Current Issue : April - June Volume : 2014 Issue Number : 2 Articles : 5 Articles
Biosimilar Act, passed in 2007 under 351(k), states that a biosimilar product should be ââ?¬Å?highly similarââ?¬Â to prior\r\napproved reference product (RLD) and will have ââ?¬Å?no clinically meaningful differencesââ?¬Â in their safety or efficacy.\r\nFDA also published three guidances to support this biosimilar project. However, the biosimilar processes are not so\r\nsmooth. The biological molecules, manufacturing processes, and impurities profiles are complex; leaving various\r\nissues in deriving different sections of CMC work. Due to relative complexities in producing biosimilar product small\r\ndifferences in the design and execution of manufacturing process can have a large influence of product related-,\r\nprocess related-,or host related impurities protein profile of a finished product, which may trigger immunogenicity and\r\nchanges the clinical profile requiring elaborate animal studies and human clinical studies. FDAââ?¬â?¢s guidance is not very\r\nclear to drive the product into regulatory pathway for approval. Complexities still exist in clinical studies as clinicians\r\nlike to review the details of data from three phase 3 trials and payors wish to see more stringent data regarding\r\nsafety and efficacy. However, EMA developed a centralized path for the approval of Biosimilar product and so far\r\nEMA approved 16 products.\r\nOne of the remedies is that if the biosimilar product is purified to homogeneity or near homogeneity, and if it is\r\nstabilized and restores the functional activities, the impurities protein content will be negligible or minimum, which may\r\nnot trigger the immunogenicityor other clinical issues. With more advancement of science, research and development\r\nmay solve these issues and open the easier regulatory pathway for biosimilar approval. Interchangeability and price\r\nreduction issues may be solved at that time....
Background: Since 1995, approval for many new medicinal products has been obtained through a centralized\r\nprocedure in the European Union. In recent years, the use of summary measures of population health has become\r\nwidespread. We investigated whether efforts to develop innovative medicines are focusing on the most relevant\r\nconditions from a global public health perspective.\r\nMethods: We reviewed the information on new medicinal products approved by centralized procedure from 1995\r\nto 2009, information that is available to the public in the European Commission Register of medicinal products and\r\nthe European Public Assessment Reports from the European Medicines Agency. Morbidity and mortality data were\r\nincluded for each disease group, according to the Global Burden of Disease project. We evaluated the association\r\nbetween authorized medicinal products and burden of disease measures based on disability-adjusted life years\r\n(DALYs) in the European Union and worldwide.\r\nResults: We considered 520 marketing authorizations for medicinal products and 338 active ingredients. New\r\nauthorizations were seen to increase over the period analyzed. There was a positive, high correlation between\r\nDALYs and new medicinal product development (r = 0.619, p = 0.005) in the European Union, and a moderate\r\ncorrelation for middle-low-income countries (r = 0.497, p = 0.030) and worldwide (r = 0.490, p = 0.033). The most\r\nneglected conditions at the European level (based on their attributable health losses) were neuropsychiatric\r\ndiseases, cardiovascular diseases, respiratory diseases, sense organ conditions, and digestive diseases, while globally,\r\nthey were perinatal conditions, respiratory infections, sense organ conditions, respiratory diseases, and digestive\r\ndiseases.\r\nConclusions: We find that the development of new medicinal products is higher for some diseases than others.\r\nPharmaceutical industry leaders and policymakers are invited to consider the implications of this imbalance by\r\nestablishing work plans that allow for the setting of future priorities from a public health perspective...
Background: Anemia is a risk factor for death, adverse cardiovascular outcomes and poor quality of life in patients with\r\nchronic kidney disease (CKD). Erythropoietin Stimulating Agents (ESA) are commonly used to increase hemoglobin\r\nlevels in this population. In observational studies, higher hemoglobin levels (around 11-13 g/dL) are associated with\r\nimproved survival and quality of life compared to hemoglobin levels around 9-10 g/dL. A systematic review of\r\nrandomized trials found that targeting higher hemoglobin levels with ESA causes an increased risk of adverse vascular\r\noutcomes. It is possible, but has never been formally tested in a randomized trial, that ESA dose rather than targeted\r\nhemoglobin concentration itself mediates the increased risk of adverse vascular outcomes. The Clinical Evaluation of\r\nthe DOSe of Erythropoietins (C.E. DOSE) trial will assess the benefits and harms of a high versus a low fixed ESA dose for\r\nthe management of anemia in patients with end stage kidney disease.\r\nMethods/Design: This is a randomized, prospective open label blinded end-point (PROBE) trial due to enrol 2204\r\nhemodialysis patients in Italy. Patients will be randomized 1:1 to 4000 IU/week versus 18000 IU/week of intravenous\r\nepoietin alfa or beta, or any other ESA in equivalent doses. The dose will be adjusted only if hemoglobin levels fall\r\noutside the 9.5-12.5 g/dL range. The primary outcome will be a composite of all-cause mortality, non fatal stroke, non\r\nfatal myocardial infarction and hospitalization for cardiovascular causes. Quality of life and costs will also be assessed.\r\nDiscussion: The C.E.DOSE study will help inform the optimal therapeutic strategy for the management of anemia of\r\nhemodialysis patients, improving clinical outcomes, quality of life and costs, by ascertaining the potential benefits and\r\nharms of different fixed ESA doses....
