Current Issue : January - March Volume : 2019 Issue Number : 1 Articles : 5 Articles
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Background: Chemotherapy-induced neutropenia is a common result of myelosuppressive chemotherapy treatment.\nInfections such as febrile neutropenia (FN) are sensitive to the duration of neutropenia as well as the depth of\nabsolute neutrophil count (ANC) at nadir. Filgrastim, a granulocyte colony stimulating factor (G-CSF), can stimulate\nthe function of mature neutrophils. Pegfilgrastim, a long-acting form of filgrastim, has been shown to reduce FN to a\ngreater extent compared to filgrastim. G-CSF agents have been recommended for prophylactic administration with\nchemotherapy. Apotex developed a proposed pegfilgrastim biosimilar. This study was conducted to confirm that\nno clinically meaningful efficacy or safety differences exist between Apotexâ??s proposed biosimilar and its reference\nproduct.\nMethods: 589 breast cancer patients were randomized and dosed with the proposed pegfilgrastim biosimilar, USlicensed\npegfilgrastim reference product, or EU-approved pegfilgrastim reference product. The primary endpoint\nassessed was the duration of severe neutropenia (DSN) and secondary endpoints included rate of FN and ANC nadir.\nResults: Data showed that the mean DSN, the primary endpoint measured, was comparable across all three treatments.\nThe As Treated arm had a 95% confidence interval within the equivalence range for the proposed pegfilgrastim\nbiosimilar with the US-licensed and EU-approved pegfilgrastim reference products. Secondary endpoints, which\nincluded depth and peak of ANC nadir, time to ANC recovery post-nadir and rates of FN, also showed similarity\nbetween the three different treatment groups. The adverse event incidence was similar across treatment arms and\nthere were no unexpected safety events.Conclusions: Overall, these results show that the proposed pegfilgrastim biosimilar is similar to Amgenâ??s US-licensed\nand EU-approved pegfilgrastim reference products with regard to the clinical efficacy and safety endpoints assessed....
With the development of anti-human epidermal growth factor receptor 2 (HER2)\nmonoclonal antibodies, trastuzumab-based therapy has become the standard of care among patients\nwith early or advanced HER2-positive breast cancer. However, real-world data have shown that\nup to a half of patients do not receive trastuzumab or any other HER2-targeted agent, mainly due\nto high treatments costs. The prospect of a more enlarged access to trastuzumab treatment lies\nin the use of biosimilars, as the European and the US patent of the reference products has or will\nsoon expire. Biosimilars are biologics highly similar in terms of quality characteristics, biological\nactivity, safety and efficacy to already approved biologics. The biosimilarity of any European\nUnion (EU)-approved biosimilar is guaranteed based on the comprehensive comparability exercise\nwhich includes comparative analytical, non-clinical and clinical studies. In the matter of biosimilarsâ??\ninterchangeability and substitution, the European Medicines Agency (EMA) and US Food and\nDrug Administration (FDA) have adopted different positions, triggering various discussions on\nthe potential immunogenicity and efficacy in individual patients. As more biosimilars are gaining\napproval, the present review aims to offer concise information for oncologists and pharmacists about\nthe production, approval, interchangeability, and substitution policies of biosimilars used in breast\ncancer therapy, with a special focus on trastuzumab....
Objective: The aim was to critically evaluate well-established regulatory agencies mAb\nbiosimilar guidelines for development and marketing authorization about quality, efficacy\nand safety and compare to BRICS-TM regulations to identify challenges.\nMaterials and Methods: The current valid guidelines of EMA, WHO, USFDA,\nBGTD/HC, ICH, and BRICS-TM were obtained from official websites and comparative\nqualitative review was performed.\nResults: The review revealed that Health Canada uses mAb specific guidelines\nfrom EMA or USFDA when necessary. The BRICS agencies (except Russia) have\nincorporated some or most of the WHO SBP TRS and related annexes in similar\nnational biotechnological/biological guidelines; however, gaps or insufficient information\nhave been identified. The Russian Federation has issued general product registration\nguideline/s with very brief information about mAbs. The TMMDA (Turkey) has published\nan updated biosimilar guideline which parallels those of the EMA and the ones from WHO;\nhowever, no mAb specific guidelines are published. COFEPRIS (Mexico) has published a\nbiotechnological/biological product registration guideline with no information about mAb.\nThe SAHPRA biosimilar guideline has an annex on mAbs which focuses on non-clinical\nand clinical aspects.\nThe comparative evaluation of BRICS-TM agencies indicates a gap pertaining to\nclarification for physico-chemical characterization, manufacturing process, overages and\ncompatibility requirements between biological substances and excipients specifically on\nmAbs. In vitro assay requirements seem quite aligned with those of WHO, whereas in vivo\nstudies mostly have disparity in terms of necessity, type of studies as well as design and\ncriteria. Clinical safety and efficacy studies are indicated in emerging regulatory agencies,\nhowever detailed information pertaining to design, size of populations, requirements for\nprimary and secondary endpoints, clarity and evaluation criteria differ. In general, BRICSTM\nagencies allow extrapolation of indications provided that pre-defined conditions are\nmet. Interchangeability, switching and substitution of biosimilars are not defined in most of BRIC-TM guidelines whereas South Africa, by law, allows neither interchangeability\nnor substitution. Pediatric research remains questionable across BRICS-TM.\nConclusions: EMA, USFDA guidelines are broadly aligned with WHO and in addition,\nthey also contain specific requirements pertaining to their own region. BRICS-TM\nhas considerably less defined mAb specific biosimilar development and comparability\nparameters in their published guidelines....
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