Here is another way to look at it. Certainly, the LL 350mg dose is effective at removing scar tissue. However, the more a person has, the better it is at removing it, and sort of the opposite of that is true. The less a person has, it is not as effective as removing it, but instead, may only allow the scar tissue from continuing to build up, but at a far slower rate than had LL not been given.
In the Placebo group, the cT1 increased by 27.64msec in 14 weeks. That means that on average, patients without medication formed 27.64 scar tissue in 14 weeks. So without medication, the tendency was to increase scar tissue.
We do not know from this abstract what the "Baseline cT1" was of the Placebo group. All we know, is that to be entered into the study, the baseline cT1 had to be greater than 800 msec.
Our best results came from treatment with 350mg LL weekly and the best results came in the Baseline cT1 > 950 msec patients. These patients had a level of fibro-inflammation considered Severe. Here, NAS scores are 7 or 8, if not cirrhotic. In these 7 individuals, treatment with 350mg LL for 14 weeks removed 68.86 msec fibrotic scar tissue from liver. While in the Placebo patient with their cT1 baseline unknown, they were more likely to add more scar tissue.
We know that each 88 msec drop in cT1 represents a reduction in NAS by 2 stages. So in severely fibrotic patients, a 14 week stent of weekly Leronlimab can take a patient from a NAS of 8 to a NAS of 6. Another way of stating, early Cirrhosis to early NASH or yet another way of stating, Severe NASH to Severe NAFLD. Scar tissue has been removed from around the liver yielding a significant reduction in cT1. Let's say our patient originally started out with a cT1 of 1010 and after 14 weeks of LL, ended up with a cT1 of 940. taking him from a NAS of 8 to NAS of 6.
Now the patient's baseline has improved. But the effectiveness of leronlimab has become less. In the 350mg subgroup with cT1 baselines between 875 msec and 950 msec, the average rate of fibrosis removal was 42.0 msec per 14 week trial of leronlimab. For patients in this moderate to severe sub-group of fibro-inflammation, it would require (2) courses of the 14 week LL series to achieve a reduction of (2) NAS stages which was nearly achieved in only (1) 14 week course of LL in the Severely fibrotically inflammed subgroup.
So taking a patient in this Moderate to Severe subgroup with a cT1 of 942, after the 1st 14 week course, the patient would have lost 42 msec in cT1 and have a cT1 of 900 but would remain in the same Moderate to Severe subgroup. His NAS stage would have been reduced by 1. Doing a second 14 week course of LL, he would have lost another 42 msec in cT1 giving him a cT1 of 860 leaving him yet still in the same subgroup, but with another 1 stage downgrade in his NAS score. So, our patient improved from cT1 of 1010 to 942, loses 42 in the next 14 week course giving him cT1 of 900 and improves 1 stage in NAS giving him NAS of 5. He undergoes yet another 14 week stent of LL giving him a cT1 of 860 msec and improving his NAS by yet another stage leaving him with NAS of 4.
At this point, our patient is below the 875 msec threshold, where the classification would be Mild fibro-inflammation, where the effectiveness of LL to actually remove fibrotic scar tissue is cut in half again to only 24.38 msec and may even begin to show signs of only halting or slowing the progression of fibrotic scarring instead of signs of removal of scar tissue. By giving another 14 week course of LL, we can realistically only expect to appreciate a reduction of another 25 msec of cT1 which would take our patient from 860 to a cT1 of 835. NAS score would likely not change or at best be improved to NAS of 3. However, a NAS of 3 is considered a light stage of NAFLD.
In these patient's in the Mild fibrosis range, it may be decided to use LL on a maintenance dose to prevent the fibrosis from progression. It may be used to hold patients at a lower NAS stage, rather than to allow them to progress into deeper stages of NAFLD or even into NASH.
So in this example, I've shown how LL could bring a nearly cirrhotic patient with a baseline cT1 of 1010 and NAS of 8, down to a low grade NAFLD with a cT1 of 835 and a NAS of 3 with (4) 14 week courses of weekly LL. That's about a year of weekly leronlimab, on average, should be able to accomplish what I've outlined here.
In addition, LL may then be possibly prescribed once every 2 weeks or every month, as a maintenance dose to prevent the progression of NAFLD into full blown NASH and to maintain the patient at lower NAS stages. The patient may be held in this low level NAFLD stage indefinitely without the progressing scarring fibrosis which would other wise result had the patient not received this maintenance therapy.