Pricing and reimbursement of orphan drugs are an issue of high priority for policy makers, legislators, health care\r\nprofessionals, industry leaders, academics and patients. This study aims to conduct a literature review to provide\r\ninsight into the drivers of orphan drug pricing and reimbursement.\r\nAlthough orphan drug pricing follows the same economic logic as drug pricing in general, the monopolistic\r\npower of orphan drugs results in high prices: a) orphan drugs benefit from a period of marketing exclusivity; b)\r\nfew alternative health technologies are available; c) third-party payers and patients have limited negotiating power;\r\nd) manufacturers attempt to maximise orphan drug prices within the constraints of domestic pricing and\r\nreimbursement policies; and e) substantial R&D costs need to be recouped from a small number of patients.\r\nAlthough these conditions apply to some orphan drugs, they do not apply to all orphan drugs. Indeed, the small\r\nnumber of patients treated with an orphan drug and the limited economic viability of orphan drugs can be\r\nquestioned in a number of cases. Additionally, manufacturers have an incentive to game the system by artificially\r\ncreating monopolistic market conditions.\r\nGiven their high price for an often modest effectiveness, orphan drugs are unlikely to provide value for money.\r\nHowever, additional criteria are used to inform reimbursement decisions in some countries. These criteria may\r\ninclude: the seriousness of the disease; the availability of other therapies to treat the disease; and the cost to the\r\npatient if the medicine is not reimbursed. Therefore, the maximum cost per unit of outcome that a health care\r\npayer is willing to pay for a drug could be set higher for orphan drugs to which society attaches a high social\r\nvalue.\r\nThere is a need for a transparent and evidence-based approach towards orphan drug pricing and reimbursement.\r\nSuch an approach should be targeted at demonstrating the relative effectiveness, cost-effectiveness and economic\r\nviability of orphan drugs with a view to informing pricing and reimbursement decisions....
Background: Nivestimââ??¢ (filgrastim) is a follow-on biologic agent licensed in the EU for the treatment of neutropenia\r\nand febrile neutropenia induced by myelosuppressive chemotherapy. Nivestimââ??¢ has been studied in phase 2\r\nand 3 clinical trials where its efficacy and safety was found to be similar to its reference product, NeupogenÃ?®.\r\nFollow-on biologics continue to be scrutinised for safety. We present a design for two observational phase IV\r\nstudies that are evaluating the safety profile of Nivestimââ??¢ for the prevention and treatment of febrile neutropenia\r\n(FN) in patients treated with cytotoxic chemotherapy in general clinical practice.\r\nMethods/Design: The NEXT (TolÃ?©rance de Nivestim chez les patiEnts traitÃ?©s par une chimiothÃ?©rapie anticancÃ?©reuse\r\ncytotoXique en praTique courante) and VENICE (VErtrÃ?¤glichkeit von NIvestim unter zytotoxischer Chemotherapie in\r\nder Behandlung malinger Erkrankungen) trials are multicentre, prospective, longitudinal, observational studies\r\nevaluating the safety profile of Nivestimââ??¢ in ââ?¬Ë?real-worldââ?¬â?¢ clinical practice. Inclusion criteria include patients\r\nundergoing cytotoxic chemotherapy for malignancy and receiving Nivestim as primary or secondary prophylaxis\r\n(NEXT and VENICE), or as treatment for ongoing FN (NEXT only). In accordance with European Union\r\npharmacovigilance guidelines, the primary objective is to evaluate the safety of Nivestimââ??¢ by gathering data on\r\nadverse events in all system organ classes. Secondary objectives include obtaining information on patient\r\ncharacteristics, efficacy of Nivestimââ??¢ therapy (including chemotherapy dose intensity), patterns of use of Nivestimââ??¢,\r\nand physician knowledge regarding filgrastim prescription and the reasons for choosing Nivestimââ??¢. Data will be\r\ngathered at three visits: 1. At the initial inclusion visit, 2. At a 1-month follow-up visit, and 3. At the end of\r\nchemotherapy.\r\nRecruitment for VENICE commenced in July 2011 and in November 2011 for NEXT. VENICE completed recruitment\r\nin July 2013 with 407 patients, and NEXT in September 2013 with 2123 patients. Last patient, last visit for each\r\nstudy will be December 2013 and March 2014 respectively.\r\nDiscussion: The NEXT and VENICE studies will provide long-term safety, efficacy and practice pattern data in\r\npatients receiving Nivestimââ??¢ to support myelosuppressive chemotherapy in real world clinical practice. These data\r\nwill improve our understanding of the performance of Nivestimââ??¢ in patients encountered in the general patient\r\npopulation...
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