Quote:Gilead had carefully gathered a battery of safety data in making their pitch, drawing on a range of studies. The FDA has been acutely concerned about the JAK class of anti-inflammatories, running from restrictions on Pfizer’s JAK1/JAK3 inhibitor Xeljanz’s use to an initial rejection for Eli Lilly’s Olumiant.
One of the problem with single target immune inhibitors is that at larger doses where they would be most effective they could shut down the action of the target completely which could have negative effects. Those effects of completely stopping a component of the immune response can rise to the level of increased incidence of lymphoma and leukemia.
My theory of how leronlimab works as immunomodulator is by blocking the largest target of immune/inflammatory response CCR5. The other CCR receptors which also bind the same ligands which would be overexpressed end up picking up the slack and producing a normal level of immune response.
Leronlimab also inhibits JAK1, JAK2 and JAK3. Under my theory blocking CCR5 cuts out the JAK expression caused by it but the other receptors maintain a normal level with no degradation of normal immune operation.
Going back to the inventor of leronlimab it has been claimed leronlimab acts as an immunomodulator by allowing ligand binding but blocking HIV. The company claims it to this day. Which of course is completely wrong. If leronlimab had normal ligand binding then there would be no effect on an overexpressed immune system or inflammation. Also all CCL ligands that bind to CCR5 bind to the n terminus which leronlimab binds to and which would stop those ligands from binding.
One of the problems with the FDA may be that the mechanism claimed for leronlimab's immunomodulation capabilities makes little sense and the FDA sees it as an immune suppressor. It could be one of the reasons why the FDA said only 2 doses for CD12. Testing for my theory would be fairly straightforward and relatively cheap and should be done.
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