Replies to post #192506 on Biotech Values

[dewophile]

FGEN

I understand it's tough to handicap a large trial like this w many variables. Given this is essentially a safety trial it's fair to say the longer it goes the greater the odds of success, and i guess we can leave it at that. Overall event rates are high (even in non-dialysis where i found it to be in the 5% range), so if half of patients have already been enrolled with a critical mass getting close to 6 months exposure and no imbalance goign the wrong way i would get more comfortable..

And what, pray tell, are the places you'd expect greater 'safety' for Roxa? (-g-). (I am amused that there is a giant elephant in the room that no one mentions directly. And I am no different - but I'll at least open the dialog now.)

you answered your own question so i don't have much to add. I agree MACE is the most significant, and based on what we know i would think this could go in favor of roxa more than the other way around. Better correction of anemia can lower CHF, which is perhaps the single largest SAE noted in trials. If erythropoetin is linked to MACE directly then obviously that can favor roxa. Same goes for excursions above targeted HGB. HTN too looks like it should be lower w roxa. The improvement in lipids is likely something that won't affect MACE early on.

another major cause of death in CKD is infection and decreasing hepcidin may increase infection rate

good point

[mcbio]

FGEN -

a) another major cause of death in CKD is infection and decreasing hepcidin may increase infection rate.

Can you expand on this a bit? What is the rationale for decreasing hepcidin possibly increasing infection rate? Is there support in the literature for this?

I'd wager the MACE rate will benefit substantially from roxa in comparison to epo - and a good shot even against placebo because the iron cycle is probably significantly important to coag etc (and roxa seems to normalize that). But the rest is very much an unknown - except to the DSMB which will have seen at least trends by now.

So, what if there ends up being a benefit for roxa on MACE but clear negative trend on infection rate?

[biomaven0]

>>decreasing hepcidin may increase infection rate

I suppose that is possible, but at this point it is well established that high hepcidin levels are associated with higher mortality, both in CKD and HIV anemia. Now that is an association, not proof of causation, but it does make your claim that much less likely.

Here are a couple of references:

>Hepcidin-25 in Diabetic Chronic Kidney Disease Is Predictive for Mortality and Progression to End Stage Renal Disease
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4404250/


>Elevated Hepcidin Is Part of a Complex Relation That Links Mortality with Iron Homeostasis and Anemia in Men and Women with HIV Infection
http://jn.nutrition.org/content/early/2015/04/22/jn.114.203158.abstract