When Gilead Sciences announced its $21 billion acquisition of Immunomedics one week ago, Gilead executives said that clinical data on Immunomedics’ cancer drug Trodelvy — shared confidentially during negotiations — justified the high cost of the deal.

On Saturday, data from Trodelvy studies in bladder cancer and triple-negative breast cancer were presented publicly for the first time at the annual meeting of the European Society for Medical Oncology.

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  • Both Trodelvy (Sactuzumab Govitecan) and Padcev (Enfortumab Vedotin) are trojan horse drugs, known more commonly as antibody-drug-conjugates. The antibody delivers the chemotherapy drug to very close proximity to the tumor cells, maximizing anti-tumor effect and minimizing side effects. Although most of the drug is delivered “to the tumor”, some escapes, so-to-speak and causes side effects, mostly gi (diarhea) and myelosuppession (low white blood count, et al). The “tecan” refers to SN-38, the basic topoisomerase II inhibitor and the main player in the drugs Topotecan and Irinotecan. Vedotin refers to a very potent mitotic spindle inhibitor for which there is no similar iv drug. Different mechanisms of action. The question I have, is “is there any synergism in-vitro between the tecans and vedotin?” Because if there is, one might ask… “shouldn’t these drugs be tested as combination.” Not full doses, mind you. But start with a half dose of both. It is conceivable that the combination might be highly effective. Keep in mind, if the synergism is limited to high concentrations, you could effect a tremendous anticancer action at the site of the tumor and negligible toxicity since at the site of the marrow and gi tract the concentrations would be low. So… what are the chances that such a combination would reach the clinic? Not a chance in hell. This sort of thinking is something that the pharmaceutical industry is incapable of. And that goes for the FDA, the NCI and any thought leaders in oncology. It is a shame but that is pretty much how it is. They might be missing out in a tremendously effective treatment, but studying it will never happen.

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