activation and proliferation of B-lymphocytes producing the antibodies of interest. Because of the excess antigen, those producing low-affinity antibodies are activated. In contrast, human blood B-lymphocytes are activated through natural immune reactions, such as the reaction to infection. B-lymphocytes are stimulated repeatedly with a small amount of antigen, and thus only those producing high-affinity antibodies are activated. Consequently, the lymphocytes producing the high-affinity antibodies are accumulated in human blood. Therefore, human lymphocytes are an excellent source of high-affinity antibodies. Evec, Inc. has established a unique method to produce high-affinity antibodies from human lymphocytes using Epstein-Barr virus (EBV), which induces the proliferation of B-lymphocytes. The method first induces the proliferation of B-lymphocytes from human blood using EBV, and then isolates those producing the antibodies of interest. The key features of the Evec technique are: 1) development of a lymphocyte library consisting of 150 donors' lymphocytes from which donors suited to develop the antibodies of interest can be selected in 4 days; and 2) development of a sorting method and cell microarray method for selecting lymphocyte clones producing the target antibodies. Licensing agreements have been concluded with European and Japanese pharmaceutical companies for two types of antibody. This paper describes Evec's antibody technology and experience in license negotiations with Mega Pharmacies.

CEE-ing is believing: bioscience ventures in Central and Eastern Europe.

Bioscience ventures in Central and Eastern Europe are becoming a presence in world healthcare markets despite a perennially short supply of venture funding and other support mechanisms relative to other world economic regions. Here are three up-and-coming CEE stories worth keeping an eye on.

An inexpensive thread-based system for simple and rapid blood grouping.

This study investigates the use of thread as a flexible and low-cost substrate for the rapid grouping of blood. The use of a capillary substrate such as thread for blood grouping utilises the sensitivity of the flow resistance of large particles in narrow capillary channels to separate agglutinated red blood cells (RBCs) from plasma. Large and discrete particles formed in a continuous liquid phase do not provide capillary wicking driving force and fall behind the capillary wicking front, leading to their separation from the wicking liquid. The capillary substrate therefore provides a very promising but different mechanism for the separation of the agglutinated RBCs and the blood serum phase compared to most existing blood grouping methods. The principle of chromatographic separation is also exploited in this study via the use of suitable dyes to enhance the visual detection of the agglutinated RBCs and the serum phase; surprising and encouraging outcomes are obtained. Using a thread-based device, the ABO and Rh groups can be successfully determined with only 2 µL of whole blood from a pricked finger tip within 1 min and without pre-treatment of the blood sample. It is hoped that a new, inexpensive, rapid and simple method may provide an easy-to-use blood grouping platform well suited to those in developing or remote regions of the world.

Cost effectiveness of respiratory syncytial virus prophylaxis: a critical and systematic review.

Respiratory syncytial virus (RSV) is the leading cause of infant hospitalization in the US. The economic burden of severe disease is substantial, including hospitalization costs and out-of-pocket expenses. RSV prophylaxis with either RSV immune globulin intravenous (RSV-IGIV) or palivizumab has been shown to be effective in reducing RSV-related hospitalizations. Motavizumab, a new enhanced-potency humanized RSV monoclonal antibody, is presently in clinical trials. RSV-IGIV and palivizumab are associated with high acquisition costs. Cost-effectiveness analyses are therefore of great importance in helping to determine who should receive RSV prophylaxis. Six studies have analysed the cost effectiveness of RSV-IGIV, 14 have analysed the cost effectiveness of palivizumab and five have analysed the cost effectiveness of both agents, two of which directly compared palivizumab with RSV-IGIV. The cost effectiveness of motavizumab has not been studied. Significant variation exists in the modelling used in these analyses. Many studies have examined short-term benefits such as reducing hospitalizations and associated costs, while fewer studies have examined long-term benefits such as QALYs or life-years gained. The payer and society have been the most common perspectives used. The endpoints examined varied and generally did not account for the potential impact of RSV prophylaxis on RSV-related complications such as asthma. While some studies have reported acceptable cost-effectiveness ratios for RSV prophylaxis, the majority failed to show cost savings or cost-effectiveness ratios below commonly accepted thresholds for either RSV-IGIV or palivizumab. Cost effectiveness of RSV prophylaxis tended to be more favourable in populations with specific risk factors, including premature infants < or =32 weeks' gestational age, and infants or children aged < 2 years with chronic lung disease or congenital heart disease. Comparing the results of economic analyses of the two agents suggests palivizumab may be the more cost-effective option in the population for which RSV prophylaxis is recommended. Over time, the acquisition cost of RSV prophylaxis agents, a major cost driver, may decrease, and more acceptable outcomes of economic analyses may result. Albeit important, the results of economic analyses are not the only tool that decision makers rely on, as population-specific risk factors, and efficacy and safety data must be considered when developing treatment guidelines and making clinical decisions.

Comparison of the Dako EGFR pharmDx kit and Zymed EGFR antibody for assessment of EGFR status in colorectal adenocarcinoma.

Immunohistochemistry is widely used to assess epidermal growth factor receptor (EGFR) expression on colorectal carcinomas to select patients for treatment with cetuximab, an anti-EGFR antibody. The data comparing different commercial EGFR antibodies is limited, and no cost comparisons have been made. We analyzed 65 advanced colorectal cancers from 36 patients using the EGFR pharmDx kit (DakoCytomation) and Clone 31G7 (Zymed Laboratories, Inc). EGFR expression was seen in 35 (53%) tumors (21 primary, 14 metastatic) with the Dako pharmDx kit. The Zymed antibody showed positive results in 41 (63%) tumors (25 primary, 16 metastatic). The cost per test was $40.00 with the pharmDx kit and $3.52 with the Zymed antibody. The Zymed antibody detects 10% more cases of colorectal cancer as EGFR positive, and is 10 times cheaper than the Dako pharmDx kit. There is little justification for the use of expensive kits for testing EGFR expression, when other available antibodies without the kit can give comparable or superior results.