Focused Solely on Fibrosis, The Prevalence Is Massive as-is the Potential
The results of the NASH trial show that the target patient population for 350mg LL are Patients with a Fibrosis Stage of 2 or higher . How easily are these patients identified? Quite easy.
From here: Clinical Care Pathway for the Risk Stratification and Management of Patients With Nonalcoholic Fatty Liver Disease - ScienceDirect
https://www.sciencedirect.com/science/article...8521033849
Hepatic fibrosis is the most important determinant of liver and non-liver outcomes in patients with NAFLD. Therefore, identifying patients with clinically significant hepatic fibrosis (fibrosis stage 2 or higher) is paramount.
We recommend that all individuals in the target risk groups undergo a 2-tier process to assess for clinically significant liver fibrosis . The first tier involves using simple, nonproprietary fibrosis scores.
The Pathway relies on the FIB-4 score because it has been shown to have the best diagnostic accuracy for advanced fibrosis compared with other noninvasive markers of fibrosis in patients with NAFLD. FIB-4 score also correlates with clinical outcomes in patients with NAFLD.
FIB-4 provides a useful, inexpensive , first-line assessment of liver fibrosis for use in primary care.
Calculating FIB-4 is simple and can be done with (2) very common blood tests, Complete Blood Count and Comprehensive Metabolic Panel. The parameters used in this test are the patient's age, AST, Platelet Count and ALT , where AST and ALT are liver enzymes found on the CMP. The Platelet count is on the CBC. It is found by multiplying patient's age by AST and dividing that quantity by (Platelet count * the square root of ALT) .
Patients with FIB-4 score >2.67 are at high risk for advanced fibrosis, with most studies reporting positive predictive values of 60%–80%
Patients with an FIB-4 test in the indeterminate range (ie, 1.3–2.67) should undergo LSM , which can be done as a point-of-care test in the primary care or endocrinology clinic, ordered by the clinician as other imaging tests to be reviewed at the next visit or as part of a referral to hepatology.
If the initial FIB-4 is in the indeterminate range, (1.3-2.67), then LSM, (Liver Stiffness Measurement) is required . To assess liver stiffness, the Pathway uses FibroScan, which is based on vibration controlled transient elastography (VCTE).
On VCTE, a value of >12.1 kPa indicates that clinically significant fibrosis is likely, with positive predictive values of 76% and 88% in patients seen in diabetes and hepatology clinic populations, respectively, A FIB-4 score >2.67 together with an LSM using VCTE ≥12.0 kPa is highly suggestive of advanced liver fibrosis. An LSM ≥20 kPa on VCTE or thrombocytopenia is highly suggestive of cirrhosis.
Fibroscan (Transient Elastography) for the Measurement of Liver Fibrosis - PMC (nih.gov)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3594956/
What is my FibroScan result and what does it mean? Results are measured using kiloPascal’s (or kPa) and range from 2 to 75. The normal range for a FibroScan is between 2 to 7 kPa. The average normal result is 5.3 kPa. Your liver doctor/NP will explain these results to find out how much scarring you have. Your result will vary based on what liver disease you have.
Scarring has 4 stages: • F0 means no scarring • F1 is mild fibrosis • F2 is moderate fibrosis • F3 is severe fibrosis • F4 is cirrhosis or advanced fibrosis
FibroScan® and Liver Disease (uhn.ca)
https://www.uhn.ca/PatientsFamilies/Health_in...isease.pdf
//
We know that of the 333 million individuals in the US population and/or 8 Billion world wide at least, (a very conservative estimate): 1/25 have NASH and 1/100 have Stage 4 Hepatic Fibrosis. Extrapolating:
For USA, at least 10,000,000 have NASH and at least 3 Million have Stage 4 Hepatic Fibrosis .
For World, at least 300,000,000 have NASH and at least 80,000,000 have Stage 4 Hepatic Fibrosis.
These are VERY conservative numbers.
//
For the potential NASH patients above, a 2 tier testing method should be sufficient to determine if leronlimab treatment would be indicated.
Obtain FIB-4; If FIB-4 > 2.67, then Patient has at least Fibrosis stage of 2 or higher and Leronlimab should be indicated
If FIB-4 < 1.3, Fibrosis stage is less than 2 and Leronlimab would not be indicated
If FIB-4 is between 1.3 and 2.67, this is indeterminant and a second tier is necessary.
For these individuals, obtain Liver Stiffness Measurement, Fibroscan. If VCTE > 12.0 kPa, with FIB-4 > 1.3, then these patients would have a Fibrosis Stage of 2 or higher and would be candidates for Leronlimab.
//
Very conservatively we know:
For USA, at least 10,000,000 have NASH and at least 3 Million have Stage 4 Hepatic Fibrosis.
We can apply the above tests to these patients and determine their FIB-4 and for some others obtain Fibroscan to identify those with Fibrosis Stage of at least 2.
Of these, let's say very conservatively, that only 1 million are found to be Fibrosis Stage 2 or greate r and are subsequently treated with 350mg Leronlimab weekly for only 8 weeks, just about 1/2 our trial.
8 weeks * 1,000,000 patients * $1,000 per vial = $8 billion annual for treating merely a very small proportion of the patient population out there and only treating them for 1/2 of 1 course.
