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After Recknor's clarification, I understand it a l

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Post# of 153807
(Total Views: 735)
Posted On: 06/09/2022 11:40:04 PM
Posted By: MGK_2
After Recknor's clarification, I understand it a little more.

Seems like the worse a patient is at the get go, the more of a profound negative change in liver scarring the patient would benefit from through weekly dosing with LL.

The real dramatic losses in cT1 were found when the baseline cT1 was >950 msec. Patient's lost on average 68.86 msec with 14 treatments of LL.

We have learned that an 88ms drop in cT1 was equivalent to a 2 point drop in NAS staging with 8 being the worst. >8 = cirrhosis. Therefore, a patient whose base line cT1 is say 1,000 msec has significant liver scarring and may have a NAS of 7 or 8. After 14 weeks of treatment with LL, he can expect to drop his NAS score down to a 5 or 6 and drop his cT1 baseline to 930. In 14 weeks, he went from NAS 7 to NAS of 5 and cT1 went from 1,000 to 930.

As the patient's baseline cT1 improves by becoming less and less, shorter and shorter, the amount of benefit he/she derives from continued Leronlimab treatment begins to quickly diminish. Even by the time his baseline is 825 ms, the benefit he derives, becomes more akin to a reduced rate of actual scarring, rather than a positive increase in the amount of scar tissue removed.

So patients with a baseline cT1 between 875 msec and 950 msec treated with LL, will still lose scar tissue, but at a much slower rate. It make take 4 consecutive or intermittent (14 week treatment series) to drop the NAS by only another 2 stages. Therefore, to drop 88 m sec in cT1, it could take 1 year of weekly leronlimab treatments. Here the patient went from NAS 5 to NAS 3 in 1 more year leaving him with a cT1 of 825 msec.

Since the majority of patients that have NASH and NAFLD will have baselines below 950ms, it will take significantly longer than 14 weeks of treatment to drop by 2 NAS points.

I think this small study will show that patients will need to be treated with LL for about a year to a year and a half to drive their NAS scores down to their physician's preference level.

It is obvious from the 2 charts that some patients responded better than others. So some patients may not need to remain on it as long and others may require longer dosing periods. How CCR5 is related to this can not be determined by the information given. Why 700mg dosing did not work as expected, I have not yet considered that.


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