The third generation of TPO mimetics are again biologics
After failure of 1st generation thrombopoietic growth factors due to immunogencity, the 2nd generation is focused on oral TPO mimetics, now followed by a 3rd generation of engineered biologics with potential for higher potency and efficacy
The Business Intelligence firm La Merie S.L. reported in its most recent pipeline update of thrombopoiesis stimulating agents that eight thrombopoietin (TPO) mimetics are in clinical stages of development. The two most advanced are close to FDA's decision on the marketing application. Due to immunogenicity problems, TPO and pegylated TPO developments were abandoned, except one product approved in China. Second generation molecules reduced the immunogenicity problem by genetic engineering and by discovery of small molecule thrombopoietin receptor agonists with the additional advantage of oral drug delivery. At least five oral TPO agonists are in clinical development and one further compound is soon to follow. A third generation of thrombopoiesis stimulating agents consists of biologics generated by genetic engineering of existing growth factors, fusion of known and new growth factors or antibodies directed against new targets on megakaryocytes. Although most of the 3rd generation molecules are still in preclinical R&D, first data indicate the potential for higher potency. These results and more were found in a search conducted by La Merie Business Intelligence.
The report provides information on competitor projects in development as novel thrombopoiesis stimulating agents for treatment of idiopathic thrombocytopenic purpura (ITP) or prevention of severe thrombocytopenia and reduction of the need for platelet transfusion in patients undergoing chemotherapy. Two products are approved for treatment or prevention of thrombocytopenia.
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