The results of the NASH trial show that the target patient population for 350mg LL are Patients with a Fibrosis Stage of 2 or higher . How easily are these patients identified? Quite easy.
From here: Clinical Care Pathway for the Risk Stratification and Management of Patients With Nonalcoholic Fatty Liver Disease - ScienceDirect
https://www.sciencedirect.com/science/article...8521033849
Hepatic fibrosis is the most important determinant of liver and non-liver outcomes in patients with NAFLD. Therefore, identifying patients with clinically significant hepatic fibrosis (fibrosis stage 2 or higher) is paramount.
We recommend that all individuals in the target risk groups undergo a 2-tier process to assess for clinically significant liver fibrosis . The first tier involves using simple, nonproprietary fibrosis scores.
The Pathway relies on the FIB-4 score because it has been shown to have the best diagnostic accuracy for advanced fibrosis compared with other noninvasive markers of fibrosis in patients with NAFLD. FIB-4 score also correlates with clinical outcomes in patients with NAFLD.
FIB-4 provides a useful, inexpensive , first-line assessment of liver fibrosis for use in primary care.
Calculating FIB-4 is simple and can be done with (2) very common blood tests, Complete Blood Count and Comprehensive Metabolic Panel. The parameters used in this test are the patient's age, AST, Platelet Count and ALT , where AST and ALT are liver enzymes found on the CMP. The Platelet count is on the CBC. It is found by multiplying patient's age by AST and dividing that quantity by (Platelet count * the square root of ALT) .
Patients with FIB-4 score >2.67 are at high risk for advanced fibrosis, with most studies reporting positive predictive values of 60%–80%
Patients with an FIB-4 test in the indeterminate range (ie, 1.3–2.67) should undergo LSM , which can be done as a point-of-care test in the primary care or endocrinology clinic, ordered by the clinician as other imaging tests to be reviewed at the next visit or as part of a referral to hepatology.
If the initial FIB-4 is in the indeterminate range, (1.3-2.67), then LSM, (Liver Stiffness Measurement) is required . To assess liver stiffness, the Pathway uses FibroScan, which is based on vibration controlled transient elastography (VCTE).
On VCTE, a value of >12.1 kPa indicates that clinically significant fibrosis is likely, with positive predictive values of 76% and 88% in patients seen in diabetes and hepatology clinic populations, respectively, A FIB-4 score >2.67 together with an LSM using VCTE ≥12.0 kPa is highly suggestive of advanced liver fibrosis. An LSM ≥20 kPa on VCTE or thrombocytopenia is highly suggestive of cirrhosis.
Fibroscan (Transient Elastography) for the Measurement of Liver Fibrosis - PMC (nih.gov)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3594956/
What is my FibroScan result and what does it mean? Results are measured using kiloPascal’s (or kPa) and range from 2 to 75. The normal range for a FibroScan is between 2 to 7 kPa. The average normal result is 5.3 kPa. Your liver doctor/NP will explain these results to find out how much scarring you have. Your result will vary based on what liver disease you have.
Scarring has 4 stages: • F0 means no scarring • F1 is mild fibrosis • F2 is moderate fibrosis • F3 is severe fibrosis • F4 is cirrhosis or advanced fibrosis
FibroScan® and Liver Disease (uhn.ca)
https://www.uhn.ca/PatientsFamilies/Health_in...isease.pdf
//
We know that of the 333 million individuals in the US population and/or 8 Billion world wide at least, (a very conservative estimate): 1/25 have NASH and 1/100 have Stage 4 Hepatic Fibrosis. Extrapolating:
For USA, at least 10,000,000 have NASH and at least 3 Million have Stage 4 Hepatic Fibrosis .
For World, at least 300,000,000 have NASH and at least 80,000,000 have Stage 4 Hepatic Fibrosis.
These are VERY conservative numbers.
//
For the potential NASH patients above, a 2 tier testing method should be sufficient to determine if leronlimab treatment would be indicated.
Obtain FIB-4; If FIB-4 > 2.67, then Patient has at least Fibrosis stage of 2 or higher and Leronlimab should be indicated
If FIB-4 < 1.3, Fibrosis stage is less than 2 and Leronlimab would not be indicated
If FIB-4 is between 1.3 and 2.67, this is indeterminant and a second tier is necessary.
For these individuals, obtain Liver Stiffness Measurement, Fibroscan. If VCTE > 12.0 kPa, with FIB-4 > 1.3, then these patients would have a Fibrosis Stage of 2 or higher and would be candidates for Leronlimab.
//
Very conservatively we know:
For USA, at least 10,000,000 have NASH and at least 3 Million have Stage 4 Hepatic Fibrosis.
We can apply the above tests to these patients and determine their FIB-4 and for some others obtain Fibroscan to identify those with Fibrosis Stage of at least 2.
Of these, let's say very conservatively, that only 1 million are found to be Fibrosis Stage 2 or greate r and are subsequently treated with 350mg Leronlimab weekly for only 8 weeks, just about 1/2 our trial.
8 weeks * 1,000,000 patients * $1,000 per vial = $8 billion annual for treating merely a very small proportion of the patient population out there and only treating them for 1/2 of 1 course.
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