Approval of the first Car-T therapy, Novartiss Kymriah, brought with it a concomitant green light for Roches rheumatoid arthritis drug Actemra for treating cytokine release syndrome (CRS), a frequent side effect of Car-T. Now Jazz Pharmaceuticals wants in on the act, starting a 35-subject study of its drug Defitelio to treat the side effect of neurotoxicity associated with Gileads Car-T therapy Yescarta. Defitelio is approved for treating a rare complication of stem cell transplantation, and the thinking is that its mechanism of cathepsin G inhibition could help prevent endothelial cell damage, protecting the CNS and minimising neurotoxicity. Little is known about why some Car-T patients experience neurotoxicity, but this is thought to be related to CRS. The logic behind Actemras useis that the drug blocks IL-6, one of the most highly elevated cytokines in CRS. Advantages for Defitelio could be arguable safety while its label cites haemorrhage risk it does not have Actemras boxed warning over infections and slightly longer patent life. Still, as Defitelio is a small molecule it might end up being genericised before the US sees biosimilar versions of Actemra.

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Jazz plays itself into cell therapy - Vantage