Yes, LL 350mg is definitely a medication for Cirrhosis, Severe, Moderate, Mild NASH and even as maintenance therapy for NAFLD. Good News Folks.
In the Placebo group, the cT1 increased by 27.64msec in 14 weeks. That means that on average, patients without medication formed 27.64 scar tissue in 14 weeks. So without medication, the tendency was to increase scar tissue.
We do not know from this abstract what the "Baseline cT1" was of the Placebo group. All we know, is that to be entered into the study, the baseline cT1 had to be greater than 800 msec.
Our best results came from treatment with 350mg LL weekly and the best results came in the Baseline cT1 > 950 msec patients. These patients had a level of fibro-inflammation considered Severe. Here, NAS scores are 7 or 8, if not cirrhotic. In these 7 individuals, treatment with 350mg LL for 14 weeks removed 68.86 msec fibrotic scar tissue from liver. While in the Placebo patient with their cT1 baseline unknown, they were more likely to add more scar tissue.
We know that each 88 msec drop in cT1 represents a reduction in NAS by 2 stages. So in severely fibrotic patients, a 14 week stent of weekly Leronlimab can take a patient from a NAS of 8 to a NAS of 6. Another way of stating, early Cirrhosis to early NASH or yet another way of stating, Severe NASH to Severe NAFLD. Scar tissue has been removed from around the liver yielding a significant reduction in cT1. Let's say our patient originally started out with a cT1 of 1010 and after 14 weeks of LL, ended up with a cT1 of 940. taking him from a NAS of 8 to NAS of 6.
Now the patient's baseline has improved. But the effectiveness of leronlimab has become less. In the 350mg subgroup with cT1 baselines between 875 msec and 950 msec, the average rate of fibrosis removal was 42.0 msec per 14 week trial of leronlimab. For patients in this moderate to severe sub-group of fibro-inflammation, it would require (2) courses of the 14 week LL series to achieve a reduction of (2) NAS stages which was nearly achieved in only (1) 14 week course of LL in the Severely fibrotically inflammed subgroup.
So taking a patient in this Moderate to Severe subgroup with a cT1 of 942, after the 1st 14 week course, the patient would have lost 42 msec in cT1 and have a cT1 of 900 but would remain in the same Moderate to Severe subgroup. His NAS stage would have been reduced by 1. Doing a second 14 week course of LL, he would have lost another 42 msec in cT1 giving him a cT1 of 860 leaving him yet still in the same subgroup, but with another 1 stage downgrade in his NAS score. So, our patient improved from cT1 of 1010 to 942, loses 42 in the next 14 week course giving him cT1 of 900 and improves 1 stage in NAS giving him NAS of 5. He undergoes yet another 14 week stent of LL giving him a cT1 of 860 msec and improving his NAS by yet another stage leaving him with NAS of 4.
At this point, our patient is below the 875 msec threshold, where the classification would be Mild fibro-inflammation, where the effectiveness of LL to actually remove fibrotic scar tissue is cut in half again to only 24.38 msec and may even begin to show signs of only halting or slowing the progression of fibrotic scarring instead of signs of removal of scar tissue. By giving another 14 week course of LL, we can realistically only expect to appreciate a reduction of another 25 msec of cT1 which would take our patient from 860 to a cT1 of 835. NAS score would likely not change or at best be improved to NAS of 3. However, a NAS of 3 is considered a light stage of NAFLD.
In these patient's in the Mild fibrosis range, it may be decided to use LL on a maintenance dose to prevent the fibrosis from progression. It may be used to hold patients at a lower NAS stage, rather than to allow them to progress into deeper stages of NAFLD or even into NASH.
So in this example, I've shown how LL could bring a nearly cirrhotic patient with a baseline cT1 of 1010 and NAS of 8, down to a low grade NAFLD with a cT1 of 835 and a NAS of 3 with (4) 14 week courses of weekly LL. That's about a year of weekly leronlimab, on average, should be able to accomplish what I've outlined here.
In addition, LL may then be possibly prescribed once every 2 weeks or every month, as a maintenance dose to prevent the progression of NAFLD into full blown NASH and to maintain the patient at lower NAS stages. The patient may be held in this low level NAFLD stage indefinitely without the progressing scarring fibrosis which would other wise result had the patient not received this maintenance therapy.
Yes, LL 350mg is definitely a medication for Cirrhosis, Severe, Moderate, Mild NASH and even as maintenance therapy for NAFLD. Good News Folks.
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