Development of mathematical modelling tools for comparison of biosimilars

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Subsequent entry pharmaceutical (also known as off-patent or generic) drug manufacturing can providesignificant savings to patients and healthcare systems. To enter the market, a subsequent entry pharmaceuticaldrug must be demonstrated to be as therapeutically effective as the original patented version. Demonstrationsof equivalence are relatively straightforward for most traditional small-molecule drugs, as molecular replicas ofthe original can be readily generated by chemical synthesis. In contrast, demonstration of equivalence of thenew class of biologic drugs (such as therapeutic antibodies) is not possible because these drugs are producedfrom diverse biological sources (such as living cells) which results in considerable variability in their structure(and hence chemistry) during manufacturing, even between production batches. As a consequence, subsequententry biologics cannot be compared to the original patented biologic solely on the basis of structural andchemical features; and are therefore, often referred to as biosimilars rather than generics. The Canadianpharmaceutical company Apobiologix (Division of ApoPharma USA, Inc; a member of the Apotex Group ofCompanies) is exploring new approaches for verifying the similarity of its new subsequent entry biosimilar toa an the clinically approved breast-cancer biologic known as trastuzamab (marketed as Herceptin). They areseeking to characterize cellular responses of trastuzumab and their biosimilar to identify similarities anddifferences in drug action. As part of that characterization, the proposed research involves development of acomputational modelling framework to interpret data from experiments comparingthe effects of these drugs onbiochemical response networks in breast cancer cells. Insights from these modeling analyses are expected toreduce the time for development efforts of Apobiologix's trastuzamab biosimilar to reach the market, bringingcost-savings to breast cancer patients and healthcare systems earlier rather than later.